Becky McCall

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

A version of this article first appeared on Medscape.com.

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

A version of this article first appeared on Medscape.com.

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

A version of this article first appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.

At the annual European Congress of Rheumatology, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.

“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Dr. Wagenaar reported.

“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.

In the patients with OA, Dr. Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
 

Significant Improvement in OA Pain, Stiffness, Physical Function

In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.

“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Dr. Wagenaar.

The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Dr. Wagenaar.

The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.

Participants were encouraged to try to avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Dr. Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.

Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m². A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.

In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P < .0001) compared with the start of the PFJ intervention.

“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Dr. Wagenaar.

She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m²), and waist circumference (from 110 to 106.7 cm).

By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.

Regarding medications use, Dr. Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
 

Disease Activity Improvement and Medication Reduction in RA

Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.

Dr. Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”

Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.

Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.

Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m², and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.

During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P < .0001).

“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Dr. Wagenaar.

Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.

A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.

Dr. Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.

In an interview, Dr. Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
 

Mechanisms Underpinning PFJ

Dr. Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.

“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.

Dr. Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.

“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”

They did not identify any change in calprotectin, an inflammation marker, but Dr. Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”

The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.

Fernando Estevez-Lopez, PhD, a sports scientist at Harvard T.H. Chan School of Public Health, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.

“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”

Dr. Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Dr. Estevez-Lopez reported having no relevant disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

VIENNA — Pneumococcal vaccination administered 1 month prior to starting methotrexate (MTX) in patients with rheumatoid arthritis (RA) allows a significantly higher immunological response at 1 month and does not affect disease control at 1 year, compared with starting MTX simultaneously with the vaccination, according to data from a randomized trial presented at the annual European Congress of Rheumatology.

“Our patients are more susceptible to infection due to immunosuppressive therapy, and it’s recommended they receive vaccination against pneumococcal infection,” the lead author Jacques Morel, MD, PhD, said in his presentation of results from the VACIMRA study.

Timing the vaccination against pneumococcal disease when initiating MTX in clinical practice has been a point of uncertainty, noted Dr. Morel, a rheumatologist from Centre Hospitalier Universitaire, Montpellier, France.

“How can we deal with this in clinical practice where one recommendation is to vaccine before initiation of methotrexate, but it is also recommended to start methotrexate as soon as the diagnosis of RA is made?” he asked.
 

Comparing Humoral Response of MTX Started Immediately or 1 Month Post-Vaccination

The prospective, randomized, multicenter trial aimed to compare the rate of humoral immunological response against pneumococcal 13-valent conjugate vaccine (PCV13) in patients with RA who had a Disease Activity Score in 28 joints (DAS28) > 3.2, never taken MTX, and never been vaccinated against pneumococcus. Patients were vaccinated either 1 month before MTX initiation (n = 126) or simultaneously with MTX (n = 123). Oral glucocorticoids were allowed but only at < 10 mg/d. Following PCV13 vaccination, all patients also received the 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later.

Concentrations of immunoglobulin (Ig) G antibodies against the 13 serotypes contained within PCV13 were measured using enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA) at baseline and during follow-up at 1, 3, 6, and 12 months.

Positive antibody response was defined as a twofold or more increase in the IgG concentration using ELISA. The main outcome was the responder rates at 1 month after PCV13, defined by at least three positive antibody responses out of five of the target PVC13 serotypes (1, 3, 5, 7F, and 19A) using ELISA or OPA. Secondary outcomes included comparisons of the percentage of patients responding to each of the 13 vaccine serotypes at 1 month and after the boost with PPV23 and at 3, 6, and 12 months after vaccination with PCV13. The researchers also measured disease activity, infections, and side effects throughout the study.

Dr. Morel highlighted that all the patients had very early RA of less than 6 months, and that their characteristics at baseline were similar in both groups with 70% women, mean age 55.6 years, RA duration 2 months, 69% positive for anticitrullinated protein antibodies, 21% with erosive disease, and a DAS28 based on C-reactive protein of 4.6.

Response rates in those receiving MTX 1 month after vaccination were significantly higher at 88% with ELISA than those at 75% for immediate vaccination (P < .01) and 96% vs 88% with OPA (P = .02). These responder proportions persisted at the 12-month follow-up measurements, remaining higher in the delayed MTX group for both assays and across the 13 serotypes.

