Psoriatic Arthritis

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

CLEVELAND – Patients with axial spondyloarthritis or psoriatic arthritis who used Janus kinase (JAK) inhibitors did not have higher risk of myocardial infarction, stroke, or venous thromboembolism (VTE), compared with those who used tumor necrosis factor inhibitors (TNFi), according to new research.

The information was presented in a poster at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

Patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) have increased cardiovascular risk compared with the general population. Emerging evidence has suggested that TNFi may protect the cardiovascular system and that there are cardiovascular and thrombotic concerns with JAK inhibitors.

Sali Merjanah, MD, a rheumatology fellow at Boston University, and colleagues, compared how drugs in the two treatment classes affected the likelihood of major adverse cardiovascular events (MACE) or VTE. MACE in this study were myocardial infarction and stroke.

In a search of the Marketscan Database during 2006-2021, the researchers identified 1,621 TNFi and 47 JAK inhibitor users with 273 and 8 cases of MACE, respectively. They identified 2,507 TNFi and 96 JAK users with 452 and 26 cases of VTE, respectively. Patients were aged 18-65 years and had at least one inpatient or two outpatient axSpA or PsA ICD-9 or ICD-10 diagnosis codes separated by at least 7 days.

The likelihood of MACE was 14% lower among JAK inhibitor users than TNFi users (the reference group), whereas the likelihood of VTE was 39% higher for JAK inhibitor users, but neither comparison was statistically significant. JAK/TNFi nonusers had a statistically significant 27% greater likelihood of MACE than did TNFi users. The likelihood for VTE was 12% higher for JAK/TNFi nonusers, compared with TNFi users, but this finding was not statistically significant. The researchers adjusted comparisons for age, medications, and comorbidities.
 

Small numbers complicate the research

Lianne Gensler, MD, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco, who was not part of the study, said the limitations the authors list are important to note. The researchers said that the study’s small number of JAK inhibitor users, short duration of exposure, and low event rate limit its precision, and there is potential misclassification of TNF/JAK inhibitor exposure, as well as confounding by indication.

Dr. Gensler noted that these same limitations apply to studies of patients with RA as well that try to answer the question of risk for MACE and malignancy when using these drugs,

“MACE is a rare event, malignancy is a rare event. So it’s like finding a needle in a haystack, and the haystack is really big. You either have to enrich the haystack with more needles or you have to make a smaller haystack,” Dr. Gensler said.

Nevertheless, she said, she credits the researchers for bringing the available information to light.

“I think we have to do this many different ways to try to get at the answer in a partial way,” she said.

The data were drawn from 2006 to 2021, but JAK inhibitors have only been approved for axSpA in the last one and a half years and for PsA at the end of 2017.

Additionally, the people taking JAK inhibitors would have likely already failed TNFis, she said, adding that this can make it hard to tell whether an event was linked with the JAK or the TNFi.
 

Nonusers may have other risk factors

She pointed out that in this study patients who were not using TNF or JAK inhibitors had slightly higher risk numerically for both MACE and VTE than did those using TNFis.

“There, the assumption is always that this is confounding by indication, meaning it is likely that the people who are nonusers have other risk factors for MACE, which is why we’re not giving them these drugs.”

Having heart failure, for instance, is a contraindication for using a TNF inhibitor, she noted. “So it’s not that these are protective compared to nonusers. It’s probably that the nonuser has higher risk and is not getting treated with these drugs to begin with.”

The authors properly concluded from the data that patients using JAK inhibitors did not have higher risk of MACE or VTE, compared with those who used TNFis, she said, but larger studies with more follow-up are needed.

“No evidence doesn’t mean no effect,” she said. “Part of it depends on the [statistical] power and the population you’re studying.”

Dr. Gensler is a consultant for AbbVie, Acceleron, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and has received grant support from Novartis and UCB. The authors’ financial relationships were not available.

Introduction

The first Janus kinase (JAK) inhibitor received regulatory approval for the treatment of psoriatic arthritis (PsA) more than 5 years ago. Although there are limited comparative data between this and other JAK inhibitors approved or in development for the treatment of PsA, it is reasonable to anticipate variability in therapeutic effect and the risk of adverse events between different JAK inhibitors. So far, there have been considerable differences in the relative selectivity of each agent on the 4 JAK isoform enzymes, JAK1, JAK2, JAK3, and TYK2. This selectivity determines the downstream signal transducers and activators of transcription proteins (JAK-STAT [signal transducer and activator of transcription] pathway) that ultimately mediate both anti-inflammatory and off-target effects. In this review of JAK inhibitors in PsA, differences between JAK inhibitors will be explored for their potential impact on benefit-to-risk ratio while treating PsA.  

Background

Data from the National Psoriasis Foundation (NPF) estimates that 8 million individuals in the United States have psoriasis.¹ PsA, an inflammatory spondyloarthritis associated with psoriasis, develops in about 30% of these individuals, but precise epidemiology on this subset of psoriasis patients is complicated by missed and delayed diagnoses. Of patients with psoriasis, only about 15% of patients with PsA have joint inflammation at the time or in advance of skin lesions.² This might explain delays in diagnosis. In one study, 15% of patients treated for psoriasis were found to have concomitant but unrecognized PsA.³ 

PsA was first classified as a distinct pathologic condition only about 50 years ago, even though skeletal remains indicate that this disease existed in early civilizations.² Based on consensus that PsA deserved definition as a distinct entity, the Classification Criteria for Psoriatic Arthritis (CASPAR) were published in 2006.⁴ By these criteria, cumulative points are allotted for clinical signs of skin, nail, and joint involvement, as well as radiographic signs in patients judged to have inflammatory disease in the joints, spine, or entheses to classify them as having PsA. 

