Ted Bosworth

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.

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

trishudrebagici

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

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

trishudrebagici

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

VIENNA — To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m² (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

trishudrebagici

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

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OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

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New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

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At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

vofrojowrufrucotrijapisluprifristotephosibahuprehagibrastenodistophabedraginotirulijoswuphenebroslacisliseuauuuupravaspiduvedul

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

Conaghan _Philip_G_UK_web.jpg

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

hucaspositredaluuasl

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

vofrojowrufrucotrijapisluprifristotephosibahuprehagibrastenodistophabedraginotirulijoswuphenebroslacisliseuauuuupravaspiduvedul

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

Conaghan _Philip_G_UK_web.jpg

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

hucaspositredaluuasl

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

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

VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

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

VIENNA — Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

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

NASHVILLE, TENNESSEE — For the first time, the majority of patients with multiple sclerosis (MS) in the United States are, or soon will be, over age 55, a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.

Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said she now believes that “patient age is actually more important.”

Graves_Jennifer_Calif_web.jpg

Speaking at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC), Dr. Graves noted that it is well known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.

However, she maintains that, independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that, relative to chronological age, biologic age is more robustly correlated with MS outcomes.

In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Dr. Graves and others have shown that biologic versus chronological aging is more rapid in patients with MS than those without the disease. In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger versus older biologic age.

“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Dr. Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.

There are already many avenues of research regarding aging processes and their interaction with MS. Dr. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.
 

Shifting Priorities

The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the department of physical therapy, University of Alabama at Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.

“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Dr. Motl, another participant in the CMSC aging symposium. Dr. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.

Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.

“We need to move away from immunomodulatory agents [in older patients],” Dr. Zhang said. Older patients are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.
 

Multidisciplinary Approach

Dr. Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.

Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.

Dr. Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.

“The need is already strong and growing,” said Dr. Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.

As the clinic evolves and matures, Dr. Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.

Dr. Graves reported financial relationships with Horizon Therapeutics. Dr. Zhang reported no potential conflicts of interest. Dr. Motl reported financial relationships with Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — For the first time, the majority of patients with multiple sclerosis (MS) in the United States are, or soon will be, over age 55, a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.

Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said she now believes that “patient age is actually more important.”

Graves_Jennifer_Calif_web.jpg

Speaking at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC), Dr. Graves noted that it is well known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.

However, she maintains that, independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that, relative to chronological age, biologic age is more robustly correlated with MS outcomes.

In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Dr. Graves and others have shown that biologic versus chronological aging is more rapid in patients with MS than those without the disease. In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger versus older biologic age.

“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Dr. Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.

There are already many avenues of research regarding aging processes and their interaction with MS. Dr. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.
 

Shifting Priorities

The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the department of physical therapy, University of Alabama at Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.

“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Dr. Motl, another participant in the CMSC aging symposium. Dr. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.

Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.

“We need to move away from immunomodulatory agents [in older patients],” Dr. Zhang said. Older patients are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.
 

Multidisciplinary Approach

Dr. Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.

Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.

Dr. Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.

“The need is already strong and growing,” said Dr. Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.

As the clinic evolves and matures, Dr. Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.

Dr. Graves reported financial relationships with Horizon Therapeutics. Dr. Zhang reported no potential conflicts of interest. Dr. Motl reported financial relationships with Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — For the first time, the majority of patients with multiple sclerosis (MS) in the United States are, or soon will be, over age 55, a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.

Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said she now believes that “patient age is actually more important.”

Graves_Jennifer_Calif_web.jpg

Speaking at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC), Dr. Graves noted that it is well known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.

However, she maintains that, independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that, relative to chronological age, biologic age is more robustly correlated with MS outcomes.

In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Dr. Graves and others have shown that biologic versus chronological aging is more rapid in patients with MS than those without the disease. In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger versus older biologic age.

“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Dr. Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.

There are already many avenues of research regarding aging processes and their interaction with MS. Dr. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.
 

Shifting Priorities

The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the department of physical therapy, University of Alabama at Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.

“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Dr. Motl, another participant in the CMSC aging symposium. Dr. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.

Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.