Showing a graph of the antibody responses, Dr. Morel explained that “at 12 months, the curves start to converge, but the difference in antibody titers were still significant for eight of the 13 serotypes.”
 

Disease Activity Not Adversely Affected by Starting MTX 1 Month Later

Regarding medication doses at 12 months, the cumulative glucocorticoid doses were similar between groups during the follow-up. As expected, the 1-year cumulative dose of MTX was higher in those given the drug immediately after vaccination vs delayed (826 vs 734 mg), but the weekly mean doses of MTX were similar at 3, 6, and 12 months between the two groups, and likewise, the use of targeted disease-modifying antirheumatic drugs (DMARDs) at 1 year was comparable. The cumulative glucocorticoid dose at 12 months was similar at 1716 mg with delayed MTX and 1613 mg with immediate MTX.

Not unexpectedly, at 1 month, DAS28 scores were higher with delayed vs immediate MTX at 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (P < .01), but after the first month, DAS28 scores were similar between the two groups.

No significant differences were found between the groups for adverse event rates within 7 days of receiving PCV13, with local and systemic reactions occurring at 60%-61% and 50%-58%, respectively; fever at 0%-4%; and severe infections at 12%.

Finally, no difference was found in terms of serious adverse events between groups, with one pneumococcal infection with delayed MTX during follow-up, and there were no unexpected side effects observed with the PCV13 and PPV23 vaccinations.
 

Rheumatologists’ Reactions

Ernest Choy, MD, head of rheumatology and translational research at the Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, asked if any individual showed no humoral response at all rather than a reduced response. “I ask because if there is no humoral response, then they are at very high risk, and there will be clinical relevance to that.”

Dr. Morel replied that “one serotype showed no response, at least according to the assays used, but we don’t know why. We analyzed at the population [level], not at the individual level, so it is difficult to answer the question.”

Another delegate asked what the participants thought about delaying MTX by 1 month. “When we tell the patient we need to vaccinate before we can use methotrexate [because] otherwise, we will reduce the response to the vaccination, then patient accepts it,” said Dr. Morel, adding that, “we allowed a minimal dose of steroids, and we saw from the results that the DAS28 at 1 month had changed.”

Co-moderator Katerina Chatzidionysiou, MD, PhD, a consultant rheumatologist and head of the Clinical Trial Department Rheumatology Unit, Karolinska University Hospital, Stockholm, Sweden, said that “As a physician, I’d feel uncomfortable delaying MTX if they had very active disease even for a short period of time.”

Dr. Morel replied that, “Today, we have so many drugs that can control the disease, for example, the targeted DMARDs. Progression does not show much variation, and we know x-ray progression with today’s drugs is a lot less than previously.”

Dr. Morel reported financial relationships with AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, GlaxoSmithKline, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sandoz, Sanofi, Boehringer Ingelheim, and Servier. Dr. Choy had no relevant financial relationships of relevance to this study.

A version of this article appeared on Medscape.com.

TOPLINE: 

The intelligent Liver Function Testing (iLFT) platform can improve diagnosis and management of chronic liver disease in a primary care setting, new data show. 

METHODOLOGY:

• At the European Association for the Study of the Liver (EASL) Congress 2024, researchers presented 5-year, real-world data of the iLFT platform from its use in NHS Tayside in Dundee, Scotland, which serves a population of 400,000. The platform has been available since 2018.
• The iLFT platform uses an automated algorithm that analyzes standard liver function test results.
• Abnormal results prompt the system to initiate further fibrosis scoring and relevant etiologic testing to determine the cause of liver dysfunction.
• The results of these tests combined with practitioner-entered clinical information produce a probable diagnosis and recommend a patient-management strategy.

TAKEAWAY: 

• Of the 26,459 iLFT tests performed between 2018 and 2023, 68.3% (18,079) required further testing beyond the initial liver function test, whereas 31.7% (8380) did not.
• Further testing generated 20,895 outcomes, of which, isolated abnormal alanine transaminase (ALT) without fibrosis was most frequent (23.7%). Abnormal ALT was found to be most likely due to metabolic dysfunction–associated steatotic liver disease (MASLD).
• Overall, half of cascaded samples had a positive etiologic diagnosis. Alcoholic liver disease (ALD) and MASLD were the most common etiologic outcomes identified.
• In addition, 20% of cascaded tests identified potentially significant liver fibrosis.
• A total of 69.9% of outcomes recommended that patients could be safely managed in primary care. The inclusion of automatic Enhanced Liver Fibrosis (ELF) testing in 2020 further reduced the requirement for referral to secondary care by 34%.