There are numerous recommendations for the treatment of PsA, including those issued by the American College of Rheumatology (ACR),⁵ the European Alliance of Associations for Rheumatology (EULAR),⁶ and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).⁷ Although generally compatible with the others, the GRAPPA recommendations, which are the most recent, have addressed the heterogeneity of PsA by recommending therapies for specific disease domains, such as the skin, nail, and joint manifestations.

For treatment of PsA, the available drug classes for moderate-to-severe disease include immunomodulators, such as methotrexate, biologics that inhibit cytokines, such as tumor necrosis factor (TNF) and the interleukin (IL) cytokines IL-17, 1L-23, and IL12/IL-23, phosphodiesterase-4 (PDE4) inhibitors, and JAK inhibitors. In the GRAPPA recommendations, JAK inhibitors are listed along with other targeted therapies as first-line choices for peripheral arthritis, axial disease, enthesitis, dactylitis, and plaque psoriasis. 

JAK Inhibitors and PsA

There are multiple ways to classify JAK inhibitors. Tofacitinib, the first JAK inhibitor approved for PsA, is labeled a first-generation agent because it is relatively nonselective for the 4 JAK isoforms.⁸ Second-generation agents, such as upadacitinib, have been distinguished from tofacitinib, baricitinib, and other first-generation drugs by greater relative selectivity on the JAK1 enzyme. Other drugs in development for PsA target different JAK isoforms. Deucravacitinib, for example, which was approved for psoriasis after a favorable phase 3 trial⁹ and has shown promise for PsA in a phase 2 trial, is selective for the TYK2 isoform.¹⁰ A rapidly growing list of JAK inhibitors with different selectivity profiles, including dual JAK inhibitory effects, are being explored in a host of inflammatory diseases.

The relationship between selectivity on specific JAK isoforms, anti-inflammatory effects, and off-target effects is not fully understood.⁸ In addition, characteristics beyond JAK selectivity have potential pharmacologic importance. For example, JAK inhibitors can be classified as ATP competitive inhibitors and allosteric inhibitors, both of which are reversible binding modes.⁸ Within each of these subcategories, the site of kinase binding has the potential to influence clinical activity.⁸

JAK Inhibitors: Clinical Experience in PsA 

Tofacitinib, a first-generation JAK inhibitor, initially licensed for use in the treatment of rheumatoid arthritis (RA), received regulatory approval for PsA on the basis of the OPAL Beyond trial.¹¹ Approval of upadacitinib for PsA followed about 4 years later on the basis of the SELECT PsA-1 trial.¹² The primary endpoint in both of these studies was proportion of patients with an ACR response, signifying degree of improvement from baseline, of ≥20%. For the JAK inhibitors, the ACR20 rates were about 50% and 70% in the tofacitinib and upadacitinib phase 3 trials, respectively. Other JAK inhibitors have been evaluated in PsA but none so far are approved in the United States.

Despite experimental evidence supporting the hypothesis that JAK1 selectivity is clinically relevant to the treatment of PsA and other spondyloarthritides,¹³ there is no level 1 evidence of an efficacy or safety advantage for second- relative to first-generation JAK inhibitors. A small number of indirect comparisons, such as one employing a network Bayesian analysis to compare these drugs for the treatment of RA,¹⁴ have supported a clinical advantage for JAK1 selectivity, but head-to-head comparisons are needed to confirm differences. 

Prescribing information for both tofacitinib and upadacitinib in PsA and other indications include a black box warning for risk of serious adverse events, including major adverse cardiac events (MACE) and thromboembolism. The warning is based on the placebo-controlled ORAL trial with tofacitinib in RA.¹⁵ The study population was enhanced for risk with eligibility that required older age and the presence of cardiovascular risk factors. In this high-risk RA population, tofacitinib was associated with modest increases in serious adverse events, including MACE and thromboembolism, relative to placebo over several years of follow-up. A similar trial has not been conducted with upadacitinib or in patients with PsA.  

In a phase 3 trial with the TYK2-selective deucravacitinib in psoriasis, there was no increase in the rate of MACE or thromboembolism.⁹ When granted regulatory approval for psoriasis, the product information did not include a black box warning, differentiating it from other currently available JAK inhibitors. It has not yet been proven whether the absence of serious adverse events in the phase 3 psoriasis and phase 2 PsA trials with deucravacitinib are related to TYK2 JAK enzyme selectivity. 

Although TYK2 is closely associated with upregulation of IL-23 and other inflammatory cytokines implicated in the pathophysiology of PSA, the JAK-STAT signaling pathway is incompletely understood.⁸ Moreover, all of the JAK inhibitors synthesized so far have relative rather than absolute selectivity for any specific JAK isoform. This complicates the ability to attribute benefits and risks to the inhibition of any single JAK enzyme isoform and amplifies the need for comparative studies. 

While other JAK inhibitors have reached late stages of development for the treatment of PsA, such as filgotinib (a JAK1 selective drug) and brepocitinib (which is selective for both JAK1 and TYK2),^16,17 it is appropriate to emphasize that currently available JAK inhibitors are effective and acceptably safe for PsA. The goal of continued drug development is the potential to develop agents with even greater efficacy but with a lower risk of off-target effects. Currently, the black box warnings included in the labeling of tofacitinib and upadacitinib give pause, leading many clinicians to move to these agents after an inadequate response to biologics. Newer therapies in the JAK inhibitor class free of serious adverse effects might reverse the order, given the preference of many patients for oral agents. 

The JAK inhibitor development program is rich not just for inflammatory diseases and autoimmune diseases, but for myeloproliferative diseases and neoplasms. JAK inhibitors are already identified in the GRAPPA recommendations as appropriate first-line options for most manifestations of PsA, including joint and skin involvement, but newer drugs with a more favorable JAK selectivity or other pharmacologic characteristics and decreased adverse risks might make these a more dominant treatment choice. 

