Rheumatology

Researchers have identified three distinct subgroups of Sjögren syndrome (SS) with different prognoses. While previous efforts to stratify these patients were based on reported symptoms, this new analysis is the first to add clinical and biological manifestations into the equation.

The three distinct patient clusters are those with B-cell active disease with low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). Each group had distinct long-term outcomes, including disease evolution and lymphoma incidence.

The findings were published in The Lancet Rheumatology.
 

Derived and Validated in Separate Cohorts

Researchers led by Yann Nguyen, MD, PhD, of Bicêtre Hospital and Paris-Saclay University, Paris, France, identified distinct subgroups with data from the French Paris-Saclay cohort, a group of patients suspected of having SS who participated in a multidisciplinary diagnostic session at a French National Referral Center for Rare Systemic Autoimmune Diseases and were recruited between 1999 and 2022.

The study included only patients who met the 2002 American-European Consensus Group criteria for SS and had European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scores at inclusion. Researchers excluded patients with other autoimmune diseases associated with SS.

Researchers identified distinct subgroups using 26 variables, including patient-reported symptoms, clinical parameters, and biological data.

Researchers then validated the subgroups using the same methodology in the Assessment of Systemic Signs and Evolution of Sjögren’s syndrome (ASSESS) cohort, a national French multicenter prospective cohort formed in 2006. They then compared changes in disease activity (measured by ESSDAI) and patient-acceptable symptom state (measured by ESSPRI) between the groups over 5 years of follow-up, as well as differences in lymphoma incidence over 15 years of follow-up.
 

Patients With High Systemic Disease, Low Symptoms Fare Worse

The study ultimately included 534 patients from the Paris-Saclay cohort and 395 patients from the ASSESS cohort. For both groups, 94% of patients were women, and the median age was between 53 and 54 years.

In the Paris-Saclay group, 205 patients were classified as BALS, 160 were HSA, and 169 were LSAHS. In the ASSESS cohort, BALS remained the largest group (186 patients), followed by HSA (158 patients). Only 51 patients in the second cohort were classified as LSAHS.

During 5 years of follow-up in the ASSESS cohort, systemic disease activity improved in the HSA cluster and worsened in the BALS cluster, while there were no significant changes in the LSAHS cluster. The BALS cluster was the only group to experience significant changes in patient-acceptable symptom states during follow-up: 49% of patients with BALS had an ESSPRI score of less than 5 at inclusion, but this percentage dipped to 36% at month 60.

The findings “highlight the fact that even in patients who present with predominantly systemic manifestations, the symptom burden is high and should not be neglected,” the authors wrote.

The three categories established in this study did not correlate well with previous symptom-based stratification of patients with SS, the authors noted, which looked at the five most common symptoms associated with the condition: Pain, fatigue, dryness, anxiety, and depression.

“Patients from the high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue subgroups were present in each of our three clusters,” they wrote. “This finding is consistent with the poor correlation between patient-reported outcomes and systemic disease activity.”

Lymphoma was diagnosed in 5 of 186 patients (3%) in the BALS cluster, diagnosed after a median of 70 months of follow-up, and 6 of 158 patients (4%) in the HSA cluster, diagnosed after a median of 23 months follow-up. There were no cases of lymphoma in the LSAHS group.

“Notably, in the BALS cluster, lymphoma occurred later than in the HSA cluster, and after 5 years, systemic manifestations in this cluster tended to be similar to those in the HSA cluster at inclusion,” the authors added. “The BALS cluster could therefore represent an earlier stage of the disease and carry the risk of progressing toward a more systemic phenotype.”
 

A ‘First Step’ to Subgrouping Patients

Alan Baer, MD, director of the Jerome Greene Sjogren’s Syndrome Center at John Hopkins Medical Center in Baltimore, Maryland, who commented on the study, noted that these three subgroups did “resonate” with what clinicians see in practice. Certain patients may have lab results that are “quite striking” even though they report minimal symptoms. The reverse is also true: Patients who have a high symptom burden without signs of systemic disease activity. Whether these patients should be managed differently “remains the key question,” he said.

“The hope is that when you have a group of patients that’s relatively homogenous in terms of their clinical features, that also translates to similarities into the underlying pathogenesis that can then lead to treatments that are targeted to specific subgroups of patients,” he added.

Another approach could be looking directly at molecular alterations across patients with SS and seeing how they correlate to clinical features, Dr. Baer noted.

This study “is a first step” in figuring out how to best define SS subgroups, he said, adding that “there’s more work to be done.”

This research was funded by the Fondation pour la Recherche Medicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology. The study authors disclosed financial relationships with various pharmaceutical companies. Dr. Baer had no relevant disclosures.

A version of this article appeared on Medscape.com .

Researchers have identified three distinct subgroups of Sjögren syndrome (SS) with different prognoses. While previous efforts to stratify these patients were based on reported symptoms, this new analysis is the first to add clinical and biological manifestations into the equation.

The three distinct patient clusters are those with B-cell active disease with low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). Each group had distinct long-term outcomes, including disease evolution and lymphoma incidence.

The findings were published in The Lancet Rheumatology.
 