IN PRACTICE:

“Without this algorithm, the 18,000 patients who had algorithm-directed further testing would have had to go back to the [primary care practitioner] to obtain the additional tests, and the [primary care practitioner] would need to interpret them too,” said Damien Leith, MD, trainee hepatologist at Ninewells Hospital, Dundee, Scotland, who presented the findings. “iLFTs ensure the right patients get automated, appropriate follow-up testing and subsequent recommendation of referral to secondary care if necessary, and importantly iLFT helps the primary care practitioner identify the cause of chronic liver disease.” 

SOURCE:

This study was presented on June 6, 2024 at the EASL Congress 2024 (abstract OS-007-YI).

LIMITATIONS:

Limitations include the need for further refinement of the algorithm to increase the proportion of positive etiologic iLFT outcomes. More analysis is needed to optimize the cost-effectiveness of iLFT. 

DISCLOSURES:

Dr. Leith reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

The intelligent Liver Function Testing (iLFT) platform can improve diagnosis and management of chronic liver disease in a primary care setting, new data show. 

METHODOLOGY:

• At the European Association for the Study of the Liver (EASL) Congress 2024, researchers presented 5-year, real-world data of the iLFT platform from its use in NHS Tayside in Dundee, Scotland, which serves a population of 400,000. The platform has been available since 2018.
• The iLFT platform uses an automated algorithm that analyzes standard liver function test results.
• Abnormal results prompt the system to initiate further fibrosis scoring and relevant etiologic testing to determine the cause of liver dysfunction.
• The results of these tests combined with practitioner-entered clinical information produce a probable diagnosis and recommend a patient-management strategy.

TAKEAWAY: 

• Of the 26,459 iLFT tests performed between 2018 and 2023, 68.3% (18,079) required further testing beyond the initial liver function test, whereas 31.7% (8380) did not.
• Further testing generated 20,895 outcomes, of which, isolated abnormal alanine transaminase (ALT) without fibrosis was most frequent (23.7%). Abnormal ALT was found to be most likely due to metabolic dysfunction–associated steatotic liver disease (MASLD).
• Overall, half of cascaded samples had a positive etiologic diagnosis. Alcoholic liver disease (ALD) and MASLD were the most common etiologic outcomes identified.
• In addition, 20% of cascaded tests identified potentially significant liver fibrosis.
• A total of 69.9% of outcomes recommended that patients could be safely managed in primary care. The inclusion of automatic Enhanced Liver Fibrosis (ELF) testing in 2020 further reduced the requirement for referral to secondary care by 34%.

IN PRACTICE:

“Without this algorithm, the 18,000 patients who had algorithm-directed further testing would have had to go back to the [primary care practitioner] to obtain the additional tests, and the [primary care practitioner] would need to interpret them too,” said Damien Leith, MD, trainee hepatologist at Ninewells Hospital, Dundee, Scotland, who presented the findings. “iLFTs ensure the right patients get automated, appropriate follow-up testing and subsequent recommendation of referral to secondary care if necessary, and importantly iLFT helps the primary care practitioner identify the cause of chronic liver disease.” 

SOURCE:

This study was presented on June 6, 2024 at the EASL Congress 2024 (abstract OS-007-YI).

LIMITATIONS:

Limitations include the need for further refinement of the algorithm to increase the proportion of positive etiologic iLFT outcomes. More analysis is needed to optimize the cost-effectiveness of iLFT. 

DISCLOSURES:

Dr. Leith reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE: 

The intelligent Liver Function Testing (iLFT) platform can improve diagnosis and management of chronic liver disease in a primary care setting, new data show. 

