Rare Diseases

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 — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

• Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
• Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
• Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

• Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
• Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
• Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
• Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology. 

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

vutipragesahuledustukumuroceuuwefracawonauowragoslurajosadrethodrejuwraswocradawrocrapobebithagirespodrowapawrugiuochobaprustoverecewrepabribromebutiphiclislupanacrasuslishumitislojethoclepabajegibacrolo

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

chetrabibrocrinutipishoprouodawubochushetibreshororuvustuphatrodadrofrepesheneclimothosilispucewriclamabisanibisiberiwowru

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

[embed:render:related:node:238910]

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

vutipragesahuledustukumuroceuuwefracawonauowragoslurajosadrethodrejuwraswocradawrocrapobebithagirespodrowapawrugiuochobaprustoverecewrepabribromebutiphiclislupanacrasuslishumitislojethoclepabajegibacrolo

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

chetrabibrocrinutipishoprouodawubochushetibreshororuvustuphatrodadrofrepesheneclimothosilispucewriclamabisanibisiberiwowru

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

[embed:render:related:node:238910]

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no disclosures.

A version of this article appeared on Medscape.com .

Skin manifestations are common in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and present early in the disease course. Additionally, the most common histologic findings include leukocytoclastic vasculitis, neutrophilic dermatosis, and perivascular dermatitis; different variants in the UBA1 gene are associated with specific skin manifestations.

Those are key findings from a cohort study of 112 patients with VEXAS published online in JAMA Dermatology. The study, conducted by researchers at the National Institutes of Health (NIH) and several other institutions, aimed to define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histologic, and other clinical findings.

vutipragesahuledustukumuroceuuwefracawonauowragoslurajosadrethodrejuwraswocradawrocrapobebithagirespodrowapawrugiuochobaprustoverecewrepabribromebutiphiclislupanacrasuslishumitislojethoclepabajegibacrolo

First described in 2020, VEXAS syndrome is an adult-onset multisystem disease that can pose a diagnostic challenge to clinicians, the study’s corresponding author, Edward W. Cowen, MD, MHSc, of the dermatology branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), said in an interview. The disease is caused by pathogenic variants in the UBA1 gene, located on the X chromosome. Affected individuals exhibit a wide range of manifestations, including cytopenia/myelodysplasia, multiorgan systemic inflammation, and cutaneous involvement.

“Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Dr. Cowen said in an interview. “Although skin involvement occurs in more than 80% of patients, it is pleomorphic and may resemble a variety of other conditions such as vasculitis and Sweet syndrome.”

To better understand the cutaneous manifestations of VEXAS syndrome, the researchers evaluated data from 112 patients with VEXAS-defining genetic variants in the UBA1 gene between 2019 and 2023. Of the 112 patients, 73 underwent medical record review only, and 39 were prospectively evaluated at NIH. All but one of the patients were men, 94% were White individuals, and their mean age was 64 years. Skin involvement occurred in 83% of cases and was the most common presenting feature of VEXAS in 61% of cases.

Of the 64 histopathologic reports available from 60 patients, the main skin histopathologic findings were leukocytoclastic vasculitis in 23 patients (36%), neutrophilic dermatosis in 22 patients (34%), and perivascular dermatitis in 19 patients (30%). According to Dr. Cowen, one key histologic finding was a distinct pattern of “histiocytoid” dermal neutrophilic inflammation, which was present in 13 of 15 specimens (86%) that underwent central re-review. “This pattern can occasionally also be seen in patients with Sweet syndrome, unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” he said.

chetrabibrocrinutipishoprouodawubochushetibreshororuvustuphatrodadrofrepesheneclimothosilispucewriclamabisanibisiberiwowru

“Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS. This myeloid predominant pattern of skin inflammation was also most strongly associated with the leucine pathogenic variant of the UBA1 gene.” In contrast, cutaneous vasculitis was most strongly associated with the valine pathogenic variant of UBA1. “This is important because the valine variant has been previously independently linked to decreased survival,” he said.