Derived and Validated in Separate Cohorts

Researchers led by Yann Nguyen, MD, PhD, of Bicêtre Hospital and Paris-Saclay University, Paris, France, identified distinct subgroups with data from the French Paris-Saclay cohort, a group of patients suspected of having SS who participated in a multidisciplinary diagnostic session at a French National Referral Center for Rare Systemic Autoimmune Diseases and were recruited between 1999 and 2022.

The study included only patients who met the 2002 American-European Consensus Group criteria for SS and had European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scores at inclusion. Researchers excluded patients with other autoimmune diseases associated with SS.

Researchers identified distinct subgroups using 26 variables, including patient-reported symptoms, clinical parameters, and biological data.

Researchers then validated the subgroups using the same methodology in the Assessment of Systemic Signs and Evolution of Sjögren’s syndrome (ASSESS) cohort, a national French multicenter prospective cohort formed in 2006. They then compared changes in disease activity (measured by ESSDAI) and patient-acceptable symptom state (measured by ESSPRI) between the groups over 5 years of follow-up, as well as differences in lymphoma incidence over 15 years of follow-up.
 

Patients With High Systemic Disease, Low Symptoms Fare Worse

The study ultimately included 534 patients from the Paris-Saclay cohort and 395 patients from the ASSESS cohort. For both groups, 94% of patients were women, and the median age was between 53 and 54 years.

In the Paris-Saclay group, 205 patients were classified as BALS, 160 were HSA, and 169 were LSAHS. In the ASSESS cohort, BALS remained the largest group (186 patients), followed by HSA (158 patients). Only 51 patients in the second cohort were classified as LSAHS.

During 5 years of follow-up in the ASSESS cohort, systemic disease activity improved in the HSA cluster and worsened in the BALS cluster, while there were no significant changes in the LSAHS cluster. The BALS cluster was the only group to experience significant changes in patient-acceptable symptom states during follow-up: 49% of patients with BALS had an ESSPRI score of less than 5 at inclusion, but this percentage dipped to 36% at month 60.

The findings “highlight the fact that even in patients who present with predominantly systemic manifestations, the symptom burden is high and should not be neglected,” the authors wrote.

The three categories established in this study did not correlate well with previous symptom-based stratification of patients with SS, the authors noted, which looked at the five most common symptoms associated with the condition: Pain, fatigue, dryness, anxiety, and depression.

“Patients from the high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue subgroups were present in each of our three clusters,” they wrote. “This finding is consistent with the poor correlation between patient-reported outcomes and systemic disease activity.”

Lymphoma was diagnosed in 5 of 186 patients (3%) in the BALS cluster, diagnosed after a median of 70 months of follow-up, and 6 of 158 patients (4%) in the HSA cluster, diagnosed after a median of 23 months follow-up. There were no cases of lymphoma in the LSAHS group.

“Notably, in the BALS cluster, lymphoma occurred later than in the HSA cluster, and after 5 years, systemic manifestations in this cluster tended to be similar to those in the HSA cluster at inclusion,” the authors added. “The BALS cluster could therefore represent an earlier stage of the disease and carry the risk of progressing toward a more systemic phenotype.”
 

A ‘First Step’ to Subgrouping Patients

Alan Baer, MD, director of the Jerome Greene Sjogren’s Syndrome Center at John Hopkins Medical Center in Baltimore, Maryland, who commented on the study, noted that these three subgroups did “resonate” with what clinicians see in practice. Certain patients may have lab results that are “quite striking” even though they report minimal symptoms. The reverse is also true: Patients who have a high symptom burden without signs of systemic disease activity. Whether these patients should be managed differently “remains the key question,” he said.

“The hope is that when you have a group of patients that’s relatively homogenous in terms of their clinical features, that also translates to similarities into the underlying pathogenesis that can then lead to treatments that are targeted to specific subgroups of patients,” he added.

Another approach could be looking directly at molecular alterations across patients with SS and seeing how they correlate to clinical features, Dr. Baer noted.

This study “is a first step” in figuring out how to best define SS subgroups, he said, adding that “there’s more work to be done.”

This research was funded by the Fondation pour la Recherche Medicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology. The study authors disclosed financial relationships with various pharmaceutical companies. Dr. Baer had no relevant disclosures.

A version of this article appeared on Medscape.com .

Researchers have identified three distinct subgroups of Sjögren syndrome (SS) with different prognoses. While previous efforts to stratify these patients were based on reported symptoms, this new analysis is the first to add clinical and biological manifestations into the equation.

The three distinct patient clusters are those with B-cell active disease with low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). Each group had distinct long-term outcomes, including disease evolution and lymphoma incidence.

The findings were published in The Lancet Rheumatology.
 

Derived and Validated in Separate Cohorts

Researchers led by Yann Nguyen, MD, PhD, of Bicêtre Hospital and Paris-Saclay University, Paris, France, identified distinct subgroups with data from the French Paris-Saclay cohort, a group of patients suspected of having SS who participated in a multidisciplinary diagnostic session at a French National Referral Center for Rare Systemic Autoimmune Diseases and were recruited between 1999 and 2022.

The study included only patients who met the 2002 American-European Consensus Group criteria for SS and had European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scores at inclusion. Researchers excluded patients with other autoimmune diseases associated with SS.

Researchers identified distinct subgroups using 26 variables, including patient-reported symptoms, clinical parameters, and biological data.