METHODOLOGY:

• At the European Association for the Study of the Liver (EASL) Congress 2024, researchers presented 5-year, real-world data of the iLFT platform from its use in NHS Tayside in Dundee, Scotland, which serves a population of 400,000. The platform has been available since 2018.
• The iLFT platform uses an automated algorithm that analyzes standard liver function test results.
• Abnormal results prompt the system to initiate further fibrosis scoring and relevant etiologic testing to determine the cause of liver dysfunction.
• The results of these tests combined with practitioner-entered clinical information produce a probable diagnosis and recommend a patient-management strategy.

TAKEAWAY: 

• Of the 26,459 iLFT tests performed between 2018 and 2023, 68.3% (18,079) required further testing beyond the initial liver function test, whereas 31.7% (8380) did not.
• Further testing generated 20,895 outcomes, of which, isolated abnormal alanine transaminase (ALT) without fibrosis was most frequent (23.7%). Abnormal ALT was found to be most likely due to metabolic dysfunction–associated steatotic liver disease (MASLD).
• Overall, half of cascaded samples had a positive etiologic diagnosis. Alcoholic liver disease (ALD) and MASLD were the most common etiologic outcomes identified.
• In addition, 20% of cascaded tests identified potentially significant liver fibrosis.
• A total of 69.9% of outcomes recommended that patients could be safely managed in primary care. The inclusion of automatic Enhanced Liver Fibrosis (ELF) testing in 2020 further reduced the requirement for referral to secondary care by 34%.

IN PRACTICE:

“Without this algorithm, the 18,000 patients who had algorithm-directed further testing would have had to go back to the [primary care practitioner] to obtain the additional tests, and the [primary care practitioner] would need to interpret them too,” said Damien Leith, MD, trainee hepatologist at Ninewells Hospital, Dundee, Scotland, who presented the findings. “iLFTs ensure the right patients get automated, appropriate follow-up testing and subsequent recommendation of referral to secondary care if necessary, and importantly iLFT helps the primary care practitioner identify the cause of chronic liver disease.” 

SOURCE:

This study was presented on June 6, 2024 at the EASL Congress 2024 (abstract OS-007-YI).

LIMITATIONS:

Limitations include the need for further refinement of the algorithm to increase the proportion of positive etiologic iLFT outcomes. More analysis is needed to optimize the cost-effectiveness of iLFT. 

DISCLOSURES:

Dr. Leith reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

MILAN — Fecal microbiota transplantation (FMT), also known as intestinal microbiota transplantation, significantly reduced recurrence of hepatic encephalopathy, compared with placebo, in patients with cirrhosis on standard-of-care treatment, results of a phase 2 randomized controlled trial show. 

“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.

Bajaj_Jasmohan_S_RICHMOND_web.jpg

Resetting the Gut

The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior. 

Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded. 

Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4). 

The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart. 

Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care. 

“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”

Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
 

One Dose of FMT Better Than None

Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%). 

SIP total/physical and psych scores improved with FMT (P = .003).

When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence. 

Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups. 

“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.

Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT. 

“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”

He pointed out that in smaller prior studies, the effects lasted up to 1 year. 
 

Setting the Stage for Phase 3 Trials

Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy. 

“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.

Kelly_Colleen_WEB.jpg

A version of this article appeared on Medscape.com.

MILAN — Fecal microbiota transplantation (FMT), also known as intestinal microbiota transplantation, significantly reduced recurrence of hepatic encephalopathy, compared with placebo, in patients with cirrhosis on standard-of-care treatment, results of a phase 2 randomized controlled trial show. 

“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.

Bajaj_Jasmohan_S_RICHMOND_web.jpg

Resetting the Gut

The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior. 

Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded. 

Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4). 

The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart. 

Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care. 

“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”

Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
 

One Dose of FMT Better Than None

Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%). 

SIP total/physical and psych scores improved with FMT (P = .003).

When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence. 

Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups. 

“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.

Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT. 

“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”

He pointed out that in smaller prior studies, the effects lasted up to 1 year. 
 

Setting the Stage for Phase 3 Trials

Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy. 

“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.

Kelly_Colleen_WEB.jpg

A version of this article appeared on Medscape.com.

MILAN — Fecal microbiota transplantation (FMT), also known as intestinal microbiota transplantation, significantly reduced recurrence of hepatic encephalopathy, compared with placebo, in patients with cirrhosis on standard-of-care treatment, results of a phase 2 randomized controlled trial show. 