In findings related to pathogenic genetic variants, the researchers observed that the p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates in 14 of 17 patients (82%) with this variant and often resembled histiocytoid Sweet syndrome. In addition, the p.Met41Val variant was associated with vasculitic lesions in 11 of 20 patients (55%) with this variant and with a mixed leukocytic infiltrate in 17 of these 20 patients (85%).
 

Treatment Outcomes

In the realm of therapies, skin manifestations improved in 67 of 73 patients (92%) treated with oral prednisone, while treatment with the interleukin-1 receptor antagonist anakinra improved cutaneous disease in 9 of the 16 (56%) who received it. However, 12 (75%) of those who received anakinra developed severe injection-site reactions, including ulceration in two patients and abscess formation in one patient.

Dr. Cowen noted that VEXAS is associated with high mortality (22% in this cohort), and a high degree of suspicion is required to diagnose patients with VEXAS before significant end organ damage has occurred. “This diagnosis should be considered in all older male patients who present with neutrophilic dermatosis — particularly histiocytoid Sweet syndrome, vasculitis, or leukocytoclasia without vasculitis. Patients who appear to have isolated skin involvement may have cytopenias and acute phase reactants. Therefore, complete blood count with differential and ESR and CRP should be considered to investigate for macrocytosis, cytopenias, and systemic inflammation.”

He acknowledged certain limitations of the study, including the fact that many patients were first evaluated at the NIH after having disease symptoms for many months or years. “It is possible that patients with VEXAS referred to the NIH, either for genetic testing or in person evaluation, represent a population with more aggressive disease.”

[embed:render:related:node:238910]

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the study, emphasized the importance of the UBA1 mutation in the diagnosis of this complex syndrome. “Dermatologists should be aware of VEXAS syndrome as the majority of patients present with skin lesions, which can range from urticarial to Sweet syndrome–like to palpable purpura,” Dr. Ko said.

“Chondritis and periorbital edema, sometimes unilateral, are also associated. Histopathologic clues include a predominantly histiocytoid infiltrate,” she noted. In addition, “the prominent myxoid stroma around blood vessels and adnexal structures as a clue to VEXAS syndrome surprised me; I had not read that before.”

The study was supported by the Intramural Research Program of NIAMS. One of the study authors reported personal fees from Alexion, Novartis, and Sobi outside of the submitted work. No other disclosures were reported. Dr. Ko reported having no 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.

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 — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sarilumab (Kevzara) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) for patients weighing ≥ 63 kg (139 lb). 

“Polyarticular juvenile idiopathic arthritis (JIA) can be a painful disease for children where multiple joints are impacted by this chronic inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron in a press release. 

It is estimated that nearly 300,000 children in the United States have JIA, and 1 in 4 of them have pJIA, according to the Arthritis Foundation. 

fda_icon2_web.jpg

“Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment,” Dr. Yancopoulos continued. “The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.” 

Sarilumab, jointly developed by Sanofi and Regeneron, is an interleukin 6 receptor blocker. It was first approved in 2017 for the treatment of moderate to severely active rheumatoid arthritis (RA) in adults who had inadequate response or intolerance to at least one other disease-modifying antirheumatic drug (DMARD). 

In 2023, the FDA approved sarilumab as the first biologic treatment for polymyalgia rheumatica in adults who had inadequate response to corticosteroids and could not tolerate a corticosteroid taper. 

For pJIA, sarilumab is administered subcutaneously using a 200-mg/1.14-mL prefilled syringe once every 2 weeks. The medication can be used alone or in combination with other conventional DMARDs. 

“Use of KEVZARA in pediatric patients with pJIA is supported by evidence from adequate and well-controlled studies of KEVZARA in adults with RA, pharmacokinetic data from adult patients with RA,” and pharmacokinetic comparability in 101 pediatric patients aged 2-17 years treated with sarilumab, according to the prescribing information. Sarilumab is not approved for pediatric patients < 63 kg “because of a lack of an appropriate dosage form.” 