Researchers then validated the subgroups using the same methodology in the Assessment of Systemic Signs and Evolution of Sjögren’s syndrome (ASSESS) cohort, a national French multicenter prospective cohort formed in 2006. They then compared changes in disease activity (measured by ESSDAI) and patient-acceptable symptom state (measured by ESSPRI) between the groups over 5 years of follow-up, as well as differences in lymphoma incidence over 15 years of follow-up.
 

Patients With High Systemic Disease, Low Symptoms Fare Worse

The study ultimately included 534 patients from the Paris-Saclay cohort and 395 patients from the ASSESS cohort. For both groups, 94% of patients were women, and the median age was between 53 and 54 years.

In the Paris-Saclay group, 205 patients were classified as BALS, 160 were HSA, and 169 were LSAHS. In the ASSESS cohort, BALS remained the largest group (186 patients), followed by HSA (158 patients). Only 51 patients in the second cohort were classified as LSAHS.

During 5 years of follow-up in the ASSESS cohort, systemic disease activity improved in the HSA cluster and worsened in the BALS cluster, while there were no significant changes in the LSAHS cluster. The BALS cluster was the only group to experience significant changes in patient-acceptable symptom states during follow-up: 49% of patients with BALS had an ESSPRI score of less than 5 at inclusion, but this percentage dipped to 36% at month 60.

The findings “highlight the fact that even in patients who present with predominantly systemic manifestations, the symptom burden is high and should not be neglected,” the authors wrote.

The three categories established in this study did not correlate well with previous symptom-based stratification of patients with SS, the authors noted, which looked at the five most common symptoms associated with the condition: Pain, fatigue, dryness, anxiety, and depression.

“Patients from the high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue subgroups were present in each of our three clusters,” they wrote. “This finding is consistent with the poor correlation between patient-reported outcomes and systemic disease activity.”

Lymphoma was diagnosed in 5 of 186 patients (3%) in the BALS cluster, diagnosed after a median of 70 months of follow-up, and 6 of 158 patients (4%) in the HSA cluster, diagnosed after a median of 23 months follow-up. There were no cases of lymphoma in the LSAHS group.

“Notably, in the BALS cluster, lymphoma occurred later than in the HSA cluster, and after 5 years, systemic manifestations in this cluster tended to be similar to those in the HSA cluster at inclusion,” the authors added. “The BALS cluster could therefore represent an earlier stage of the disease and carry the risk of progressing toward a more systemic phenotype.”
 

A ‘First Step’ to Subgrouping Patients

Alan Baer, MD, director of the Jerome Greene Sjogren’s Syndrome Center at John Hopkins Medical Center in Baltimore, Maryland, who commented on the study, noted that these three subgroups did “resonate” with what clinicians see in practice. Certain patients may have lab results that are “quite striking” even though they report minimal symptoms. The reverse is also true: Patients who have a high symptom burden without signs of systemic disease activity. Whether these patients should be managed differently “remains the key question,” he said.

“The hope is that when you have a group of patients that’s relatively homogenous in terms of their clinical features, that also translates to similarities into the underlying pathogenesis that can then lead to treatments that are targeted to specific subgroups of patients,” he added.

Another approach could be looking directly at molecular alterations across patients with SS and seeing how they correlate to clinical features, Dr. Baer noted.

This study “is a first step” in figuring out how to best define SS subgroups, he said, adding that “there’s more work to be done.”

This research was funded by the Fondation pour la Recherche Medicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology. The study authors disclosed financial relationships with various pharmaceutical companies. Dr. Baer had no relevant disclosures.

A version of this article appeared on Medscape.com .

Physiotherapy conducted via video conference is noninferior to in-person sessions for the treatment of chronic knee pain, according to new research.

In the trial, participants assigned to in-person or telehealth sessions had similar improvements in knee pain and physical function over 3 months, while the online group had better session attendance and reported higher convenience.

While the COVID-19 pandemic increased the use of telerehabilitation physiotherapy services, it is not clear how these teleservices will be utilized moving forward, the study authors wrote. There is some research suggesting that both in-person and online physiotherapy are equally effective, but surveys suggest that both providers and patients remain unconvinced.

“Based on pandemic telerehabilitation experiences, less than half of allied health clinicians believe telerehabilitation is as effective as in-person care and almost half of patients think video conferencing with a physiotherapist provides lower quality care,” study first author Rana Hinman, PhD, professor of physiotherapy at the University of Melbourne, Australia, and colleagues wrote in their report published online in The Lancet.
 

‘A Game Changer’ for Physical Therapy

Commenting on the study for this news organization, Daniel White, ScD, an associate professor in the department of physical therapy at the University of Delaware in Newark, Delaware, called the research “a game changer” for physical therapy. 

“It’s showing that in-person care can be replicated in terms of efficacy,” in telehealth settings, he said. “From a telehealth perspective, it really opens the doors to access to people who have difficulty reaching physical therapists,” he added, “and puts us on stage with other modes of telehealth that are given as part of modern medicine.”

Dr. White noted that physical therapy treatment for knee osteoarthritis is underused, with just 10% of patients seeing a physical therapist prior to undergoing knee replacement. While knee replacements are effective interventions, he said, access to physical therapy could allow many patients to put off having surgery.

The findings not only provide solutions for access issues but also assuage concerns “that you’re going to get ‘physical therapy lite’” with telehealth, Dr. White added. 