“We need to move away from immunomodulatory agents [in older patients],” Dr. Zhang said. Older patients are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.
 

Multidisciplinary Approach

Dr. Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.

Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.

Dr. Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.

“The need is already strong and growing,” said Dr. Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.

As the clinic evolves and matures, Dr. Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.

Dr. Graves reported financial relationships with Horizon Therapeutics. Dr. Zhang reported no potential conflicts of interest. Dr. Motl reported financial relationships with Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

bruchakoraspostevusufrogophogifracronobilaprelucerishachopiniclulecidreprerotruspapruspapihulesetresputrebriuibu

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

For those involved in the treatment of gout, this outcome was inevitable, according to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina.

“We did not need a controlled trial to know that we should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes,” Dr. Klionsky said. However, she conceded that objective data might have some value for nonspecialists.

“Primary care physicians often do not recognize the importance of controlling serum uric acid or the goals of treatment,” she told this news organization. For those who know this field, T2T does not need validation. She did not doubt that the ACP will change its position on T2T when its guidelines are updated.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. In a study she presented at this year’s EULAR, rheumatologists, nephrologists, and primary care physicians were surveyed about gout remission, which is an important clinical target even if there is no standard definition.

There was general agreement among the 151 rheumatologists, 150 nephrologists, and 102 primary care physicians that the absence of flares was among the top three criteria, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as one of the top three criteria.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

bruchakoraspostevusufrogophogifracronobilaprelucerishachopiniclulecidreprerotruspapruspapihulesetresputrebriuibu

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

For those involved in the treatment of gout, this outcome was inevitable, according to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina.

“We did not need a controlled trial to know that we should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes,” Dr. Klionsky said. However, she conceded that objective data might have some value for nonspecialists.

“Primary care physicians often do not recognize the importance of controlling serum uric acid or the goals of treatment,” she told this news organization. For those who know this field, T2T does not need validation. She did not doubt that the ACP will change its position on T2T when its guidelines are updated.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. In a study she presented at this year’s EULAR, rheumatologists, nephrologists, and primary care physicians were surveyed about gout remission, which is an important clinical target even if there is no standard definition.

There was general agreement among the 151 rheumatologists, 150 nephrologists, and 102 primary care physicians that the absence of flares was among the top three criteria, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as one of the top three criteria.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.

The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.

T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 

bruchakoraspostevusufrogophogifracronobilaprelucerishachopiniclulecidreprerotruspapruspapihulesetresputrebriuibu

Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.

The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.

To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment. 

The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.

For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.

The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.

At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.

At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
 

Nonspecialists Should Heed the Results

For those involved in the treatment of gout, this outcome was inevitable, according to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina.

“We did not need a controlled trial to know that we should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes,” Dr. Klionsky said. However, she conceded that objective data might have some value for nonspecialists.

“Primary care physicians often do not recognize the importance of controlling serum uric acid or the goals of treatment,” she told this news organization. For those who know this field, T2T does not need validation. She did not doubt that the ACP will change its position on T2T when its guidelines are updated.

However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. In a study she presented at this year’s EULAR, rheumatologists, nephrologists, and primary care physicians were surveyed about gout remission, which is an important clinical target even if there is no standard definition.

There was general agreement among the 151 rheumatologists, 150 nephrologists, and 102 primary care physicians that the absence of flares was among the top three criteria, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as one of the top three criteria.

Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.

In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.

Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.

A version of this article appeared on Medscape.com.

VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.

“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.

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This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.

The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.

“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.

van_Gaalen_Floris_A_NL_web.jpg

Relative Risk for Infection on JAKi Is Unclear

Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.

The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.

Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.

For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
 

More Than 50,000 Exposures Included in Analysis

From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).

A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).

Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.

When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
 

Herpes Zoster Risk on JAKi Is > Twofold Higher

Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).

In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.

Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.

Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.

Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.

A version of this article appeared on Medscape.com.

VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.

“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.

nopeswepeseswajijochadrokeruslaswagavethispabilutugijutedrehoclowrathaslistofribrasestuprofrushuga

This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.

The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.