Summary

Relative selectivity for JAK isoforms promises therapies that are both more effective and safer for PsA as well as other inflammatory diseases. This promise is now being explored in experimental trials testing therapies with variable degrees of selectivity in the context of other characteristics, such as kinase binding, with the potential to influence clinical effects. However, the promise will not be fulfilled until large clinical trials, particularly comparative trials, can confirm the importance of JAK isoform selectivity. If specific types of selectivity prove relevant to the benefit-to-risk ratio of JAK inhibitors in PsA, it may alter the current order of treatment preferences for this disease.

Introduction

The first Janus kinase (JAK) inhibitor received regulatory approval for the treatment of psoriatic arthritis (PsA) more than 5 years ago. Although there are limited comparative data between this and other JAK inhibitors approved or in development for the treatment of PsA, it is reasonable to anticipate variability in therapeutic effect and the risk of adverse events between different JAK inhibitors. So far, there have been considerable differences in the relative selectivity of each agent on the 4 JAK isoform enzymes, JAK1, JAK2, JAK3, and TYK2. This selectivity determines the downstream signal transducers and activators of transcription proteins (JAK-STAT [signal transducer and activator of transcription] pathway) that ultimately mediate both anti-inflammatory and off-target effects. In this review of JAK inhibitors in PsA, differences between JAK inhibitors will be explored for their potential impact on benefit-to-risk ratio while treating PsA.  

Background

Data from the National Psoriasis Foundation (NPF) estimates that 8 million individuals in the United States have psoriasis.¹ PsA, an inflammatory spondyloarthritis associated with psoriasis, develops in about 30% of these individuals, but precise epidemiology on this subset of psoriasis patients is complicated by missed and delayed diagnoses. Of patients with psoriasis, only about 15% of patients with PsA have joint inflammation at the time or in advance of skin lesions.² This might explain delays in diagnosis. In one study, 15% of patients treated for psoriasis were found to have concomitant but unrecognized PsA.³ 

PsA was first classified as a distinct pathologic condition only about 50 years ago, even though skeletal remains indicate that this disease existed in early civilizations.² Based on consensus that PsA deserved definition as a distinct entity, the Classification Criteria for Psoriatic Arthritis (CASPAR) were published in 2006.⁴ By these criteria, cumulative points are allotted for clinical signs of skin, nail, and joint involvement, as well as radiographic signs in patients judged to have inflammatory disease in the joints, spine, or entheses to classify them as having PsA. 

There are numerous recommendations for the treatment of PsA, including those issued by the American College of Rheumatology (ACR),⁵ the European Alliance of Associations for Rheumatology (EULAR),⁶ and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).⁷ Although generally compatible with the others, the GRAPPA recommendations, which are the most recent, have addressed the heterogeneity of PsA by recommending therapies for specific disease domains, such as the skin, nail, and joint manifestations.

For treatment of PsA, the available drug classes for moderate-to-severe disease include immunomodulators, such as methotrexate, biologics that inhibit cytokines, such as tumor necrosis factor (TNF) and the interleukin (IL) cytokines IL-17, 1L-23, and IL12/IL-23, phosphodiesterase-4 (PDE4) inhibitors, and JAK inhibitors. In the GRAPPA recommendations, JAK inhibitors are listed along with other targeted therapies as first-line choices for peripheral arthritis, axial disease, enthesitis, dactylitis, and plaque psoriasis. 

JAK Inhibitors and PsA

There are multiple ways to classify JAK inhibitors. Tofacitinib, the first JAK inhibitor approved for PsA, is labeled a first-generation agent because it is relatively nonselective for the 4 JAK isoforms.⁸ Second-generation agents, such as upadacitinib, have been distinguished from tofacitinib, baricitinib, and other first-generation drugs by greater relative selectivity on the JAK1 enzyme. Other drugs in development for PsA target different JAK isoforms. Deucravacitinib, for example, which was approved for psoriasis after a favorable phase 3 trial⁹ and has shown promise for PsA in a phase 2 trial, is selective for the TYK2 isoform.¹⁰ A rapidly growing list of JAK inhibitors with different selectivity profiles, including dual JAK inhibitory effects, are being explored in a host of inflammatory diseases.

The relationship between selectivity on specific JAK isoforms, anti-inflammatory effects, and off-target effects is not fully understood.⁸ In addition, characteristics beyond JAK selectivity have potential pharmacologic importance. For example, JAK inhibitors can be classified as ATP competitive inhibitors and allosteric inhibitors, both of which are reversible binding modes.⁸ Within each of these subcategories, the site of kinase binding has the potential to influence clinical activity.⁸

JAK Inhibitors: Clinical Experience in PsA 

Tofacitinib, a first-generation JAK inhibitor, initially licensed for use in the treatment of rheumatoid arthritis (RA), received regulatory approval for PsA on the basis of the OPAL Beyond trial.¹¹ Approval of upadacitinib for PsA followed about 4 years later on the basis of the SELECT PsA-1 trial.¹² The primary endpoint in both of these studies was proportion of patients with an ACR response, signifying degree of improvement from baseline, of ≥20%. For the JAK inhibitors, the ACR20 rates were about 50% and 70% in the tofacitinib and upadacitinib phase 3 trials, respectively. Other JAK inhibitors have been evaluated in PsA but none so far are approved in the United States.

Despite experimental evidence supporting the hypothesis that JAK1 selectivity is clinically relevant to the treatment of PsA and other spondyloarthritides,¹³ there is no level 1 evidence of an efficacy or safety advantage for second- relative to first-generation JAK inhibitors. A small number of indirect comparisons, such as one employing a network Bayesian analysis to compare these drugs for the treatment of RA,¹⁴ have supported a clinical advantage for JAK1 selectivity, but head-to-head comparisons are needed to confirm differences. 