The most common reported adverse reactions for sarilumab in pJIA are nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The pJIA trial recorded no new adverse reactions or safety concerns, compared with patients with RA. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sarilumab (Kevzara) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) for patients weighing ≥ 63 kg (139 lb). 

“Polyarticular juvenile idiopathic arthritis (JIA) can be a painful disease for children where multiple joints are impacted by this chronic inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron in a press release. 

It is estimated that nearly 300,000 children in the United States have JIA, and 1 in 4 of them have pJIA, according to the Arthritis Foundation. 

fda_icon2_web.jpg

“Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment,” Dr. Yancopoulos continued. “The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.” 

Sarilumab, jointly developed by Sanofi and Regeneron, is an interleukin 6 receptor blocker. It was first approved in 2017 for the treatment of moderate to severely active rheumatoid arthritis (RA) in adults who had inadequate response or intolerance to at least one other disease-modifying antirheumatic drug (DMARD). 

In 2023, the FDA approved sarilumab as the first biologic treatment for polymyalgia rheumatica in adults who had inadequate response to corticosteroids and could not tolerate a corticosteroid taper. 

For pJIA, sarilumab is administered subcutaneously using a 200-mg/1.14-mL prefilled syringe once every 2 weeks. The medication can be used alone or in combination with other conventional DMARDs. 

“Use of KEVZARA in pediatric patients with pJIA is supported by evidence from adequate and well-controlled studies of KEVZARA in adults with RA, pharmacokinetic data from adult patients with RA,” and pharmacokinetic comparability in 101 pediatric patients aged 2-17 years treated with sarilumab, according to the prescribing information. Sarilumab is not approved for pediatric patients < 63 kg “because of a lack of an appropriate dosage form.” 

The most common reported adverse reactions for sarilumab in pJIA are nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The pJIA trial recorded no new adverse reactions or safety concerns, compared with patients with RA. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sarilumab (Kevzara) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) for patients weighing ≥ 63 kg (139 lb). 

“Polyarticular juvenile idiopathic arthritis (JIA) can be a painful disease for children where multiple joints are impacted by this chronic inflammation,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron in a press release. 

It is estimated that nearly 300,000 children in the United States have JIA, and 1 in 4 of them have pJIA, according to the Arthritis Foundation. 

fda_icon2_web.jpg

“Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment,” Dr. Yancopoulos continued. “The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.” 

Sarilumab, jointly developed by Sanofi and Regeneron, is an interleukin 6 receptor blocker. It was first approved in 2017 for the treatment of moderate to severely active rheumatoid arthritis (RA) in adults who had inadequate response or intolerance to at least one other disease-modifying antirheumatic drug (DMARD). 

In 2023, the FDA approved sarilumab as the first biologic treatment for polymyalgia rheumatica in adults who had inadequate response to corticosteroids and could not tolerate a corticosteroid taper. 

For pJIA, sarilumab is administered subcutaneously using a 200-mg/1.14-mL prefilled syringe once every 2 weeks. The medication can be used alone or in combination with other conventional DMARDs. 

“Use of KEVZARA in pediatric patients with pJIA is supported by evidence from adequate and well-controlled studies of KEVZARA in adults with RA, pharmacokinetic data from adult patients with RA,” and pharmacokinetic comparability in 101 pediatric patients aged 2-17 years treated with sarilumab, according to the prescribing information. Sarilumab is not approved for pediatric patients < 63 kg “because of a lack of an appropriate dosage form.” 

The most common reported adverse reactions for sarilumab in pJIA are nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The pJIA trial recorded no new adverse reactions or safety concerns, compared with patients with RA. 
 

A version of this article appeared on Medscape.com.

The records came in by fax. A patient who’d recently moved here and needed to connect with a local neurologist.