“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.

van_Gaalen_Floris_A_NL_web.jpg

Relative Risk for Infection on JAKi Is Unclear

Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.

The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.

Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.

For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
 

More Than 50,000 Exposures Included in Analysis

From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).

A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).

Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.

When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
 

Herpes Zoster Risk on JAKi Is > Twofold Higher

Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).

In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.

Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.

Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.

Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.

A version of this article appeared on Medscape.com.

VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.

“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.

nopeswepeseswajijochadrokeruslaswagavethispabilutugijutedrehoclowrathaslistofribrasestuprofrushuga

This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.

The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.

“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.

van_Gaalen_Floris_A_NL_web.jpg

Relative Risk for Infection on JAKi Is Unclear

Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.

The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.

Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.

For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
 

More Than 50,000 Exposures Included in Analysis

From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).

A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).

Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.

When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
 

Herpes Zoster Risk on JAKi Is > Twofold Higher

Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).

In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.

Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.

Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.

Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — A second-generation anti-CD40L monoclonal antibody suppresses multiple sclerosis (MS) disease activity on MRI to an uncommonly high degree, new trial data suggested.

Researchers found a near absence of new brain lesions at 48 weeks in patients on the highest dose. At this level of disease suppression, there was no evidence of increased infection risk, which investigators said might relate to its mechanism of action. In addition, there were no thrombotic events, which is what defeated a first-generation drug in this same class.

Among those initially randomly assigned to receive 1200 mg every 4 weeks, 96% were free of new gadolinium-positive (Gd+ T1) lesions at 48 weeks, reported investigator Yang Mao-Draayer, MD, PhD, director of Clinical and Experimental Therapeutics at the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City. Annual relapse rates were also low.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
 

No Effect on Lymphocyte Count

As previously reported, 12-week frexalimab results were noteworthy because they provided validation for CD40L as a target in the control of MS. One of the unique features of this therapy relative to many other immunomodulatory therapies is that it has shown little, if any, effect on lymphocyte counts or immunoglobulin levels.

In the double-blind randomized phase 2 trial, 125 patients with MS of all other MS therapy were randomized in a 4:4:4:1 ratio to 1200-mg frexalimab administered intravenously every 4 weeks after a loading dose, to 300-mg frexalimab administered subcutaneously every 2 weeks after a loading dose, or to one of the two matching placebo arms.

For the primary endpoint of new Gd+ T1 lesions at the end of the blinded study, the rates at week 12 were 0.2 and 0.3 in the higher- and lower-dose treatment groups, respectively, and 1.4 in the pooled placebo groups.

At 48 weeks, the results were even better. From 12 weeks, the rate of Gd+ T1 lesions in the high-dose group continued to fall, reaching 0.1 at week 24 and 0.0 at week 48. In the lower-dose group, there was also a stepwise decline over time with a value of 0.2 at week 48. The annual relapse rate at week 48 was 0.4.
 

Reengineered Agent

In the placebo groups, the same type of suppression of disease activity was observed after they were switched to active therapy at the end of 12 weeks.

By 24 weeks, the number of new Gd+ T1 lesions had fallen to 0.3 in placebo patients switched to the higher dose and 1.0 in those switched to the lower dose.

By week 48, the rates were 0.2 in both of the switch arms.

The proportions of patients free of new Gd+ T1 lesions at 48 weeks were 96% in the group started and maintained on the highest dose of frexalimab, 87% in those started and maintained on the lower dose, 90% in those started on placebo and switched to the highest dose of frexalimab, and 92% of placebo patients switched to the lower dose.

“T2 lesion volume from baseline through week 48 was stable in patients who continued receiving frexalimab and decreased in placebo participants after switching to frexalimab at week 12,” Dr. Mao-Draayer reported.

The CD40-CD40L co-stimulatory pathway that regulates both adaptive and innate immune responses has been pursued as a target for MS therapies for decades, Dr. Mao-Draayer said.

A first-generation monoclonal antibody directed at elevated levels of CD40L, which is implicated in the inflammation that drives MS, showed promise but was abandoned after it was associated with an increased risk for thromboembolic events in a phase 1 trial, she said.