Prescribing information for both tofacitinib and upadacitinib in PsA and other indications include a black box warning for risk of serious adverse events, including major adverse cardiac events (MACE) and thromboembolism. The warning is based on the placebo-controlled ORAL trial with tofacitinib in RA.¹⁵ The study population was enhanced for risk with eligibility that required older age and the presence of cardiovascular risk factors. In this high-risk RA population, tofacitinib was associated with modest increases in serious adverse events, including MACE and thromboembolism, relative to placebo over several years of follow-up. A similar trial has not been conducted with upadacitinib or in patients with PsA.  

In a phase 3 trial with the TYK2-selective deucravacitinib in psoriasis, there was no increase in the rate of MACE or thromboembolism.⁹ When granted regulatory approval for psoriasis, the product information did not include a black box warning, differentiating it from other currently available JAK inhibitors. It has not yet been proven whether the absence of serious adverse events in the phase 3 psoriasis and phase 2 PsA trials with deucravacitinib are related to TYK2 JAK enzyme selectivity. 

Although TYK2 is closely associated with upregulation of IL-23 and other inflammatory cytokines implicated in the pathophysiology of PSA, the JAK-STAT signaling pathway is incompletely understood.⁸ Moreover, all of the JAK inhibitors synthesized so far have relative rather than absolute selectivity for any specific JAK isoform. This complicates the ability to attribute benefits and risks to the inhibition of any single JAK enzyme isoform and amplifies the need for comparative studies. 

While other JAK inhibitors have reached late stages of development for the treatment of PsA, such as filgotinib (a JAK1 selective drug) and brepocitinib (which is selective for both JAK1 and TYK2),^16,17 it is appropriate to emphasize that currently available JAK inhibitors are effective and acceptably safe for PsA. The goal of continued drug development is the potential to develop agents with even greater efficacy but with a lower risk of off-target effects. Currently, the black box warnings included in the labeling of tofacitinib and upadacitinib give pause, leading many clinicians to move to these agents after an inadequate response to biologics. Newer therapies in the JAK inhibitor class free of serious adverse effects might reverse the order, given the preference of many patients for oral agents. 

The JAK inhibitor development program is rich not just for inflammatory diseases and autoimmune diseases, but for myeloproliferative diseases and neoplasms. JAK inhibitors are already identified in the GRAPPA recommendations as appropriate first-line options for most manifestations of PsA, including joint and skin involvement, but newer drugs with a more favorable JAK selectivity or other pharmacologic characteristics and decreased adverse risks might make these a more dominant treatment choice. 

Summary

Relative selectivity for JAK isoforms promises therapies that are both more effective and safer for PsA as well as other inflammatory diseases. This promise is now being explored in experimental trials testing therapies with variable degrees of selectivity in the context of other characteristics, such as kinase binding, with the potential to influence clinical effects. However, the promise will not be fulfilled until large clinical trials, particularly comparative trials, can confirm the importance of JAK isoform selectivity. If specific types of selectivity prove relevant to the benefit-to-risk ratio of JAK inhibitors in PsA, it may alter the current order of treatment preferences for this disease.

Introduction

The first Janus kinase (JAK) inhibitor received regulatory approval for the treatment of psoriatic arthritis (PsA) more than 5 years ago. Although there are limited comparative data between this and other JAK inhibitors approved or in development for the treatment of PsA, it is reasonable to anticipate variability in therapeutic effect and the risk of adverse events between different JAK inhibitors. So far, there have been considerable differences in the relative selectivity of each agent on the 4 JAK isoform enzymes, JAK1, JAK2, JAK3, and TYK2. This selectivity determines the downstream signal transducers and activators of transcription proteins (JAK-STAT [signal transducer and activator of transcription] pathway) that ultimately mediate both anti-inflammatory and off-target effects. In this review of JAK inhibitors in PsA, differences between JAK inhibitors will be explored for their potential impact on benefit-to-risk ratio while treating PsA.  

Background

Data from the National Psoriasis Foundation (NPF) estimates that 8 million individuals in the United States have psoriasis.¹ PsA, an inflammatory spondyloarthritis associated with psoriasis, develops in about 30% of these individuals, but precise epidemiology on this subset of psoriasis patients is complicated by missed and delayed diagnoses. Of patients with psoriasis, only about 15% of patients with PsA have joint inflammation at the time or in advance of skin lesions.² This might explain delays in diagnosis. In one study, 15% of patients treated for psoriasis were found to have concomitant but unrecognized PsA.³ 

PsA was first classified as a distinct pathologic condition only about 50 years ago, even though skeletal remains indicate that this disease existed in early civilizations.² Based on consensus that PsA deserved definition as a distinct entity, the Classification Criteria for Psoriatic Arthritis (CASPAR) were published in 2006.⁴ By these criteria, cumulative points are allotted for clinical signs of skin, nail, and joint involvement, as well as radiographic signs in patients judged to have inflammatory disease in the joints, spine, or entheses to classify them as having PsA. 

There are numerous recommendations for the treatment of PsA, including those issued by the American College of Rheumatology (ACR),⁵ the European Alliance of Associations for Rheumatology (EULAR),⁶ and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).⁷ Although generally compatible with the others, the GRAPPA recommendations, which are the most recent, have addressed the heterogeneity of PsA by recommending therapies for specific disease domains, such as the skin, nail, and joint manifestations.

For treatment of PsA, the available drug classes for moderate-to-severe disease include immunomodulators, such as methotrexate, biologics that inhibit cytokines, such as tumor necrosis factor (TNF) and the interleukin (IL) cytokines IL-17, 1L-23, and IL12/IL-23, phosphodiesterase-4 (PDE4) inhibitors, and JAK inhibitors. In the GRAPPA recommendations, JAK inhibitors are listed along with other targeted therapies as first-line choices for peripheral arthritis, axial disease, enthesitis, dactylitis, and plaque psoriasis. 

