Psoriatic Arthritis Resource Center

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

Michielsens_Celia_NETH_web.jpg

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

[embed:render:related:node:225445]

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

[embed:render:related:node:223732]

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

Michielsens_Celia_NETH_web.jpg

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

[embed:render:related:node:225445]

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

[embed:render:related:node:223732]

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.

The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.

Michielsens_Celia_NETH_web.jpg

“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”

The study is now published in Annals of the Rheumatic Diseases.

[embed:render:related:node:225445]

In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).

Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”

Results show strategy is ‘feasible in daily clinical care’

A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.

At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.

The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).

The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).

Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.

Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.

[embed:render:related:node:223732]

“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”

The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.

“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.

The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.

“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”

This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

158538_Merola_Joseph_web.JPG

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

158538_McInnes_Iain_web.JPG

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

[embed:render:related:node:244644]

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

[embed:render:related:node:238207]

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

158538_Merola_Joseph_web.JPG

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

158538_McInnes_Iain_web.JPG

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

[embed:render:related:node:244644]

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

[embed:render:related:node:238207]

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

COPENHAGEN – For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.

The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women’s Hospital in Boston.

158538_Merola_Joseph_web.JPG

“The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16,” he said at the annual European Congress of Rheumatology.

Also at the congress, Iain McInnes, MD, PhD, of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.

158538_McInnes_Iain_web.JPG

“This is a new mode of action, inhibiting two cytokines simultaneously,” he said in a late-breaking oral abstract session.

As previously reported by this news organization, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.

Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
 

BE COMPLETE efficacy

Inclusion criteria comprised adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of at least 3/68; one or more active psoriatic lesions; and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.

Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.

[embed:render:related:node:244644]

As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).

In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36-Item Health Survey, and minimal disease activity (P < .001 for all comparisons).

Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Dr. Merola said.

BE OPTIMAL efficacy

In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.

This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).

In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
 

Safety

More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.

[embed:render:related:node:238207]

The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.

Patients tolerated bimekizumab well, and there were no unexpected safety signals, Dr. McInnes said.
 

Clues to efficacy

In the question-and-answer session following Dr. McInnes’ presentation, Ronald Van Vollenhoven, MD, of the University of Amsterdam, said, “I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent – PASI90 sounds wonderful – but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?”

Dr. McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, “it doesn’t seem to be a major determinant of the outcome.”

The studies were supported by UCB Pharma. Dr. Merola and Dr. McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Dr. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.

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

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

[embed:render:related:node:241230]

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

[embed:render:related:node:241230]

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

[embed:render:related:node:241230]

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

FDA_icon3_web.jpg

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

[embed:render:related:node:247373]

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

[embed:render:related:node:213422]

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

FDA_icon3_web.jpg

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

[embed:render:related:node:247373]

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

[embed:render:related:node:213422]

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

FDA_icon3_web.jpg

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

[embed:render:related:node:247373]

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

[embed:render:related:node:213422]

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

For patients with psoriatic arthritis (PsA) whose condition doesn’t respond adequately to methotrexate, addition of the tumor necrosis factor (TNF) inhibitor adalimumab increased the likelihood of achieving minimum disease activity (MDA), compared with escalation of MTX dose, according to results from a phase 4, open-label study.

The new study is one of only a few to compare treatment protocols in a field that has seen new therapeutic options become available in recent years. That lack of evidence can leave patients and physicians uncertain about the next step if the initial results of treatment are disappointing.

Kavanaugh_Arthur_CA_1_web.jpg

“There are some gaps in our database and our understanding of psoriatic arthritis, compared to rheumatoid arthritis, where we have had many more studies over the years,” Arthur Kavanaugh, MD, told this news organization when asked to comment on the study.

The trial provides one answer, at least. “There was a clear-cut signal that it made more sense to add adalimumab at that early juncture where a person is not quite doing well enough on methotrexate to satisfy our goal of getting the patient to low disease activity. It gives us as clinicians some ammunition to speak to our insurance formulary people on this side of the Atlantic, or [for] people in the U.K. to go to their local regulatory board that approves medicines and be able to show them some actual practically derived evidence about this very common question that comes up in practice,” senior and corresponding author Philip Mease, MD, said in an interview. The study was published online in The Lancet Rheumatology.