However, the second-generation agent was engineered to avoid an interaction with platelets, which played a role in the risk for thrombosis associated with the failure of the earlier drug.

As with the first-generation agent, frexalimab had little or no impact on lymphocyte count or immunoglobulin G and immunoglobulin M levels. Both remained stable during the 12-week controlled trial and through the ongoing open-label extension, Dr. Mao-Draayer said.

This might be a factor in the low level of adverse events. Most importantly, there have been no thromboembolic events associated with frexalimab so far, but the follow-up data also show rates of infection and other events, such as nasopharyngitis, that were comparable with placebo in the 12-week controlled trial and have not increased over longer-term monitoring.

Such adverse events as headache and COVID-19 infection have also occurred at rates similar to placebo.

Two phase 3 trials are underway. FREXALT is being conducted in relapsing-remitting MS. FREVIV has enrolled patients with nonrelapsing secondary progressive MS.
 

Impressively Low New Lesion Count

Commenting on the findings, Jeffrey Cohen, MD, director of the Mellen Center for Multiple Sclerosis, Cleveland Clinic, who was not involved in the research, said that over the course of the extended follow-up, MS activity in the central nervous system as measured with new Gd+ T1 lesions was impressively low. 

He noted that the phase 2 open-label follow-up continues to support the promise of frexalimab. But Dr. Cohen cautioned that this does not obviate the need for phase 3 data.

In particular, he said that an immunomodulatory agent that does not affect the lymphocyte count has a theoretical advantage, but pointed out that the benefit is still presumably mediated by blocking pathways that mediate autoimmune activity.

Even if lymphocyte count is unaffected, the immunomodulatory pathway by which frexalimab does exert its benefit might pose a different set of risks, he said.

“We will not have sufficient data to judge the promise of this agent until the phase 3 trials are completed,” he said.

Dr. Mao-Draayer reported financial relationships with Acorda, Bayer, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Horizon, Janssen, Novartis, Questor, Teva, and Sanofi, which provided funding for the phase 2 frexalimab trial. Dr. Cohen reported financial relationships with Astoria, Convelo, EMD Serono, FiND, INmune, and Sandoz.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — A second-generation anti-CD40L monoclonal antibody suppresses multiple sclerosis (MS) disease activity on MRI to an uncommonly high degree, new trial data suggested.

Researchers found a near absence of new brain lesions at 48 weeks in patients on the highest dose. At this level of disease suppression, there was no evidence of increased infection risk, which investigators said might relate to its mechanism of action. In addition, there were no thrombotic events, which is what defeated a first-generation drug in this same class.

Among those initially randomly assigned to receive 1200 mg every 4 weeks, 96% were free of new gadolinium-positive (Gd+ T1) lesions at 48 weeks, reported investigator Yang Mao-Draayer, MD, PhD, director of Clinical and Experimental Therapeutics at the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City. Annual relapse rates were also low.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
 

No Effect on Lymphocyte Count

As previously reported, 12-week frexalimab results were noteworthy because they provided validation for CD40L as a target in the control of MS. One of the unique features of this therapy relative to many other immunomodulatory therapies is that it has shown little, if any, effect on lymphocyte counts or immunoglobulin levels.

In the double-blind randomized phase 2 trial, 125 patients with MS of all other MS therapy were randomized in a 4:4:4:1 ratio to 1200-mg frexalimab administered intravenously every 4 weeks after a loading dose, to 300-mg frexalimab administered subcutaneously every 2 weeks after a loading dose, or to one of the two matching placebo arms.

For the primary endpoint of new Gd+ T1 lesions at the end of the blinded study, the rates at week 12 were 0.2 and 0.3 in the higher- and lower-dose treatment groups, respectively, and 1.4 in the pooled placebo groups.

At 48 weeks, the results were even better. From 12 weeks, the rate of Gd+ T1 lesions in the high-dose group continued to fall, reaching 0.1 at week 24 and 0.0 at week 48. In the lower-dose group, there was also a stepwise decline over time with a value of 0.2 at week 48. The annual relapse rate at week 48 was 0.4.
 