When I had time, I flipped through the records. He needed ongoing treatment for a rare neurological disease that I’d heard of, but wasn’t otherwise familiar with. It didn’t even exist in the textbooks or conferences when I was in residency. I’d never seen a case of it, just read about it here and there in journals.

Block_Allan_M_AZ_web.JPG

I looked it up, reviewed current treatment options, monitoring, and other knowledge about it, then stared at the notes for a minute. Finally, after thinking it over, I attached a sticky note for my secretary that, if the person called, to redirect them to one of the local subspecialty neurology centers.

I have nothing against this patient, but realistically he would be better served seeing someone with time to keep up on advancements in esoteric disorders, not a general neurologist like myself.

Isn’t that why we have subspecialty centers?

Some of it is also me. There was a time in my career when keeping up on newly discovered disorders and their treatments was, well, cool. But after 25 years in practice, that changes.

In the daily trenches of general neurology, one can only be on top of so much. You have to prioritize the things you’re most likely to see. It’s important to be at least somewhat aware of new developments (such as in this case) as you may encounter them, and need to know when it’s something you can handle and when to send it elsewhere.

Driving home that afternoon I thought, “I’m an old dog. I don’t want to learn new tricks.” Maybe that’s all it is. There are other neurologists my age and older who thrive on the challenge of learning about and treating new and rare disorders that were unknown when they started out. There’s nothing wrong with that.

But I’ve never pretended to be an academic or sub-sub-specialist. My patients depend on me to stay up to date on the large number of commonly seen neurological disorders, and I do my best to do that.

It ain’t easy being an old dog.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

The records came in by fax. A patient who’d recently moved here and needed to connect with a local neurologist.

When I had time, I flipped through the records. He needed ongoing treatment for a rare neurological disease that I’d heard of, but wasn’t otherwise familiar with. It didn’t even exist in the textbooks or conferences when I was in residency. I’d never seen a case of it, just read about it here and there in journals.

Block_Allan_M_AZ_web.JPG

I looked it up, reviewed current treatment options, monitoring, and other knowledge about it, then stared at the notes for a minute. Finally, after thinking it over, I attached a sticky note for my secretary that, if the person called, to redirect them to one of the local subspecialty neurology centers.

I have nothing against this patient, but realistically he would be better served seeing someone with time to keep up on advancements in esoteric disorders, not a general neurologist like myself.

Isn’t that why we have subspecialty centers?

Some of it is also me. There was a time in my career when keeping up on newly discovered disorders and their treatments was, well, cool. But after 25 years in practice, that changes.

In the daily trenches of general neurology, one can only be on top of so much. You have to prioritize the things you’re most likely to see. It’s important to be at least somewhat aware of new developments (such as in this case) as you may encounter them, and need to know when it’s something you can handle and when to send it elsewhere.

Driving home that afternoon I thought, “I’m an old dog. I don’t want to learn new tricks.” Maybe that’s all it is. There are other neurologists my age and older who thrive on the challenge of learning about and treating new and rare disorders that were unknown when they started out. There’s nothing wrong with that.

But I’ve never pretended to be an academic or sub-sub-specialist. My patients depend on me to stay up to date on the large number of commonly seen neurological disorders, and I do my best to do that.

It ain’t easy being an old dog.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

The records came in by fax. A patient who’d recently moved here and needed to connect with a local neurologist.

When I had time, I flipped through the records. He needed ongoing treatment for a rare neurological disease that I’d heard of, but wasn’t otherwise familiar with. It didn’t even exist in the textbooks or conferences when I was in residency. I’d never seen a case of it, just read about it here and there in journals.

Block_Allan_M_AZ_web.JPG

I looked it up, reviewed current treatment options, monitoring, and other knowledge about it, then stared at the notes for a minute. Finally, after thinking it over, I attached a sticky note for my secretary that, if the person called, to redirect them to one of the local subspecialty neurology centers.