JAK Inhibitors and PsA

There are multiple ways to classify JAK inhibitors. Tofacitinib, the first JAK inhibitor approved for PsA, is labeled a first-generation agent because it is relatively nonselective for the 4 JAK isoforms.⁸ Second-generation agents, such as upadacitinib, have been distinguished from tofacitinib, baricitinib, and other first-generation drugs by greater relative selectivity on the JAK1 enzyme. Other drugs in development for PsA target different JAK isoforms. Deucravacitinib, for example, which was approved for psoriasis after a favorable phase 3 trial⁹ and has shown promise for PsA in a phase 2 trial, is selective for the TYK2 isoform.¹⁰ A rapidly growing list of JAK inhibitors with different selectivity profiles, including dual JAK inhibitory effects, are being explored in a host of inflammatory diseases.

The relationship between selectivity on specific JAK isoforms, anti-inflammatory effects, and off-target effects is not fully understood.⁸ In addition, characteristics beyond JAK selectivity have potential pharmacologic importance. For example, JAK inhibitors can be classified as ATP competitive inhibitors and allosteric inhibitors, both of which are reversible binding modes.⁸ Within each of these subcategories, the site of kinase binding has the potential to influence clinical activity.⁸

JAK Inhibitors: Clinical Experience in PsA 

Tofacitinib, a first-generation JAK inhibitor, initially licensed for use in the treatment of rheumatoid arthritis (RA), received regulatory approval for PsA on the basis of the OPAL Beyond trial.¹¹ Approval of upadacitinib for PsA followed about 4 years later on the basis of the SELECT PsA-1 trial.¹² The primary endpoint in both of these studies was proportion of patients with an ACR response, signifying degree of improvement from baseline, of ≥20%. For the JAK inhibitors, the ACR20 rates were about 50% and 70% in the tofacitinib and upadacitinib phase 3 trials, respectively. Other JAK inhibitors have been evaluated in PsA but none so far are approved in the United States.

Despite experimental evidence supporting the hypothesis that JAK1 selectivity is clinically relevant to the treatment of PsA and other spondyloarthritides,¹³ there is no level 1 evidence of an efficacy or safety advantage for second- relative to first-generation JAK inhibitors. A small number of indirect comparisons, such as one employing a network Bayesian analysis to compare these drugs for the treatment of RA,¹⁴ have supported a clinical advantage for JAK1 selectivity, but head-to-head comparisons are needed to confirm differences. 

Prescribing information for both tofacitinib and upadacitinib in PsA and other indications include a black box warning for risk of serious adverse events, including major adverse cardiac events (MACE) and thromboembolism. The warning is based on the placebo-controlled ORAL trial with tofacitinib in RA.¹⁵ The study population was enhanced for risk with eligibility that required older age and the presence of cardiovascular risk factors. In this high-risk RA population, tofacitinib was associated with modest increases in serious adverse events, including MACE and thromboembolism, relative to placebo over several years of follow-up. A similar trial has not been conducted with upadacitinib or in patients with PsA.  

In a phase 3 trial with the TYK2-selective deucravacitinib in psoriasis, there was no increase in the rate of MACE or thromboembolism.⁹ When granted regulatory approval for psoriasis, the product information did not include a black box warning, differentiating it from other currently available JAK inhibitors. It has not yet been proven whether the absence of serious adverse events in the phase 3 psoriasis and phase 2 PsA trials with deucravacitinib are related to TYK2 JAK enzyme selectivity. 

Although TYK2 is closely associated with upregulation of IL-23 and other inflammatory cytokines implicated in the pathophysiology of PSA, the JAK-STAT signaling pathway is incompletely understood.⁸ Moreover, all of the JAK inhibitors synthesized so far have relative rather than absolute selectivity for any specific JAK isoform. This complicates the ability to attribute benefits and risks to the inhibition of any single JAK enzyme isoform and amplifies the need for comparative studies. 

While other JAK inhibitors have reached late stages of development for the treatment of PsA, such as filgotinib (a JAK1 selective drug) and brepocitinib (which is selective for both JAK1 and TYK2),^16,17 it is appropriate to emphasize that currently available JAK inhibitors are effective and acceptably safe for PsA. The goal of continued drug development is the potential to develop agents with even greater efficacy but with a lower risk of off-target effects. Currently, the black box warnings included in the labeling of tofacitinib and upadacitinib give pause, leading many clinicians to move to these agents after an inadequate response to biologics. Newer therapies in the JAK inhibitor class free of serious adverse effects might reverse the order, given the preference of many patients for oral agents. 

The JAK inhibitor development program is rich not just for inflammatory diseases and autoimmune diseases, but for myeloproliferative diseases and neoplasms. JAK inhibitors are already identified in the GRAPPA recommendations as appropriate first-line options for most manifestations of PsA, including joint and skin involvement, but newer drugs with a more favorable JAK selectivity or other pharmacologic characteristics and decreased adverse risks might make these a more dominant treatment choice. 

Summary

Relative selectivity for JAK isoforms promises therapies that are both more effective and safer for PsA as well as other inflammatory diseases. This promise is now being explored in experimental trials testing therapies with variable degrees of selectivity in the context of other characteristics, such as kinase binding, with the potential to influence clinical effects. However, the promise will not be fulfilled until large clinical trials, particularly comparative trials, can confirm the importance of JAK isoform selectivity. If specific types of selectivity prove relevant to the benefit-to-risk ratio of JAK inhibitors in PsA, it may alter the current order of treatment preferences for this disease.

Key clinical point: A referral tool based on five independent risk factors for concomitant psoriatic arthritis (PsA) among patients with psoriasis may help dermatologists to identify patients with psoriasis who could benefit from a rheumatologist referral.

Major finding: The predictive variables for concomitant PsA among patients with psoriasis that were included in the referral tool were treatment history with conventional systemics (P  =  .04) and biologics/small molecule inhibitors (P  =  .01), patient-reported history of joint pain without trauma (P  =  .02), swollen joints (P < .001), and sausage-like swollen digits (P  =  .01). The referral tool had an area under curve of 0.82.