“You can deliver physical therapy to this group that typically is not getting enough of it,” he said, “and it is just as effective when delivered online than if it were to be delivered in person.”
 

Noninferiority Maintained at 9 Months’ Follow-up

To understand how video conferencing physiotherapy consultations compared to in-person care, the researchers designed a non-inferiority randomized controlled trial. 

For the trial, researchers enrolled 394 adults with chronic knee pain who were aged ≥ 45 years, had activity-related joint pain, and either had no morning stiffness or morning stiffness lasting < 30 minutes. Other inclusion criteria were history of knee pain of ≥ 3 months, knee pain most days of the previous month, average walking pain score of four or more on the 11-point numeric rating scale (NRS) over the previous week, and difficulty walking and climbing stairs.

Participants also needed access to a computer device with internet as well as the ability to travel to the nearest trial physiotherapist.

The study recruited 15 physiotherapists across 27 practices in metropolitan Queensland and Victoria, Australia, of which 60% had no previous telerehabilitation experience. Physiotherapists were trained to conduct video sessions via e-learning, practice video consultations, and a competency video conferencing evaluation.

Participants were randomly assigned to in-person or video physiotherapist consultations, with both groups receiving five consultations over 3 months. All clients were prescribed a home-based strength training program and physical activity plan.

The primary outcomes were changes at 3 months in patient-reported knee pain (on a scale of 0-10), with an inferiority margin of 0.95, and physical function — assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) — with an inferiority margin of −5.44.

From December 10, 2019, to June 17, 2022, 204 participants were assigned to in-person sessions and 190 were assigned to telerehabilitation. At 3 months, both groups reported improved pain and physical function, with no significant differences between the two groups with either measure. The mean between-group difference was 0.16 (95% CI, −0.26 to 0.57) for knee pain and 1.65 (−0.23 to 3.53) for physical function. Noninferiority was also maintained at 9 months’ follow-up.

The trial took place over the COVID-19 pandemic, which limited participant ability to attend in-person consultations. In total, 84% of participants assigned to in-person rehabilitation attended at least three or more consultations compared with 96% of those assigned to telerehabilitation. In an additional analysis including only participants attending three or more sessions, improvement in knee pain and physical function was similar between the in-person or tele-rehabilitation groups “showing that the findings are robust,” the authors noted.

At 3 months, the telerehabilitation group ranked their sessions as more convenient that their in-person counterparts and reported greater adherence to their strengthening program. At 9 months’ follow-up, the telerehabilitation group had higher physical activity scores than the in-person group.

This research was funded by the Australian National Health and Medical Research Council. Two authors reported grant funding paid to the University of Melbourne from the National Health & Medical Research Council, Australian Research Council, Medical Research Future Fund, and Medibank for research. Dr. White has been a paid speaker for Viatris.

A version of this article appeared on Medscape.com.

Physiotherapy conducted via video conference is noninferior to in-person sessions for the treatment of chronic knee pain, according to new research.

In the trial, participants assigned to in-person or telehealth sessions had similar improvements in knee pain and physical function over 3 months, while the online group had better session attendance and reported higher convenience.

While the COVID-19 pandemic increased the use of telerehabilitation physiotherapy services, it is not clear how these teleservices will be utilized moving forward, the study authors wrote. There is some research suggesting that both in-person and online physiotherapy are equally effective, but surveys suggest that both providers and patients remain unconvinced.

“Based on pandemic telerehabilitation experiences, less than half of allied health clinicians believe telerehabilitation is as effective as in-person care and almost half of patients think video conferencing with a physiotherapist provides lower quality care,” study first author Rana Hinman, PhD, professor of physiotherapy at the University of Melbourne, Australia, and colleagues wrote in their report published online in The Lancet.
 

‘A Game Changer’ for Physical Therapy

Commenting on the study for this news organization, Daniel White, ScD, an associate professor in the department of physical therapy at the University of Delaware in Newark, Delaware, called the research “a game changer” for physical therapy. 

“It’s showing that in-person care can be replicated in terms of efficacy,” in telehealth settings, he said. “From a telehealth perspective, it really opens the doors to access to people who have difficulty reaching physical therapists,” he added, “and puts us on stage with other modes of telehealth that are given as part of modern medicine.”

Dr. White noted that physical therapy treatment for knee osteoarthritis is underused, with just 10% of patients seeing a physical therapist prior to undergoing knee replacement. While knee replacements are effective interventions, he said, access to physical therapy could allow many patients to put off having surgery.

The findings not only provide solutions for access issues but also assuage concerns “that you’re going to get ‘physical therapy lite’” with telehealth, Dr. White added. 

“You can deliver physical therapy to this group that typically is not getting enough of it,” he said, “and it is just as effective when delivered online than if it were to be delivered in person.”
 

Noninferiority Maintained at 9 Months’ Follow-up

To understand how video conferencing physiotherapy consultations compared to in-person care, the researchers designed a non-inferiority randomized controlled trial. 

For the trial, researchers enrolled 394 adults with chronic knee pain who were aged ≥ 45 years, had activity-related joint pain, and either had no morning stiffness or morning stiffness lasting < 30 minutes. Other inclusion criteria were history of knee pain of ≥ 3 months, knee pain most days of the previous month, average walking pain score of four or more on the 11-point numeric rating scale (NRS) over the previous week, and difficulty walking and climbing stairs.