I have nothing against this patient, but realistically he would be better served seeing someone with time to keep up on advancements in esoteric disorders, not a general neurologist like myself.

Isn’t that why we have subspecialty centers?

Some of it is also me. There was a time in my career when keeping up on newly discovered disorders and their treatments was, well, cool. But after 25 years in practice, that changes.

In the daily trenches of general neurology, one can only be on top of so much. You have to prioritize the things you’re most likely to see. It’s important to be at least somewhat aware of new developments (such as in this case) as you may encounter them, and need to know when it’s something you can handle and when to send it elsewhere.

Driving home that afternoon I thought, “I’m an old dog. I don’t want to learn new tricks.” Maybe that’s all it is. There are other neurologists my age and older who thrive on the challenge of learning about and treating new and rare disorders that were unknown when they started out. There’s nothing wrong with that.

But I’ve never pretended to be an academic or sub-sub-specialist. My patients depend on me to stay up to date on the large number of commonly seen neurological disorders, and I do my best to do that.

It ain’t easy being an old dog.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Upadacitinib (Rinvoq) is now indicated for patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis (pJIA) and psoriatic arthritis (PsA) who cannot tolerate or achieve adequate disease response with one or more tumor necrosis factor (TNF) blockers, according to a press release from manufacturer AbbVie. 

For the youngest patients, upadacitinib is also available as a weight-based oral solution (Rinvoq LQ) in addition to the previously available tablets, according to the company. JIA, which includes pJIA and juvenile PsA, affects nearly 300,000 children and adolescents in the United States, and alternatives to TNF inhibitor (TNFi) therapy are limited, according to the company. 

FDA_icon3_web.jpg

“Pediatric patients with pJIA and PsA can be severely limited in their ability to complete daily physical tasks and participate in everyday activities. Understanding their needs today and knowing the likelihood of disease in adulthood underscores the need for additional treatment options,” Aarat Patel, MD, a pediatric rheumatologist at Bon Secours Rheumatology Center, Richmond, Virginia, said in the press release. “Having a treatment option available for patients who do not respond well to a TNFi addresses a need for the healthcare community, patients, and their families,” he said.

Upadacitinib, a Janus kinase (JAK) inhibitor, is being studied for multiple immune-mediated inflammatory diseases. The new indication was supported by data from adults with rheumatoid arthritis (RA) and PsA, 51 pediatric patients with pJIA and active polyarthritis, and safety data from 83 pediatric patients aged 2 years to younger than 18 years with pJIA and active polyarthritis. 

In the studies, the drug’s safety in pediatric patients was similar to the known safety profile in adults, which includes increased risk for serious infections such as tuberculosis, cancer, immune system problems, blood clots, and serious allergic reactions to components of the drug, according to the press release. However, the safety and effectiveness of upadacitinib for pJIA and PsA in patients younger than 2 years are unknown.

“Upadacitinib plasma exposures in pediatric patients with pJIA and PsA at the recommended dosage are predicted to be comparable to those observed in adults with RA and PsA based on population pharmacokinetic modeling and simulation,” according to the press release.

Currently, upadacitinib’s only other pediatric indication is for moderate to severe atopic dermatitis in children aged 12 years or older. Upadacitinib also is indicated for treatment of adults with moderate to severe RA, active PsA, active ankylosing spondylitis, active nonradiographic axial spondyloarthritis, and moderate to severe ulcerative colitis and Crohn’s disease, but safety and efficacy for its use in treatment of these conditions in children and adolescents is unknown.

Upadacitinib also is being studied in phase 3 trials for treatment of conditions including alopecia areata, ankylosing spondylitis, atopic dermatitis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, hidradenitis suppurativa, psoriatic arthritis, RA, systemic lupus erythematosus, Takayasu arteritis, ulcerative colitis, and vitiligo, according to the press release. 

Full prescribing information and safety data for upadacitinib are available here. 

A version of this article appeared on Medscape.com.