“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.

Bajaj_Jasmohan_S_RICHMOND_web.jpg

Resetting the Gut

The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior. 

Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded. 

Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4). 

The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart. 

Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care. 

“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”

Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
 

One Dose of FMT Better Than None

Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%). 

SIP total/physical and psych scores improved with FMT (P = .003).

When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence. 

Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups. 

“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.

Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT. 

“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”

He pointed out that in smaller prior studies, the effects lasted up to 1 year. 
 

Setting the Stage for Phase 3 Trials

Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy. 

“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.

Kelly_Colleen_WEB.jpg

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Streptococcus pneumoniae, the bacteria that causes pneumococcal disease, is sixfold more likely to colonize adults older than 60 years who have regular contact with children than those who do not, data from a community-based study showed.

However, there is “no clear evidence of adult-to-adult transmission,” and the researchers, led by Anne L. Wyllie, PhD, from the Yale School of Public Health, New Haven, Connecticut, noted that the study results suggest “the main benefit of adult pneumococcal conjugate vaccine (PCV) immunization is to directly protect adults who are exposed to children, who still carry and transmit some vaccine-type pneumococci despite successful pediatric national immunization programs.”

The data show that relatively high pneumococcus carriage rates are seen in people who have regular contact with children, who have had contact in the previous 2 weeks, and who have had contact for extended periods, Dr. Wyllie explained.

Preschoolers in particular were found to be most likely to transmit pneumococcus to older adults. “It is the 24- to 59-month-olds who are most associated with pneumococcal carriage, more than 1- to 2-year-olds,” she reported. However, transmission rates from children younger than 1 year are higher than those from children aged 1-2 years, she added.

The findings were presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 global conference, formerly known as the ECCMID conference.
 

Originally Designed to Investigate Adult-to-Adult Transmission

The researchers wanted to understand the sources and dynamics of transmission, as well as the risk factors for pneumococcal disease in older adults, to help predict the effect of PCVs in people older than 60 years.

Although “we designed the study to specifically look at transmission between adults, in the end, we were presented with a very unique scenario” — restricted social mixing as a result of the COVID pandemic — during which “no community activities were happening,” Dr. Wyllie said. Because of this, the team was able to determine “the source of acquisition or transmission to the older adults was, very likely, coming from contact with children.”

Pneumococci are commonly found in respiratory tracts of healthy people. The US Centers for Disease Control and Prevention estimated that 20%-60% of school-aged children may be colonized compared with only 5%-10% of adults without children.

The longitudinal study was conducted among household pairs, such as married couples who were both aged at least 60 years and who did not have people younger than 60 years living in the household, in New Haven over two winter seasons: 2020-2021 and 2021-2022.

Self-collected saliva samples were assessed, and surveys on social behaviors and health were completed every 2 weeks for a 10-week period (with six study visits). The saliva sampling method was used because the researchers considered it to be more effective than samples from nasopharyngeal swabs. Quantitative polymerase chain reaction assays were used to test the saliva samples for the presence of pneumococcal DNA (pneumococcus genes piaB and lytA) and the diversity of pneumococcal strains (36 serotypes were targeted).
 

Strongly Suggestive of Transmission From Children to Older Adults

Of the 121 adults living in 61 households who were enrolled in the study, 62 adults participated in both seasons. Mean age was 70.9 years (range, 60-86 years), 51% of participants were women, and 85% were White.

Overall, 52 of 1088 (4.8%) samples tested positive for pneumococcus, and 27 of 121 (22.3%) adults were colonized on at least one sampling visit. Some were colonized at multiple timepoints, and two were colonized throughout the 10-week sampling period. Of the two participants who were colonized at five of six timepoints, one reported daily contact with children younger than 5 years and children aged 5-9 years in the two study seasons. This person was also positive at three of six sampling points during the first study season.

There were five instances in which both members of the household were carriers in the same season, although not necessarily at the same timepoint. Numbers were too small to determine whether transmission had occurred between the household pairs.

Contact with a 24- to 59-month-old child (older than 2 years but younger than 5 years) had the strongest association with elevated odds of carrying pneumococcus, the authors reported in their preprint, although the frequency and intensity of contact also mattered.