Mease_Philip_WA3_web.jpg

“When a clinician and patient are making the decision to move on from methotrexate monotherapy, either because of lack of efficacy or safety issues, tolerability issues, it makes most sense to add on a biologic medication such as a TNF inhibitor at that juncture, rather than intensifying methotrexate therapy,” said Dr. Mease, who is director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health and a clinical professor at the University of Washington, both in Seattle.

Physicians may be tempted to bump up the dose for patients who can tolerate MTX and who may be showing some improvement, but the new study should prompt a different strategy if MDA isn’t achieved, according to Oliver FitzGerald, MD, a professor at the Conway Institute for Biomolecular Research at University College Dublin, who was asked to comment on the study. “This study clearly shows that the early addition of adalimumab is the better choice, and it would change practice. That being said, there are clearly some patients who do respond sufficiently to increasing methotrexate, and it would be useful to be able to predict which patients might do that.” He added that the study focused on adalimumab and that the results might not apply to other biologics.

[embed:render:related:node:252563]

The study should encourage use of a quantitative treat-to-target measure like MDA, which is a composite measure of patient perspectives, Dr. Mease said. The American College of Rheumatology and National Psoriasis Foundation and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have recommended the use of MDA as a treat-to-target measure for PsA. The ACR and NPF recommend TNF inhibitors as first-line treatment, and GRAPPA includes it as a first-line option, whereas the European Alliance of Associations for Rheumatology recommends MTX only in the first line.

The study also suggests that there is value to using adalimumab on a weekly basis if an every-other-week schedule doesn’t produce the desired results. This strategy hasn’t been examined in PsA or even RA, according to Dr. Kavanaugh, who is a professor of medicine at the University of California, San Diego. “It did look like raising the dose might be an option for patients who are on every other week and are not doing quite as well as we would have hoped.”

The CONTROL study was a phase 4, two-part, open-label study. It included 245 patients in 14 countries who did not have MDA with MTX. In the first part of the study, patients were randomly assigned to receive weekly 15 mg MTX along with 40 mg adalimumab every other week, or escalation of MTX dose to 20-25 mg/week. MTX could be administered orally or intravenously. After 16 weeks (part 1), for patients who achieved MDA, current therapy was maintained or modified; for patients who did not achieve MDA, therapy was escalated over the following 16 weeks by giving adalimumab every week in the combination group or by adding adalimumab every other week in the MTX escalation arm.

Overall, 95% of the MTX plus adalimumab group completed part 1, as did 90% of the MTX escalation group. A total of 41% of the adalimumab group achieved MDA at 16 weeks versus 13% of the MTX group (P < .0001). The result held after accounting for sex and the interaction between sex and treatment (odds ratio, 4.6; 95% confidence interval, 2.4-8.9).

Among patients who achieved MDA at 16 weeks, 80% in the adalimumab group continued to have MDA at 32 weeks even after MTX had been withdrawn. Of those in the MTX escalation group, 67% continued to have MDA at 32 weeks with continued escalation of MTX.

[embed:render:related:node:178872]

Of the patients in the MTX escalation group who did not respond, 55% reached MDA following introduction of adalimumab every other week. Of those who did not respond to adalimumab, 30% reached MDA after switching to weekly adalimumab doses.

The study was open label, and patients who received adalimumab may have expected some improvement; that could have skewed the findings, Dr. Kavanaugh said. “I think that’s an important consideration as we interpret the data. The people who got the MTX arm probably had less of an expectation that they were going to do much better than those who switched to the adalimumab, as did the doctors taking care of them.”

The CONTROL study was funded by AbbVie. Dr. Mease has received research grants, consulted for, or received speaker honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB. Dr. FitzGerald has received grant support and honoraria from AbbVie. Dr. Kavanaugh has received research support from or consulted for AbbVie, Janssen, Pfizer, Lilly, Novartis, and UCB.