Upadacitinib (Rinvoq) is now indicated for patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis (pJIA) and psoriatic arthritis (PsA) who cannot tolerate or achieve adequate disease response with one or more tumor necrosis factor (TNF) blockers, according to a press release from manufacturer AbbVie. 

For the youngest patients, upadacitinib is also available as a weight-based oral solution (Rinvoq LQ) in addition to the previously available tablets, according to the company. JIA, which includes pJIA and juvenile PsA, affects nearly 300,000 children and adolescents in the United States, and alternatives to TNF inhibitor (TNFi) therapy are limited, according to the company. 

FDA_icon3_web.jpg

“Pediatric patients with pJIA and PsA can be severely limited in their ability to complete daily physical tasks and participate in everyday activities. Understanding their needs today and knowing the likelihood of disease in adulthood underscores the need for additional treatment options,” Aarat Patel, MD, a pediatric rheumatologist at Bon Secours Rheumatology Center, Richmond, Virginia, said in the press release. “Having a treatment option available for patients who do not respond well to a TNFi addresses a need for the healthcare community, patients, and their families,” he said.

Upadacitinib, a Janus kinase (JAK) inhibitor, is being studied for multiple immune-mediated inflammatory diseases. The new indication was supported by data from adults with rheumatoid arthritis (RA) and PsA, 51 pediatric patients with pJIA and active polyarthritis, and safety data from 83 pediatric patients aged 2 years to younger than 18 years with pJIA and active polyarthritis. 

In the studies, the drug’s safety in pediatric patients was similar to the known safety profile in adults, which includes increased risk for serious infections such as tuberculosis, cancer, immune system problems, blood clots, and serious allergic reactions to components of the drug, according to the press release. However, the safety and effectiveness of upadacitinib for pJIA and PsA in patients younger than 2 years are unknown.

“Upadacitinib plasma exposures in pediatric patients with pJIA and PsA at the recommended dosage are predicted to be comparable to those observed in adults with RA and PsA based on population pharmacokinetic modeling and simulation,” according to the press release.

Currently, upadacitinib’s only other pediatric indication is for moderate to severe atopic dermatitis in children aged 12 years or older. Upadacitinib also is indicated for treatment of adults with moderate to severe RA, active PsA, active ankylosing spondylitis, active nonradiographic axial spondyloarthritis, and moderate to severe ulcerative colitis and Crohn’s disease, but safety and efficacy for its use in treatment of these conditions in children and adolescents is unknown.

Upadacitinib also is being studied in phase 3 trials for treatment of conditions including alopecia areata, ankylosing spondylitis, atopic dermatitis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, hidradenitis suppurativa, psoriatic arthritis, RA, systemic lupus erythematosus, Takayasu arteritis, ulcerative colitis, and vitiligo, according to the press release. 

Full prescribing information and safety data for upadacitinib are available here. 

A version of this article appeared on Medscape.com.

Upadacitinib (Rinvoq) is now indicated for patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis (pJIA) and psoriatic arthritis (PsA) who cannot tolerate or achieve adequate disease response with one or more tumor necrosis factor (TNF) blockers, according to a press release from manufacturer AbbVie. 

For the youngest patients, upadacitinib is also available as a weight-based oral solution (Rinvoq LQ) in addition to the previously available tablets, according to the company. JIA, which includes pJIA and juvenile PsA, affects nearly 300,000 children and adolescents in the United States, and alternatives to TNF inhibitor (TNFi) therapy are limited, according to the company. 

FDA_icon3_web.jpg

“Pediatric patients with pJIA and PsA can be severely limited in their ability to complete daily physical tasks and participate in everyday activities. Understanding their needs today and knowing the likelihood of disease in adulthood underscores the need for additional treatment options,” Aarat Patel, MD, a pediatric rheumatologist at Bon Secours Rheumatology Center, Richmond, Virginia, said in the press release. “Having a treatment option available for patients who do not respond well to a TNFi addresses a need for the healthcare community, patients, and their families,” he said.