Study details: This study analyzed the data of 303 patients with psoriasis from the prospective observational DAPPER study who had visited the dermatology outpatient clinic.

Disclosures: This study was funded by a PhD grant from Radboud University Medical Center/Sint Maartenskliniek, Netherlands, and local structural research funding of the Sint Maartenskliniek. Several authors reported financial and non-financial ties with various sources.

Source: van Hal TW et al. Development of a new referral tool to identify psoriasis patients with concomitant psoriatic arthritis: Results of the prospective DAPPER cohort. Acta Derm Venereol. 2023 (Apr 27). Doi: 10.2340/actadv.v103.5269

Key clinical point: A referral tool based on five independent risk factors for concomitant psoriatic arthritis (PsA) among patients with psoriasis may help dermatologists to identify patients with psoriasis who could benefit from a rheumatologist referral.

Major finding: The predictive variables for concomitant PsA among patients with psoriasis that were included in the referral tool were treatment history with conventional systemics (P  =  .04) and biologics/small molecule inhibitors (P  =  .01), patient-reported history of joint pain without trauma (P  =  .02), swollen joints (P < .001), and sausage-like swollen digits (P  =  .01). The referral tool had an area under curve of 0.82.

Study details: This study analyzed the data of 303 patients with psoriasis from the prospective observational DAPPER study who had visited the dermatology outpatient clinic.

Disclosures: This study was funded by a PhD grant from Radboud University Medical Center/Sint Maartenskliniek, Netherlands, and local structural research funding of the Sint Maartenskliniek. Several authors reported financial and non-financial ties with various sources.

Source: van Hal TW et al. Development of a new referral tool to identify psoriasis patients with concomitant psoriatic arthritis: Results of the prospective DAPPER cohort. Acta Derm Venereol. 2023 (Apr 27). Doi: 10.2340/actadv.v103.5269

Key clinical point: A referral tool based on five independent risk factors for concomitant psoriatic arthritis (PsA) among patients with psoriasis may help dermatologists to identify patients with psoriasis who could benefit from a rheumatologist referral.

Major finding: The predictive variables for concomitant PsA among patients with psoriasis that were included in the referral tool were treatment history with conventional systemics (P  =  .04) and biologics/small molecule inhibitors (P  =  .01), patient-reported history of joint pain without trauma (P  =  .02), swollen joints (P < .001), and sausage-like swollen digits (P  =  .01). The referral tool had an area under curve of 0.82.

Study details: This study analyzed the data of 303 patients with psoriasis from the prospective observational DAPPER study who had visited the dermatology outpatient clinic.

Disclosures: This study was funded by a PhD grant from Radboud University Medical Center/Sint Maartenskliniek, Netherlands, and local structural research funding of the Sint Maartenskliniek. Several authors reported financial and non-financial ties with various sources.

Source: van Hal TW et al. Development of a new referral tool to identify psoriasis patients with concomitant psoriatic arthritis: Results of the prospective DAPPER cohort. Acta Derm Venereol. 2023 (Apr 27). Doi: 10.2340/actadv.v103.5269

Key clinical point: The occurrence of radiographic spinal damage was overall low among patients with psoriatic arthritis (PsA) and spondyloarthritis; however, severe spinal damage and the extent of syndesmophytes led spinal damage were more observed in spondyloarthritis vs PsA.

Major finding: Proportion of patients with PsA vs spondyloarthritis experiencing spinal damage was comparable (10.6% vs 7.9%; P  =  .320). However, patients with spondyloarthritis and spinal damage vs PsA had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating severe spinal damage (P < .05). Syndesmophytes were significantly higher in the total spine of patients with spondyloarthritis vs PsA (P < .05).

Study details: This study evaluated patients with PsA (n = 312) and spondyloarthritis (n = 213) who had undergone radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and observational Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively.

Disclosures: The BEPAS and Be-GIANT studies were funded by Merck Sharp Dohme Belgium and AbbVie, respectively. Several authors reported ties with various companies, including AbbVie or Merck Sharp Dohme.

Source: de Hooge M et al. Extent of axial damage in psoriatic arthritis and spondyloarthritis: Comparative data from the BEPAS and (Be-)GIANT multicentre cohorts. RMD Open. 2023;9(2):e002994 (May 3). Doi: 10.1136/rmdopen-2023-002994

Key clinical point: The occurrence of radiographic spinal damage was overall low among patients with psoriatic arthritis (PsA) and spondyloarthritis; however, severe spinal damage and the extent of syndesmophytes led spinal damage were more observed in spondyloarthritis vs PsA.

Major finding: Proportion of patients with PsA vs spondyloarthritis experiencing spinal damage was comparable (10.6% vs 7.9%; P  =  .320). However, patients with spondyloarthritis and spinal damage vs PsA had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating severe spinal damage (P < .05). Syndesmophytes were significantly higher in the total spine of patients with spondyloarthritis vs PsA (P < .05).

Study details: This study evaluated patients with PsA (n = 312) and spondyloarthritis (n = 213) who had undergone radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and observational Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively.

Disclosures: The BEPAS and Be-GIANT studies were funded by Merck Sharp Dohme Belgium and AbbVie, respectively. Several authors reported ties with various companies, including AbbVie or Merck Sharp Dohme.

Source: de Hooge M et al. Extent of axial damage in psoriatic arthritis and spondyloarthritis: Comparative data from the BEPAS and (Be-)GIANT multicentre cohorts. RMD Open. 2023;9(2):e002994 (May 3). Doi: 10.1136/rmdopen-2023-002994

Key clinical point: The occurrence of radiographic spinal damage was overall low among patients with psoriatic arthritis (PsA) and spondyloarthritis; however, severe spinal damage and the extent of syndesmophytes led spinal damage were more observed in spondyloarthritis vs PsA.