At any sampled time (point prevalence), pneumococcal carriage was substantially — just over sixfold — higher among older adults who had contact with children daily or every few days (10%) than among those who had no contact with children (1.6%).

In particular, contact between adults and children younger than 5 years and children aged 5-9 years was found to lead to elevated point prevalences of 13.8% and 14.1%, respectively. Pneumococcal carriage in children older than 10 years was lower, with a point prevalence of 8.3%.

The younger the child, the greater the point prevalence; point prevalences were 13.8% for samples from children aged 1 year and younger, 10.5% for samples from children aged 1-2 years, and 17.8% for children aged 2-5 years.

Carriage prevalence was higher in older adults who reported daily contact with children (15.7%) or contact every few days (14.0%) than in those who reported contact with children only once or twice a month (4.5%) or never (1.8%), they wrote.

“Older people who have a lot of contact with kids and are more susceptible to respiratory viruses can get a secondary infection from pneumococcus, especially during the cold and flu seasons. Vaccination can help to protect them or lessen severity of the illness,” Wyllie pointed out.

However, adult PCV immunization may not have a major impact on onward transmission to other adults, the authors wrote in their preprint.

This study supports prior work demonstrating that pneumococcal colonization is greater in households with children than in those without, said Stephen Pelton, MD, a pediatric infectious disease specialist from Boston University schools of medicine and public health. “The unique aspect is that Dr. Wyllie’s group has looked at individuals over age 60 and used the most sensitive methods currently available to detect pneumococcal carriage.”

“At the most recent ISPPD [International Society of Pneumonia and Pneumococcal Diseases conference], the role of adult-to-adult transmission in the community was discussed. This study confirms the critical role children play in community transmission of the pneumococcus,” Dr. Pelton noted.

Dr. Wyllie received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Primary Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is the principal investigator on research grants from Pfizer, Merck, NIH RADx-UP, and SalivaDirect, Inc. to Yale University and from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. Dr. Pelton received honoraria from Merck, Pfizer, Sanofi, and GSK for participation in Pneumococcal Advisory Boards and DSMB (Sanofi). Boston Medical Center received grant funding for investigator-initiated research from Merck and Pfizer.
 

A version of this article appeared on Medscape.com.

VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.

Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians. 

Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.

“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.

BMI Limitations Misses Body Composition 

If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.

“Use of BMI has its limitations, for example, it does not distinguish between body composition compartments — so between muscle and fat mass, nor does it detect changes across the lifespan of an individual [for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out. 

This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups. 

The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.

The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity. 

Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30. 

The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences. 

Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases

In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher. 

“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.” 

Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.

“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”

Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene. 

Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?

“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded. 

Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience. 

A version of this article appeared on Medscape.com.

VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.

Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians. 

Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.

“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.

BMI Limitations Misses Body Composition 

If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.

“Use of BMI has its limitations, for example, it does not distinguish between body composition compartments — so between muscle and fat mass, nor does it detect changes across the lifespan of an individual [for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out. 

This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups. 

The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.

The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity. 

Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30. 

The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences. 

Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases

In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher. 

“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.” 

Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.

“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”

Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene. 

Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?

“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded. 

Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience. 

A version of this article appeared on Medscape.com.

VENICE, ITALY — Obesity as defined by adiposity measures corresponds to a lower body mass index (BMI) cutoff (≥ 27) in men and women of middle age or older than does the widely used conventional obesity threshold of ≥ 30, shows a study performed in Italy.

Presenting at this year’s European Congress on Obesity (ECO), researchers from the University of Rome Tor Vergata and University of Modena and Reggio Emilia, Italy, and Beirut Arab University, Lebanon, conducted the study to compare the validity of the traditional World Health Organization (WHO) BMI threshold for obesity classification (≥ 30) vs adiposity levels as an alternative measure in middle-aged and older Italians. 

Marwan El Ghoch, PhD, a professor in the Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, presented the findings as a poster (GC4.152). “If you classify obesity with only BMI and without consideration of body composition, then this will not be enough. I believe BMI can be considered as a screening starting point, but we need to understand the body composition of fat and muscle too,” he said.

“We recommend this new cutoff point be applied in clinical settings when screening individuals for obesity in Italy,” El Ghoch asserted.