Participants also needed access to a computer device with internet as well as the ability to travel to the nearest trial physiotherapist.

The study recruited 15 physiotherapists across 27 practices in metropolitan Queensland and Victoria, Australia, of which 60% had no previous telerehabilitation experience. Physiotherapists were trained to conduct video sessions via e-learning, practice video consultations, and a competency video conferencing evaluation.

Participants were randomly assigned to in-person or video physiotherapist consultations, with both groups receiving five consultations over 3 months. All clients were prescribed a home-based strength training program and physical activity plan.

The primary outcomes were changes at 3 months in patient-reported knee pain (on a scale of 0-10), with an inferiority margin of 0.95, and physical function — assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) — with an inferiority margin of −5.44.

From December 10, 2019, to June 17, 2022, 204 participants were assigned to in-person sessions and 190 were assigned to telerehabilitation. At 3 months, both groups reported improved pain and physical function, with no significant differences between the two groups with either measure. The mean between-group difference was 0.16 (95% CI, −0.26 to 0.57) for knee pain and 1.65 (−0.23 to 3.53) for physical function. Noninferiority was also maintained at 9 months’ follow-up.

The trial took place over the COVID-19 pandemic, which limited participant ability to attend in-person consultations. In total, 84% of participants assigned to in-person rehabilitation attended at least three or more consultations compared with 96% of those assigned to telerehabilitation. In an additional analysis including only participants attending three or more sessions, improvement in knee pain and physical function was similar between the in-person or tele-rehabilitation groups “showing that the findings are robust,” the authors noted.

At 3 months, the telerehabilitation group ranked their sessions as more convenient that their in-person counterparts and reported greater adherence to their strengthening program. At 9 months’ follow-up, the telerehabilitation group had higher physical activity scores than the in-person group.

This research was funded by the Australian National Health and Medical Research Council. Two authors reported grant funding paid to the University of Melbourne from the National Health & Medical Research Council, Australian Research Council, Medical Research Future Fund, and Medibank for research. Dr. White has been a paid speaker for Viatris.

A version of this article appeared on Medscape.com.

Physiotherapy conducted via video conference is noninferior to in-person sessions for the treatment of chronic knee pain, according to new research.

In the trial, participants assigned to in-person or telehealth sessions had similar improvements in knee pain and physical function over 3 months, while the online group had better session attendance and reported higher convenience.

While the COVID-19 pandemic increased the use of telerehabilitation physiotherapy services, it is not clear how these teleservices will be utilized moving forward, the study authors wrote. There is some research suggesting that both in-person and online physiotherapy are equally effective, but surveys suggest that both providers and patients remain unconvinced.

“Based on pandemic telerehabilitation experiences, less than half of allied health clinicians believe telerehabilitation is as effective as in-person care and almost half of patients think video conferencing with a physiotherapist provides lower quality care,” study first author Rana Hinman, PhD, professor of physiotherapy at the University of Melbourne, Australia, and colleagues wrote in their report published online in The Lancet.
 

‘A Game Changer’ for Physical Therapy

Commenting on the study for this news organization, Daniel White, ScD, an associate professor in the department of physical therapy at the University of Delaware in Newark, Delaware, called the research “a game changer” for physical therapy. 

“It’s showing that in-person care can be replicated in terms of efficacy,” in telehealth settings, he said. “From a telehealth perspective, it really opens the doors to access to people who have difficulty reaching physical therapists,” he added, “and puts us on stage with other modes of telehealth that are given as part of modern medicine.”

Dr. White noted that physical therapy treatment for knee osteoarthritis is underused, with just 10% of patients seeing a physical therapist prior to undergoing knee replacement. While knee replacements are effective interventions, he said, access to physical therapy could allow many patients to put off having surgery.

The findings not only provide solutions for access issues but also assuage concerns “that you’re going to get ‘physical therapy lite’” with telehealth, Dr. White added. 

“You can deliver physical therapy to this group that typically is not getting enough of it,” he said, “and it is just as effective when delivered online than if it were to be delivered in person.”
 

Noninferiority Maintained at 9 Months’ Follow-up

To understand how video conferencing physiotherapy consultations compared to in-person care, the researchers designed a non-inferiority randomized controlled trial. 

For the trial, researchers enrolled 394 adults with chronic knee pain who were aged ≥ 45 years, had activity-related joint pain, and either had no morning stiffness or morning stiffness lasting < 30 minutes. Other inclusion criteria were history of knee pain of ≥ 3 months, knee pain most days of the previous month, average walking pain score of four or more on the 11-point numeric rating scale (NRS) over the previous week, and difficulty walking and climbing stairs.

Participants also needed access to a computer device with internet as well as the ability to travel to the nearest trial physiotherapist.

The study recruited 15 physiotherapists across 27 practices in metropolitan Queensland and Victoria, Australia, of which 60% had no previous telerehabilitation experience. Physiotherapists were trained to conduct video sessions via e-learning, practice video consultations, and a competency video conferencing evaluation.

Participants were randomly assigned to in-person or video physiotherapist consultations, with both groups receiving five consultations over 3 months. All clients were prescribed a home-based strength training program and physical activity plan.

The primary outcomes were changes at 3 months in patient-reported knee pain (on a scale of 0-10), with an inferiority margin of 0.95, and physical function — assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) — with an inferiority margin of −5.44.