Upadacitinib, a Janus kinase (JAK) inhibitor, is being studied for multiple immune-mediated inflammatory diseases. The new indication was supported by data from adults with rheumatoid arthritis (RA) and PsA, 51 pediatric patients with pJIA and active polyarthritis, and safety data from 83 pediatric patients aged 2 years to younger than 18 years with pJIA and active polyarthritis. 

In the studies, the drug’s safety in pediatric patients was similar to the known safety profile in adults, which includes increased risk for serious infections such as tuberculosis, cancer, immune system problems, blood clots, and serious allergic reactions to components of the drug, according to the press release. However, the safety and effectiveness of upadacitinib for pJIA and PsA in patients younger than 2 years are unknown.

“Upadacitinib plasma exposures in pediatric patients with pJIA and PsA at the recommended dosage are predicted to be comparable to those observed in adults with RA and PsA based on population pharmacokinetic modeling and simulation,” according to the press release.

Currently, upadacitinib’s only other pediatric indication is for moderate to severe atopic dermatitis in children aged 12 years or older. Upadacitinib also is indicated for treatment of adults with moderate to severe RA, active PsA, active ankylosing spondylitis, active nonradiographic axial spondyloarthritis, and moderate to severe ulcerative colitis and Crohn’s disease, but safety and efficacy for its use in treatment of these conditions in children and adolescents is unknown.

Upadacitinib also is being studied in phase 3 trials for treatment of conditions including alopecia areata, ankylosing spondylitis, atopic dermatitis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis, hidradenitis suppurativa, psoriatic arthritis, RA, systemic lupus erythematosus, Takayasu arteritis, ulcerative colitis, and vitiligo, according to the press release. 

Full prescribing information and safety data for upadacitinib are available here. 

A version of this article appeared on Medscape.com.

TOPLINE:

Inebilizumab-cdon, a monoclonal antibody that depletes B cells, reduces the risk for flares without showing any new safety signals in patients with immunoglobulin G4-related disease (IgG4-RD) who have multiorgan disease and are on glucocorticoid therapy.

METHODOLOGY:

• IgG4-RD is an immune-mediated, fibroinflammatory condition that affects multiple organs, causing irreversible organ damage. MITIGATE is the first multinational, placebo-controlled trial involving patients with IgG4-RD.
• Researchers evaluated the efficacy and safety of inebilizumab in 135 adult patients at risk for flares due to a history of multiorgan disease and active disease requiring treatment with glucocorticoids.
• The patients were randomly assigned to receive 300-mg intravenous inebilizumab or placebo on day 1, day 15, and week 26.
• The primary endpoint was the time to the first treated and adjudicated IgG4-RD flare within 52 weeks.
• The secondary endpoints included the annualized flare rate, flare-free and treatment-free complete remission, and flare-free and corticosteroid-free complete remission.

TAKEAWAY:

• Compared with the placebo, inebilizumab reduced the risk for IgG4-RD flares by 87% during the 52-week trial period (hazard ratio, 0.13; P < .0001).
• All the secondary endpoints showed improvement following treatment with inebilizumab.
• The most common adverse reactions with inebilizumab, as observed in a previous trial for neuromyelitis optica spectrum disorder, were urinary tract infection and arthralgia.
• There were no new safety signals in the MITIGATE trial.

IN PRACTICE:

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD but also key insights into the nature of this condition,” John Stone, MD, MPH, principal investigator, said in a news release.

SOURCE:

Dr. Stone, a professor of medicine at the Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, Boston, led this study.

LIMITATIONS:

This press release did not discuss any limitations of the current study.

DISCLOSURES:

This study was funded by Mitsubishi Tanabe Pharma and Hansoh Pharma and sponsored by Amgen. The author disclosures were not available.

A version of this article appeared on Medscape.com.