Reengineered Agent

In the placebo groups, the same type of suppression of disease activity was observed after they were switched to active therapy at the end of 12 weeks.

By 24 weeks, the number of new Gd+ T1 lesions had fallen to 0.3 in placebo patients switched to the higher dose and 1.0 in those switched to the lower dose.

By week 48, the rates were 0.2 in both of the switch arms.

The proportions of patients free of new Gd+ T1 lesions at 48 weeks were 96% in the group started and maintained on the highest dose of frexalimab, 87% in those started and maintained on the lower dose, 90% in those started on placebo and switched to the highest dose of frexalimab, and 92% of placebo patients switched to the lower dose.

“T2 lesion volume from baseline through week 48 was stable in patients who continued receiving frexalimab and decreased in placebo participants after switching to frexalimab at week 12,” Dr. Mao-Draayer reported.

The CD40-CD40L co-stimulatory pathway that regulates both adaptive and innate immune responses has been pursued as a target for MS therapies for decades, Dr. Mao-Draayer said.

A first-generation monoclonal antibody directed at elevated levels of CD40L, which is implicated in the inflammation that drives MS, showed promise but was abandoned after it was associated with an increased risk for thromboembolic events in a phase 1 trial, she said.

However, the second-generation agent was engineered to avoid an interaction with platelets, which played a role in the risk for thrombosis associated with the failure of the earlier drug.

As with the first-generation agent, frexalimab had little or no impact on lymphocyte count or immunoglobulin G and immunoglobulin M levels. Both remained stable during the 12-week controlled trial and through the ongoing open-label extension, Dr. Mao-Draayer said.

This might be a factor in the low level of adverse events. Most importantly, there have been no thromboembolic events associated with frexalimab so far, but the follow-up data also show rates of infection and other events, such as nasopharyngitis, that were comparable with placebo in the 12-week controlled trial and have not increased over longer-term monitoring.

Such adverse events as headache and COVID-19 infection have also occurred at rates similar to placebo.

Two phase 3 trials are underway. FREXALT is being conducted in relapsing-remitting MS. FREVIV has enrolled patients with nonrelapsing secondary progressive MS.
 

Impressively Low New Lesion Count

Commenting on the findings, Jeffrey Cohen, MD, director of the Mellen Center for Multiple Sclerosis, Cleveland Clinic, who was not involved in the research, said that over the course of the extended follow-up, MS activity in the central nervous system as measured with new Gd+ T1 lesions was impressively low. 

He noted that the phase 2 open-label follow-up continues to support the promise of frexalimab. But Dr. Cohen cautioned that this does not obviate the need for phase 3 data.

In particular, he said that an immunomodulatory agent that does not affect the lymphocyte count has a theoretical advantage, but pointed out that the benefit is still presumably mediated by blocking pathways that mediate autoimmune activity.

Even if lymphocyte count is unaffected, the immunomodulatory pathway by which frexalimab does exert its benefit might pose a different set of risks, he said.

“We will not have sufficient data to judge the promise of this agent until the phase 3 trials are completed,” he said.

Dr. Mao-Draayer reported financial relationships with Acorda, Bayer, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Horizon, Janssen, Novartis, Questor, Teva, and Sanofi, which provided funding for the phase 2 frexalimab trial. Dr. Cohen reported financial relationships with Astoria, Convelo, EMD Serono, FiND, INmune, and Sandoz.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — A second-generation anti-CD40L monoclonal antibody suppresses multiple sclerosis (MS) disease activity on MRI to an uncommonly high degree, new trial data suggested.

Researchers found a near absence of new brain lesions at 48 weeks in patients on the highest dose. At this level of disease suppression, there was no evidence of increased infection risk, which investigators said might relate to its mechanism of action. In addition, there were no thrombotic events, which is what defeated a first-generation drug in this same class.

Among those initially randomly assigned to receive 1200 mg every 4 weeks, 96% were free of new gadolinium-positive (Gd+ T1) lesions at 48 weeks, reported investigator Yang Mao-Draayer, MD, PhD, director of Clinical and Experimental Therapeutics at the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City. Annual relapse rates were also low.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
 

No Effect on Lymphocyte Count

As previously reported, 12-week frexalimab results were noteworthy because they provided validation for CD40L as a target in the control of MS. One of the unique features of this therapy relative to many other immunomodulatory therapies is that it has shown little, if any, effect on lymphocyte counts or immunoglobulin levels.