From December 10, 2019, to June 17, 2022, 204 participants were assigned to in-person sessions and 190 were assigned to telerehabilitation. At 3 months, both groups reported improved pain and physical function, with no significant differences between the two groups with either measure. The mean between-group difference was 0.16 (95% CI, −0.26 to 0.57) for knee pain and 1.65 (−0.23 to 3.53) for physical function. Noninferiority was also maintained at 9 months’ follow-up.

The trial took place over the COVID-19 pandemic, which limited participant ability to attend in-person consultations. In total, 84% of participants assigned to in-person rehabilitation attended at least three or more consultations compared with 96% of those assigned to telerehabilitation. In an additional analysis including only participants attending three or more sessions, improvement in knee pain and physical function was similar between the in-person or tele-rehabilitation groups “showing that the findings are robust,” the authors noted.

At 3 months, the telerehabilitation group ranked their sessions as more convenient that their in-person counterparts and reported greater adherence to their strengthening program. At 9 months’ follow-up, the telerehabilitation group had higher physical activity scores than the in-person group.

This research was funded by the Australian National Health and Medical Research Council. Two authors reported grant funding paid to the University of Melbourne from the National Health & Medical Research Council, Australian Research Council, Medical Research Future Fund, and Medibank for research. Dr. White has been a paid speaker for Viatris.

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment of patients with rheumatoid arthritis (RA) with non–tumor necrosis factor inhibitor (TNFi) biologic disease-modifying antirheumatic drugs (bDMARDs) may not pose an increased risk for cancer, compared with TNFis and conventional synthetic DMARDs.

METHODOLOGY:

• Previous research has presented conflicting results on the association between non-TNFi bDMARDs and the risk for cancer, with abatacept drawing particular attention owing to its mode of action.
• By utilizing information from Danish registers (January 2006-December 2020), researchers compared the risk for cancer in 14,944 patients with RA (age > 18 years) who were initiated on non-TNFi bDMARDs (tocilizumab/sarilumab, abatacept, or rituximab), TNFis, or were in the conventional synthetic DMARDs (bDMARD-naive) group.
• The patient population contributed to 21,982 treatment initiations, which corresponded to 1457, 1016, 690, 7458, and 11,361 treatment initiations for the tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive groups, respectively.
• Patients were followed up until a diagnosis was obtained for cancer, death, emigration, the initiation of a different bDMARD or a targeted synthetic DMARD, or the end of the study, whichever was earlier.
• The primary outcome was defined as any primary cancer diagnosis (except nonmelanoma skin cancer).

TAKEAWAY:

• The risk for overall cancer was not significantly higher in the tocilizumab/sarilumab-, abatacept-, or rituximab-initiated groups than in the TNFi-treated and bDMARD-naive groups.

• The likelihood of cancer appeared to be higher in patients with more than 5 years of exposure to abatacept than in the TNFi-treated (hazard ratio [HR], 1.41; 95% CI, 0.60-2.60) and bDMARD-naive groups (HR, 1.14; 95% CI, 0.51-2.33). However, the results were not statistically significant.
• Treatment with rituximab may be associated with a lower risk for hematologic cancers than for TNFi-treated (HR, 0.09; 95% CI, 0.00-2.06) or bDMARD-naive groups (HR, 0.13; 95% CI, 0.00-1.89), although the findings did not show statistical significance.

IN PRACTICE:

The authors wrote, “bDMARD-associated cancer risk remains a clinically important research question, and more future studies specifically investigating non-TNFi bDMARDs in terms of cancer risk in patients with RA are warranted.”

SOURCE:

The investigation, led by Rasmus Westermann, MD, of Aalborg University Hospital, Aalborg, Denmark, was published online on March 7 in Rheumatology.

LIMITATIONS:

Many patients received more than one type of non-TNFi bDMARD treatment during the study. Because the temporal relationship of DMARD treatment with cancer was not certain, potential carcinogenic treatment effects could not be distinguished. Limited data were available on cancer risk factors.

DISCLOSURES:

The study was supported by the Danish Rheumatism Association and the Danish Cancer Society. Some authors reported financial relationships with pharmaceutical companies outside of the submitted work.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment of patients with rheumatoid arthritis (RA) with non–tumor necrosis factor inhibitor (TNFi) biologic disease-modifying antirheumatic drugs (bDMARDs) may not pose an increased risk for cancer, compared with TNFis and conventional synthetic DMARDs.

METHODOLOGY:

• Previous research has presented conflicting results on the association between non-TNFi bDMARDs and the risk for cancer, with abatacept drawing particular attention owing to its mode of action.
• By utilizing information from Danish registers (January 2006-December 2020), researchers compared the risk for cancer in 14,944 patients with RA (age > 18 years) who were initiated on non-TNFi bDMARDs (tocilizumab/sarilumab, abatacept, or rituximab), TNFis, or were in the conventional synthetic DMARDs (bDMARD-naive) group.
• The patient population contributed to 21,982 treatment initiations, which corresponded to 1457, 1016, 690, 7458, and 11,361 treatment initiations for the tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive groups, respectively.
• Patients were followed up until a diagnosis was obtained for cancer, death, emigration, the initiation of a different bDMARD or a targeted synthetic DMARD, or the end of the study, whichever was earlier.
• The primary outcome was defined as any primary cancer diagnosis (except nonmelanoma skin cancer).