TOPLINE:

Inebilizumab-cdon, a monoclonal antibody that depletes B cells, reduces the risk for flares without showing any new safety signals in patients with immunoglobulin G4-related disease (IgG4-RD) who have multiorgan disease and are on glucocorticoid therapy.

METHODOLOGY:

• IgG4-RD is an immune-mediated, fibroinflammatory condition that affects multiple organs, causing irreversible organ damage. MITIGATE is the first multinational, placebo-controlled trial involving patients with IgG4-RD.
• Researchers evaluated the efficacy and safety of inebilizumab in 135 adult patients at risk for flares due to a history of multiorgan disease and active disease requiring treatment with glucocorticoids.
• The patients were randomly assigned to receive 300-mg intravenous inebilizumab or placebo on day 1, day 15, and week 26.
• The primary endpoint was the time to the first treated and adjudicated IgG4-RD flare within 52 weeks.
• The secondary endpoints included the annualized flare rate, flare-free and treatment-free complete remission, and flare-free and corticosteroid-free complete remission.

TAKEAWAY:

• Compared with the placebo, inebilizumab reduced the risk for IgG4-RD flares by 87% during the 52-week trial period (hazard ratio, 0.13; P < .0001).
• All the secondary endpoints showed improvement following treatment with inebilizumab.
• The most common adverse reactions with inebilizumab, as observed in a previous trial for neuromyelitis optica spectrum disorder, were urinary tract infection and arthralgia.
• There were no new safety signals in the MITIGATE trial.

IN PRACTICE:

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD but also key insights into the nature of this condition,” John Stone, MD, MPH, principal investigator, said in a news release.

SOURCE:

Dr. Stone, a professor of medicine at the Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, Boston, led this study.

LIMITATIONS:

This press release did not discuss any limitations of the current study.

DISCLOSURES:

This study was funded by Mitsubishi Tanabe Pharma and Hansoh Pharma and sponsored by Amgen. The author disclosures were not available.

A version of this article appeared on Medscape.com.

TOPLINE:

Inebilizumab-cdon, a monoclonal antibody that depletes B cells, reduces the risk for flares without showing any new safety signals in patients with immunoglobulin G4-related disease (IgG4-RD) who have multiorgan disease and are on glucocorticoid therapy.

METHODOLOGY:

• IgG4-RD is an immune-mediated, fibroinflammatory condition that affects multiple organs, causing irreversible organ damage. MITIGATE is the first multinational, placebo-controlled trial involving patients with IgG4-RD.
• Researchers evaluated the efficacy and safety of inebilizumab in 135 adult patients at risk for flares due to a history of multiorgan disease and active disease requiring treatment with glucocorticoids.
• The patients were randomly assigned to receive 300-mg intravenous inebilizumab or placebo on day 1, day 15, and week 26.
• The primary endpoint was the time to the first treated and adjudicated IgG4-RD flare within 52 weeks.
• The secondary endpoints included the annualized flare rate, flare-free and treatment-free complete remission, and flare-free and corticosteroid-free complete remission.

TAKEAWAY:

• Compared with the placebo, inebilizumab reduced the risk for IgG4-RD flares by 87% during the 52-week trial period (hazard ratio, 0.13; P < .0001).
• All the secondary endpoints showed improvement following treatment with inebilizumab.
• The most common adverse reactions with inebilizumab, as observed in a previous trial for neuromyelitis optica spectrum disorder, were urinary tract infection and arthralgia.
• There were no new safety signals in the MITIGATE trial.

IN PRACTICE:

“These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD but also key insights into the nature of this condition,” John Stone, MD, MPH, principal investigator, said in a news release.

SOURCE:

Dr. Stone, a professor of medicine at the Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, Boston, led this study.

LIMITATIONS:

This press release did not discuss any limitations of the current study.

DISCLOSURES:

This study was funded by Mitsubishi Tanabe Pharma and Hansoh Pharma and sponsored by Amgen. The author disclosures were not available.

A version of this article appeared on Medscape.com.