In the double-blind randomized phase 2 trial, 125 patients with MS of all other MS therapy were randomized in a 4:4:4:1 ratio to 1200-mg frexalimab administered intravenously every 4 weeks after a loading dose, to 300-mg frexalimab administered subcutaneously every 2 weeks after a loading dose, or to one of the two matching placebo arms.

For the primary endpoint of new Gd+ T1 lesions at the end of the blinded study, the rates at week 12 were 0.2 and 0.3 in the higher- and lower-dose treatment groups, respectively, and 1.4 in the pooled placebo groups.

At 48 weeks, the results were even better. From 12 weeks, the rate of Gd+ T1 lesions in the high-dose group continued to fall, reaching 0.1 at week 24 and 0.0 at week 48. In the lower-dose group, there was also a stepwise decline over time with a value of 0.2 at week 48. The annual relapse rate at week 48 was 0.4.
 

Reengineered Agent

In the placebo groups, the same type of suppression of disease activity was observed after they were switched to active therapy at the end of 12 weeks.

By 24 weeks, the number of new Gd+ T1 lesions had fallen to 0.3 in placebo patients switched to the higher dose and 1.0 in those switched to the lower dose.

By week 48, the rates were 0.2 in both of the switch arms.

The proportions of patients free of new Gd+ T1 lesions at 48 weeks were 96% in the group started and maintained on the highest dose of frexalimab, 87% in those started and maintained on the lower dose, 90% in those started on placebo and switched to the highest dose of frexalimab, and 92% of placebo patients switched to the lower dose.

“T2 lesion volume from baseline through week 48 was stable in patients who continued receiving frexalimab and decreased in placebo participants after switching to frexalimab at week 12,” Dr. Mao-Draayer reported.

The CD40-CD40L co-stimulatory pathway that regulates both adaptive and innate immune responses has been pursued as a target for MS therapies for decades, Dr. Mao-Draayer said.

A first-generation monoclonal antibody directed at elevated levels of CD40L, which is implicated in the inflammation that drives MS, showed promise but was abandoned after it was associated with an increased risk for thromboembolic events in a phase 1 trial, she said.

However, the second-generation agent was engineered to avoid an interaction with platelets, which played a role in the risk for thrombosis associated with the failure of the earlier drug.

As with the first-generation agent, frexalimab had little or no impact on lymphocyte count or immunoglobulin G and immunoglobulin M levels. Both remained stable during the 12-week controlled trial and through the ongoing open-label extension, Dr. Mao-Draayer said.

This might be a factor in the low level of adverse events. Most importantly, there have been no thromboembolic events associated with frexalimab so far, but the follow-up data also show rates of infection and other events, such as nasopharyngitis, that were comparable with placebo in the 12-week controlled trial and have not increased over longer-term monitoring.

Such adverse events as headache and COVID-19 infection have also occurred at rates similar to placebo.

Two phase 3 trials are underway. FREXALT is being conducted in relapsing-remitting MS. FREVIV has enrolled patients with nonrelapsing secondary progressive MS.
 

Impressively Low New Lesion Count

Commenting on the findings, Jeffrey Cohen, MD, director of the Mellen Center for Multiple Sclerosis, Cleveland Clinic, who was not involved in the research, said that over the course of the extended follow-up, MS activity in the central nervous system as measured with new Gd+ T1 lesions was impressively low. 

He noted that the phase 2 open-label follow-up continues to support the promise of frexalimab. But Dr. Cohen cautioned that this does not obviate the need for phase 3 data.

In particular, he said that an immunomodulatory agent that does not affect the lymphocyte count has a theoretical advantage, but pointed out that the benefit is still presumably mediated by blocking pathways that mediate autoimmune activity.

Even if lymphocyte count is unaffected, the immunomodulatory pathway by which frexalimab does exert its benefit might pose a different set of risks, he said.