TAKEAWAY:

• The risk for overall cancer was not significantly higher in the tocilizumab/sarilumab-, abatacept-, or rituximab-initiated groups than in the TNFi-treated and bDMARD-naive groups.

• The likelihood of cancer appeared to be higher in patients with more than 5 years of exposure to abatacept than in the TNFi-treated (hazard ratio [HR], 1.41; 95% CI, 0.60-2.60) and bDMARD-naive groups (HR, 1.14; 95% CI, 0.51-2.33). However, the results were not statistically significant.
• Treatment with rituximab may be associated with a lower risk for hematologic cancers than for TNFi-treated (HR, 0.09; 95% CI, 0.00-2.06) or bDMARD-naive groups (HR, 0.13; 95% CI, 0.00-1.89), although the findings did not show statistical significance.

IN PRACTICE:

The authors wrote, “bDMARD-associated cancer risk remains a clinically important research question, and more future studies specifically investigating non-TNFi bDMARDs in terms of cancer risk in patients with RA are warranted.”

SOURCE:

The investigation, led by Rasmus Westermann, MD, of Aalborg University Hospital, Aalborg, Denmark, was published online on March 7 in Rheumatology.

LIMITATIONS:

Many patients received more than one type of non-TNFi bDMARD treatment during the study. Because the temporal relationship of DMARD treatment with cancer was not certain, potential carcinogenic treatment effects could not be distinguished. Limited data were available on cancer risk factors.

DISCLOSURES:

The study was supported by the Danish Rheumatism Association and the Danish Cancer Society. Some authors reported financial relationships with pharmaceutical companies outside of the submitted work.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Treatment of patients with rheumatoid arthritis (RA) with non–tumor necrosis factor inhibitor (TNFi) biologic disease-modifying antirheumatic drugs (bDMARDs) may not pose an increased risk for cancer, compared with TNFis and conventional synthetic DMARDs.

METHODOLOGY:

• Previous research has presented conflicting results on the association between non-TNFi bDMARDs and the risk for cancer, with abatacept drawing particular attention owing to its mode of action.
• By utilizing information from Danish registers (January 2006-December 2020), researchers compared the risk for cancer in 14,944 patients with RA (age > 18 years) who were initiated on non-TNFi bDMARDs (tocilizumab/sarilumab, abatacept, or rituximab), TNFis, or were in the conventional synthetic DMARDs (bDMARD-naive) group.
• The patient population contributed to 21,982 treatment initiations, which corresponded to 1457, 1016, 690, 7458, and 11,361 treatment initiations for the tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive groups, respectively.
• Patients were followed up until a diagnosis was obtained for cancer, death, emigration, the initiation of a different bDMARD or a targeted synthetic DMARD, or the end of the study, whichever was earlier.
• The primary outcome was defined as any primary cancer diagnosis (except nonmelanoma skin cancer).

TAKEAWAY:

• The risk for overall cancer was not significantly higher in the tocilizumab/sarilumab-, abatacept-, or rituximab-initiated groups than in the TNFi-treated and bDMARD-naive groups.

• The likelihood of cancer appeared to be higher in patients with more than 5 years of exposure to abatacept than in the TNFi-treated (hazard ratio [HR], 1.41; 95% CI, 0.60-2.60) and bDMARD-naive groups (HR, 1.14; 95% CI, 0.51-2.33). However, the results were not statistically significant.
• Treatment with rituximab may be associated with a lower risk for hematologic cancers than for TNFi-treated (HR, 0.09; 95% CI, 0.00-2.06) or bDMARD-naive groups (HR, 0.13; 95% CI, 0.00-1.89), although the findings did not show statistical significance.

IN PRACTICE:

The authors wrote, “bDMARD-associated cancer risk remains a clinically important research question, and more future studies specifically investigating non-TNFi bDMARDs in terms of cancer risk in patients with RA are warranted.”

SOURCE:

The investigation, led by Rasmus Westermann, MD, of Aalborg University Hospital, Aalborg, Denmark, was published online on March 7 in Rheumatology.

LIMITATIONS:

Many patients received more than one type of non-TNFi bDMARD treatment during the study. Because the temporal relationship of DMARD treatment with cancer was not certain, potential carcinogenic treatment effects could not be distinguished. Limited data were available on cancer risk factors.

DISCLOSURES:

The study was supported by the Danish Rheumatism Association and the Danish Cancer Society. Some authors reported financial relationships with pharmaceutical companies outside of the submitted work.
 

A version of this article appeared on Medscape.com.

Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.

The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.

McGill University

“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
 

Symptom Clusters in RA

In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.

Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.

In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.

Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).

Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.

Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.

The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
 

Patients With Depression Report Worse Disease Activity

In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.

The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.

From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.

In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.

While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.

Dr. Hepworth presented the findings on March 1.

Dr. Elliot Hepworth

The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.

“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
 

Some Disagreement, Same Takeaway

Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”

Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.

“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”

This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.

“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”

The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.

Dr. Sibel Aydin

“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”

“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”

CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.

The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.

McGill University

“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
 

Symptom Clusters in RA

In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.

Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.

In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.

Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).

Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.

Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.

The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
 

Patients With Depression Report Worse Disease Activity

In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.