Major finding: Proportion of patients with PsA vs spondyloarthritis experiencing spinal damage was comparable (10.6% vs 7.9%; P  =  .320). However, patients with spondyloarthritis and spinal damage vs PsA had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating severe spinal damage (P < .05). Syndesmophytes were significantly higher in the total spine of patients with spondyloarthritis vs PsA (P < .05).

Study details: This study evaluated patients with PsA (n = 312) and spondyloarthritis (n = 213) who had undergone radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and observational Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively.

Disclosures: The BEPAS and Be-GIANT studies were funded by Merck Sharp Dohme Belgium and AbbVie, respectively. Several authors reported ties with various companies, including AbbVie or Merck Sharp Dohme.

Source: de Hooge M et al. Extent of axial damage in psoriatic arthritis and spondyloarthritis: Comparative data from the BEPAS and (Be-)GIANT multicentre cohorts. RMD Open. 2023;9(2):e002994 (May 3). Doi: 10.1136/rmdopen-2023-002994

Key clinical point: Secukinumab reduced disease activity at week 12, which sustained or improved by week 52, and demonstrated a consistent safety profile in patients with oligoarticular psoriatic arthritis (PsA).

Major finding: At week 12, 50% improvement in Disease Activity Index for Psoriatic Arthritis (DAPSA50) was achieved by a higher proportion of patients treated with 300 mg or 150 mg secukinumab vs placebo-treated patients (65.2% and 44.4% vs 30.0%, respectively). DAPSA50 responses further improved with 300 mg and 150 mg secukinumab at week 52 (74.2% and 71.8%; respectively). The safety profile of secukinumab was consistent with that reported in the original trials.

Study details: This post hoc analysis of the phase 3/3b FUTURE 2-5 and MAXIMISE trials included 84 patients with oligoarticular PsA who were randomly assigned to receive 150 or 300 mg secukinumab or placebo until week 12 and 150 or 300 mg `secukinumab from week 12 to 52.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. Some authors declared being employees and holding stocks or shares or having other ties with Novartis or others.

Source: Ogdie A et al. Inhibition of interleukin-17 in patients with oligoarticular psoriatic arthritis. Rheumatol Ther. 2023 (May 6). Doi: 10.1007/s40744-023-00548-y

Key clinical point: Secukinumab reduced disease activity at week 12, which sustained or improved by week 52, and demonstrated a consistent safety profile in patients with oligoarticular psoriatic arthritis (PsA).

Major finding: At week 12, 50% improvement in Disease Activity Index for Psoriatic Arthritis (DAPSA50) was achieved by a higher proportion of patients treated with 300 mg or 150 mg secukinumab vs placebo-treated patients (65.2% and 44.4% vs 30.0%, respectively). DAPSA50 responses further improved with 300 mg and 150 mg secukinumab at week 52 (74.2% and 71.8%; respectively). The safety profile of secukinumab was consistent with that reported in the original trials.

Study details: This post hoc analysis of the phase 3/3b FUTURE 2-5 and MAXIMISE trials included 84 patients with oligoarticular PsA who were randomly assigned to receive 150 or 300 mg secukinumab or placebo until week 12 and 150 or 300 mg `secukinumab from week 12 to 52.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. Some authors declared being employees and holding stocks or shares or having other ties with Novartis or others.

Source: Ogdie A et al. Inhibition of interleukin-17 in patients with oligoarticular psoriatic arthritis. Rheumatol Ther. 2023 (May 6). Doi: 10.1007/s40744-023-00548-y

Key clinical point: Secukinumab reduced disease activity at week 12, which sustained or improved by week 52, and demonstrated a consistent safety profile in patients with oligoarticular psoriatic arthritis (PsA).

Major finding: At week 12, 50% improvement in Disease Activity Index for Psoriatic Arthritis (DAPSA50) was achieved by a higher proportion of patients treated with 300 mg or 150 mg secukinumab vs placebo-treated patients (65.2% and 44.4% vs 30.0%, respectively). DAPSA50 responses further improved with 300 mg and 150 mg secukinumab at week 52 (74.2% and 71.8%; respectively). The safety profile of secukinumab was consistent with that reported in the original trials.

Study details: This post hoc analysis of the phase 3/3b FUTURE 2-5 and MAXIMISE trials included 84 patients with oligoarticular PsA who were randomly assigned to receive 150 or 300 mg secukinumab or placebo until week 12 and 150 or 300 mg `secukinumab from week 12 to 52.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation. Some authors declared being employees and holding stocks or shares or having other ties with Novartis or others.

Source: Ogdie A et al. Inhibition of interleukin-17 in patients with oligoarticular psoriatic arthritis. Rheumatol Ther. 2023 (May 6). Doi: 10.1007/s40744-023-00548-y

Key clinical point: Patients with higher platelet lymphocyte ratio (PLR) or C-reactive protein (CRP) levels were more likely to be diagnosed with psoriatic arthritis (PsA) than psoriasis vulgaris (PsV), with patients having higher pretreatment systemic inflammatory marker scores showing lower treatment persistence with conventional therapies.

Major finding: PLR (odds ratio [OR] 7.027; P  =  .040) or CRP levels (OR 3.179; P  =  .022) at the time of initial presentation were associated with a higher probability of PsA vs PsV diagnosis, with patients having higher pretreatment platelet or neutrophil counts, PLR, and systemic immune/inflammation index scores exhibiting lower treatment continuation rates for conventional systemic agents (all P < .05).

Study details: Findings are from a retrospective analysis including patients with PsA (n = 47) and PsV (n = 117) and control individuals with no history of allergy or skin diseases (n = 50).

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Sugimoto E, Matsuda H, et al. Impact of pretreatment systemic inflammatory markers on treatment persistence with biologics and conventional systemic therapy: A retrospective study of patients with psoriasis vulgaris and psoriatic arthritis. J Clin Med. 2023;12(8):3046 (Apr 21). Doi: 10.3390/jcm12083046

Key clinical point: Patients with higher platelet lymphocyte ratio (PLR) or C-reactive protein (CRP) levels were more likely to be diagnosed with psoriatic arthritis (PsA) than psoriasis vulgaris (PsV), with patients having higher pretreatment systemic inflammatory marker scores showing lower treatment persistence with conventional therapies.