“We will not have sufficient data to judge the promise of this agent until the phase 3 trials are completed,” he said.

Dr. Mao-Draayer reported financial relationships with Acorda, Bayer, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Horizon, Janssen, Novartis, Questor, Teva, and Sanofi, which provided funding for the phase 2 frexalimab trial. Dr. Cohen reported financial relationships with Astoria, Convelo, EMD Serono, FiND, INmune, and Sandoz.

A version of this article appeared on Medscape.com.

PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.

In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval^® by Merril Life Sciences and compared them with the balloon-expandable Sapien^® from Edwards Lifesciences and the self-expanding Evolut^® valve from Medtronic.

The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.

The platform with intermediate sizes provided a nonsignificant numerical advantage in both safety and efficacy over its rivals, Patrick W. Serruys, MD, PhD, from the Department of Cardiology at the University of Galway in Galway, Ireland, reported at the Congress of the European Association of Percutaneous Coronary Interventions 2024.

The LANDMARK Trial

The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.

Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.

The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.

Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.

For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.

When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms. 

Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.

Precise Matching

The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.

The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.

Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.

However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.

Longer Follow-Up to Come

Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.

Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”

And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.

A version of this article appeared on Medscape.com.

PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.

In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval^® by Merril Life Sciences and compared them with the balloon-expandable Sapien^® from Edwards Lifesciences and the self-expanding Evolut^® valve from Medtronic.

The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.

The platform with intermediate sizes provided a nonsignificant numerical advantage in both safety and efficacy over its rivals, Patrick W. Serruys, MD, PhD, from the Department of Cardiology at the University of Galway in Galway, Ireland, reported at the Congress of the European Association of Percutaneous Coronary Interventions 2024.

The LANDMARK Trial

The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.

Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.

The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.

Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.

For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.

When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms. 

Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.

Precise Matching

The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.

The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.

Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.

However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.

Longer Follow-Up to Come

Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.

Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”

And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.

A version of this article appeared on Medscape.com.

PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.

In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval^® by Merril Life Sciences and compared them with the balloon-expandable Sapien^® from Edwards Lifesciences and the self-expanding Evolut^® valve from Medtronic.

The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.

The platform with intermediate sizes provided a nonsignificant numerical advantage in both safety and efficacy over its rivals, Patrick W. Serruys, MD, PhD, from the Department of Cardiology at the University of Galway in Galway, Ireland, reported at the Congress of the European Association of Percutaneous Coronary Interventions 2024.

The LANDMARK Trial

The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.

Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.

The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.

Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.

For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.

When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms. 

Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.

Precise Matching

The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.

The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.

Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.

However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.

Longer Follow-Up to Come

Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.

Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”

And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.

A version of this article appeared on Medscape.com.

TORONTO — In the course of a well visit, the way in which clinicians elicit an adolescent’s sexual orientation and gender identity (SOGI) matters, and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.

In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.

Based on his work, there are two aims.

“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”

Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.

This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.

These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
 

Revealing Sensitive Information

With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).

The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.

These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.

The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.

“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.

The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.

For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.

For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.

As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.

In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.

When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.

“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
 

Protecting Patients

The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.

“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.

“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.

She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.

Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.

Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.

TORONTO — In the course of a well visit, the way in which clinicians elicit an adolescent’s sexual orientation and gender identity (SOGI) matters, and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.

In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.

Based on his work, there are two aims.

“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”

Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.

This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.

These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
 

Revealing Sensitive Information

With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).

The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.

These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.

The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.

“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.

The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.

For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.

For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.

As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.

In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.

When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.

“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
 

Protecting Patients

The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.

“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.

“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.

She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.

Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.

Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.

TORONTO — In the course of a well visit, the way in which clinicians elicit an adolescent’s sexual orientation and gender identity (SOGI) matters, and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.

In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.

Based on his work, there are two aims.

“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”

Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.

This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.

These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
 

Revealing Sensitive Information

With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).

The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.

These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.

The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.

“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.

The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.

For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.

For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.

As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.

In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.

When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.

“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
 

Protecting Patients

The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.

“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.

“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.

She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.

Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.

Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.