The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.

From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.

In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.

While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.

Dr. Hepworth presented the findings on March 1.

Dr. Elliot Hepworth

The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.

“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
 

Some Disagreement, Same Takeaway

Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”

Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.

“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”

This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.

“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”

The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.

Dr. Sibel Aydin

“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”

“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”

CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.

The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.

McGill University

“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
 

Symptom Clusters in RA

In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.

Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.

In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.

Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).

Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.

Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.

The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
 

Patients With Depression Report Worse Disease Activity

In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.

The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.

From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.

In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.

While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.

Dr. Hepworth presented the findings on March 1.

Dr. Elliot Hepworth

The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.

“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
 

Some Disagreement, Same Takeaway

Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”

Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.

“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”

This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.

“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”

The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.

Dr. Sibel Aydin

“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”

“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”

CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.

A version of this article appeared on Medscape.com .

The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.

This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 

Wikimedia Commons/FitzColinGerald/Creative Commons License

Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:

• Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
• Adults with giant cell arteritis
• Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
• Patients aged 2 years or older with active systemic juvenile idiopathic arthritis

“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.

The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.

Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector. 

The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.

Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.

“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.

This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 

Wikimedia Commons/FitzColinGerald/Creative Commons License

Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:

• Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
• Adults with giant cell arteritis
• Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
• Patients aged 2 years or older with active systemic juvenile idiopathic arthritis

“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.

The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.

Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector. 

The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.

Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.

“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.

This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 

Wikimedia Commons/FitzColinGerald/Creative Commons License

Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:

• Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
• Adults with giant cell arteritis
• Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
• Patients aged 2 years or older with active systemic juvenile idiopathic arthritis

“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.

The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.

Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector. 

The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.

Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.

“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
 

A version of this article appeared on Medscape.com.

The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”

Yet should it have been? Is it worth another look today?

Courtesy Michael Pollard

At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.

“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”

“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
 

Key Findings Over the Years in RA

Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.

“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.

Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.

Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.

Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”

But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.

“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”

However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.

He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.

The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”

A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”

Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”

Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.

Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.

Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
 

Loading vs Not Loading, and Its Role in PsA and Other Diseases

“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.

“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”

In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.

However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.

More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.

In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”

And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”

In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.

Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.

The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”

Yet should it have been? Is it worth another look today?

Courtesy Michael Pollard

At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.

“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”

“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
 

Key Findings Over the Years in RA

Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.

“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.

Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.

Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.

Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”

But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.

“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”

However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.

He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.

The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”

A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”

Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”

Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.

Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.

Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
 

Loading vs Not Loading, and Its Role in PsA and Other Diseases

“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.

“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”

In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.

However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.

More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.

In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”

And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”

In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.

Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.

The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”

Yet should it have been? Is it worth another look today?

Courtesy Michael Pollard

At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.

“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”

“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
 

Key Findings Over the Years in RA

Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.

“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.

Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.

Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.

Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”

But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.

“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”

However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.

He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.

The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”

A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”

Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”

Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.

Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.

Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
 

Loading vs Not Loading, and Its Role in PsA and Other Diseases

“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.

“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”

In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.

However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.

More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.

In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”

And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”

In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.

Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

In patients with type 2 diabetes, there was no difference in risk of developing autoimmune disease if prescribed glucagon-like peptide 1 receptor agonists (GLP-1-RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

METHODOLOGY:

• The effect of GLP-1-RAs and SGLT2 inhibitors on autoimmune rheumatic disease (ARD) is understudied, though previous case reports and one study have hinted at increased risk.
• Researchers used administrative health data from 2014 to 2021 to identify 34,400 patients prescribed GLP-1-RAs and 83,500 patients prescribed SGLT2 inhibitors.
• They compared patients prescribed GLP-1-RAs or SGLT2 inhibitors with 68,400 patients prescribed DPP-4 inhibitors, which previous studies suggest do not increase ARD risk.
• Primary outcome was ARD incidence, defined by diagnostic codes.

TAKEAWAY:

• There were no significant differences in incident ARDs between the three groups.
• Mean follow-up time was 0.88-1.53 years.
• The hazard ratio (HR) for developing ARDs with GLP-1-RAs exposure was 0.93 (95% CI, 0.66-1.30) compared with DPP-4 inhibitors.
• The HR for developing ARDs with SGLT2 inhibitor exposure was 0.97 (95% CI, 0.76-1.24).

IN PRACTICE: 

“Extended longitudinal data are needed to assess risk and benefit with longer-term exposure,” the authors wrote.

SOURCE: 

First author Derin Karacabeyli, MD, of the University of British Columbia, Vancouver, Canada, presented the study in abstract form at the Canadian Rheumatology Association (CRA) 2024 Annual Meeting in Winnipeg on February 29.

LIMITATIONS: 

The study was observational, which could have some residual or unmeasured confounding of data. The researchers relied on diagnostic codes and the average follow-up time was short. 

DISCLOSURES:

The study was funded by the Canadian Institutes of Health Research. The authors had no disclosures.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).

The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February. 

The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.

Wyost (120-mg/1.7-mL injection) is approved to:

• Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy

Jubbonti (60-mg/1-mL injection) is approved to:

• Treat postmenopausal women with osteoporosis who are at high risk for fracture
• Increase bone mass in men with osteoporosis who are at high risk for fracture
• Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
• Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.

Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.

Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”

A version of this article appeared on Medscape.com.

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.