BMI Limitations Misses Body Composition 

If obesity is a chronic disease defined as excessive accumulation of body fat and leading to increased risk for disease, disability, and mortality, then “the identification of obesity based on body fat measurements is the most reliable method,” but he acknowledged that measuring this is not readily available in most clinical settings, and as such, “simple BMI has a place,” Dr. El Ghoch said.

“Use of BMI has its limitations, for example, it does not distinguish between body composition compartments — so between muscle and fat mass, nor does it detect changes across the lifespan of an individual [for example, the shift to more fat and less muscle with age] and it varies by ethnicity,” he pointed out. 

This led El Ghoch to ask whether using BMI as a threshold for obesity was suitable for all age groups. 

The researchers included 4800 participants of mixed gender aged 40-80 years of age. Based on the WHO’s BMI classification, 1087 people had normal body weight, 1826 had overweight, and 1887 had obesity. The participants were then categorized by adiposity status on the basis of the total body fat percentage as measured by dual-energy x-ray absorptiometry (DXA), and obesity was predicted by statistical analysis.

The analysis found that around 38% of men and 41% of women had a BMI ≥ 30 based on conventional BMI criteria, indicating obesity. However, when assessed according to body fat percentage, around 71% of the men and 64% of the women were determined to have obesity. 

Dr. El Ghoch and his colleagues calculated that a lower BMI cutoff of around 27 for obesity in people older than 40 years may be more appropriate than the existing BMI threshold of 30. 

The researchers noted some limitations of their work, including that it was a single-center, cross-sectional observational study conducted in one area of Italy. In addition, they did not account for possible confounders, such as dietary habits, and physical activity patterns, and sleep health, all of which can increase the likelihood of obesity and may interact with age-related differences. 

Missing a Significant Proportion of the Population at Risk for Obesity-Related Diseases

In an interview, Luca Busetto, MD, obesity specialist and research assistant at the Center for the Study and the Integrated Treatment of the Obesity, University of Padova, Italy, and local ECO president, commented on the study and the issue of BMI as a measure and threshold. “I think the problem we face with a classic cutoff using BMI is that we miss a significant group of people who have BMI less than 30 but have a high fat mass,” he said, adding, “but these people have the same risk of developing chronic diseases as those people with higher BMI. If they have a bad fat distribution, then their risk of complications is even higher. 

“Dr El Ghoch’s study underlines the lack of treatment for this significant part of the population,” he remarked. “We also need to use waist circumference and waist-to-height [ratio] as additional measures in this population.” 

Dr. Busetto also presented a population-based study at ECO that included over 400,000 people with a follow-up of 8 years. “We found the risk of developing obesity complications, including type 2 diabetes, hypertension, osteoarthritis, and cardiovascular disease, is not only dependent on BMI but [also] dependent on your waist-to-height ratio,” he said, highlighting that “some of these complications are only predicted by the waist-to-height ratio and not by your BMI — in particular cardiovascular diseases.

“I honestly think any screening process today needs to include both BMI and waist-to-height ratio. Having a DXA scan is great in a specialist setting, but routinely we need a measure that is valid in every office in every country and small town.”

Francesco Rubino, MD, chair of metabolic and bariatric surgery at King›s College London, United Kingdom, also remarked that understanding the changes in fat and lean mass proportions and distribution in middle years will affect health in later life, and importantly from a clinical perspective, it is a time where there is still some opportunity to intervene. 

Reflecting further on how it underscores the limitations of BMI in misclassifying people as having obesity or not, Rubino asked, “Importantly, does this make a difference to health and longevity? Really, we need an active measure of adiposity first, and then even if we do say someone has obesity — so excess adiposity — then does this translate into illness, because [excess adiposity] does not translate into disease for every individual?

“Any measure we use as a diagnostic criterion needs to reflect the ongoing disease in an individual, not only the risk of future disease — because not every person experiences this. As a doctor, we deal with the individual and how the diagnosis of disease relates to the individual in a clinic now, as well as the risk of tomorrow,” he concluded. 

Dr. El Ghoch declares no conflicts of interest. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, MetaDeq, GHP Scientific, and ViBo Health for no remuneration. Dr. Busetto discloses relationships with Burno Farmaceutici, Novo Nordisk, PronoKal, Rhythm, and Therascience. 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.