Major finding: PLR (odds ratio [OR] 7.027; P  =  .040) or CRP levels (OR 3.179; P  =  .022) at the time of initial presentation were associated with a higher probability of PsA vs PsV diagnosis, with patients having higher pretreatment platelet or neutrophil counts, PLR, and systemic immune/inflammation index scores exhibiting lower treatment continuation rates for conventional systemic agents (all P < .05).

Study details: Findings are from a retrospective analysis including patients with PsA (n = 47) and PsV (n = 117) and control individuals with no history of allergy or skin diseases (n = 50).

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Sugimoto E, Matsuda H, et al. Impact of pretreatment systemic inflammatory markers on treatment persistence with biologics and conventional systemic therapy: A retrospective study of patients with psoriasis vulgaris and psoriatic arthritis. J Clin Med. 2023;12(8):3046 (Apr 21). Doi: 10.3390/jcm12083046

Key clinical point: Patients with higher platelet lymphocyte ratio (PLR) or C-reactive protein (CRP) levels were more likely to be diagnosed with psoriatic arthritis (PsA) than psoriasis vulgaris (PsV), with patients having higher pretreatment systemic inflammatory marker scores showing lower treatment persistence with conventional therapies.

Major finding: PLR (odds ratio [OR] 7.027; P  =  .040) or CRP levels (OR 3.179; P  =  .022) at the time of initial presentation were associated with a higher probability of PsA vs PsV diagnosis, with patients having higher pretreatment platelet or neutrophil counts, PLR, and systemic immune/inflammation index scores exhibiting lower treatment continuation rates for conventional systemic agents (all P < .05).

Study details: Findings are from a retrospective analysis including patients with PsA (n = 47) and PsV (n = 117) and control individuals with no history of allergy or skin diseases (n = 50).

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Sugimoto E, Matsuda H, et al. Impact of pretreatment systemic inflammatory markers on treatment persistence with biologics and conventional systemic therapy: A retrospective study of patients with psoriasis vulgaris and psoriatic arthritis. J Clin Med. 2023;12(8):3046 (Apr 21). Doi: 10.3390/jcm12083046

Key clinical point: Concomitant methotrexate had no effect on ustekimumab immunogenicity in patients with psoriatic arthritis (PsA), with the formation of antidrug antibody (ADA) not being associated with reductions in ustekinumab safety or efficacy.

Major finding: The prevalence of ADA at week 52 was not significantly different between the ustekinumab+methotrexate and ustekinumab+placebo groups, with disease activity, treatment response, dropout rates, effect of pretreatment with methotrexate, and safety outcomes not being significantly different in patients with vs without ADA (all P > .05).

Study details: This post hoc analysis of the MUST trial included 112 patients with active PsA who were naive to ustekimumab and were randomly assigned to receive ustekinumab with concomitant methotrexate or placebo.

Disclosures: This study was funded by Innovative Medicines Initiative 2 Joint Undertaking, which received support from the European Union’s Horizon 2020 Research and Innovation Program and others. F Behrens, M Koehm, and H Burkhardt declared receiving research grants from Janssen Cilag. The other authors reported no conflicts of interest.

Source: Poor SM et al. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 (Apr 20). Doi: 10.1093/rheumatology/kead177

Key clinical point: Concomitant methotrexate had no effect on ustekimumab immunogenicity in patients with psoriatic arthritis (PsA), with the formation of antidrug antibody (ADA) not being associated with reductions in ustekinumab safety or efficacy.

Major finding: The prevalence of ADA at week 52 was not significantly different between the ustekinumab+methotrexate and ustekinumab+placebo groups, with disease activity, treatment response, dropout rates, effect of pretreatment with methotrexate, and safety outcomes not being significantly different in patients with vs without ADA (all P > .05).

Study details: This post hoc analysis of the MUST trial included 112 patients with active PsA who were naive to ustekimumab and were randomly assigned to receive ustekinumab with concomitant methotrexate or placebo.

Disclosures: This study was funded by Innovative Medicines Initiative 2 Joint Undertaking, which received support from the European Union’s Horizon 2020 Research and Innovation Program and others. F Behrens, M Koehm, and H Burkhardt declared receiving research grants from Janssen Cilag. The other authors reported no conflicts of interest.

Source: Poor SM et al. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 (Apr 20). Doi: 10.1093/rheumatology/kead177

Key clinical point: Concomitant methotrexate had no effect on ustekimumab immunogenicity in patients with psoriatic arthritis (PsA), with the formation of antidrug antibody (ADA) not being associated with reductions in ustekinumab safety or efficacy.

Major finding: The prevalence of ADA at week 52 was not significantly different between the ustekinumab+methotrexate and ustekinumab+placebo groups, with disease activity, treatment response, dropout rates, effect of pretreatment with methotrexate, and safety outcomes not being significantly different in patients with vs without ADA (all P > .05).

Study details: This post hoc analysis of the MUST trial included 112 patients with active PsA who were naive to ustekimumab and were randomly assigned to receive ustekinumab with concomitant methotrexate or placebo.

Disclosures: This study was funded by Innovative Medicines Initiative 2 Joint Undertaking, which received support from the European Union’s Horizon 2020 Research and Innovation Program and others. F Behrens, M Koehm, and H Burkhardt declared receiving research grants from Janssen Cilag. The other authors reported no conflicts of interest.

Source: Poor SM et al. The role of antidrug antibodies in ustekinumab therapy and the impact of methotrexate. Rheumatology (Oxford). 2023 (Apr 20). Doi: 10.1093/rheumatology/kead177