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

For patients with psoriatic arthritis (PsA) whose condition doesn’t respond adequately to methotrexate, addition of the tumor necrosis factor (TNF) inhibitor adalimumab increased the likelihood of achieving minimum disease activity (MDA), compared with escalation of MTX dose, according to results from a phase 4, open-label study.

The new study is one of only a few to compare treatment protocols in a field that has seen new therapeutic options become available in recent years. That lack of evidence can leave patients and physicians uncertain about the next step if the initial results of treatment are disappointing.

Kavanaugh_Arthur_CA_1_web.jpg

“There are some gaps in our database and our understanding of psoriatic arthritis, compared to rheumatoid arthritis, where we have had many more studies over the years,” Arthur Kavanaugh, MD, told this news organization when asked to comment on the study.

The trial provides one answer, at least. “There was a clear-cut signal that it made more sense to add adalimumab at that early juncture where a person is not quite doing well enough on methotrexate to satisfy our goal of getting the patient to low disease activity. It gives us as clinicians some ammunition to speak to our insurance formulary people on this side of the Atlantic, or [for] people in the U.K. to go to their local regulatory board that approves medicines and be able to show them some actual practically derived evidence about this very common question that comes up in practice,” senior and corresponding author Philip Mease, MD, said in an interview. The study was published online in The Lancet Rheumatology.

Mease_Philip_WA3_web.jpg

“When a clinician and patient are making the decision to move on from methotrexate monotherapy, either because of lack of efficacy or safety issues, tolerability issues, it makes most sense to add on a biologic medication such as a TNF inhibitor at that juncture, rather than intensifying methotrexate therapy,” said Dr. Mease, who is director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health and a clinical professor at the University of Washington, both in Seattle.

Physicians may be tempted to bump up the dose for patients who can tolerate MTX and who may be showing some improvement, but the new study should prompt a different strategy if MDA isn’t achieved, according to Oliver FitzGerald, MD, a professor at the Conway Institute for Biomolecular Research at University College Dublin, who was asked to comment on the study. “This study clearly shows that the early addition of adalimumab is the better choice, and it would change practice. That being said, there are clearly some patients who do respond sufficiently to increasing methotrexate, and it would be useful to be able to predict which patients might do that.” He added that the study focused on adalimumab and that the results might not apply to other biologics.

[embed:render:related:node:252563]

The study should encourage use of a quantitative treat-to-target measure like MDA, which is a composite measure of patient perspectives, Dr. Mease said. The American College of Rheumatology and National Psoriasis Foundation and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have recommended the use of MDA as a treat-to-target measure for PsA. The ACR and NPF recommend TNF inhibitors as first-line treatment, and GRAPPA includes it as a first-line option, whereas the European Alliance of Associations for Rheumatology recommends MTX only in the first line.

The study also suggests that there is value to using adalimumab on a weekly basis if an every-other-week schedule doesn’t produce the desired results. This strategy hasn’t been examined in PsA or even RA, according to Dr. Kavanaugh, who is a professor of medicine at the University of California, San Diego. “It did look like raising the dose might be an option for patients who are on every other week and are not doing quite as well as we would have hoped.”

The CONTROL study was a phase 4, two-part, open-label study. It included 245 patients in 14 countries who did not have MDA with MTX. In the first part of the study, patients were randomly assigned to receive weekly 15 mg MTX along with 40 mg adalimumab every other week, or escalation of MTX dose to 20-25 mg/week. MTX could be administered orally or intravenously. After 16 weeks (part 1), for patients who achieved MDA, current therapy was maintained or modified; for patients who did not achieve MDA, therapy was escalated over the following 16 weeks by giving adalimumab every week in the combination group or by adding adalimumab every other week in the MTX escalation arm.

Overall, 95% of the MTX plus adalimumab group completed part 1, as did 90% of the MTX escalation group. A total of 41% of the adalimumab group achieved MDA at 16 weeks versus 13% of the MTX group (P < .0001). The result held after accounting for sex and the interaction between sex and treatment (odds ratio, 4.6; 95% confidence interval, 2.4-8.9).

Among patients who achieved MDA at 16 weeks, 80% in the adalimumab group continued to have MDA at 32 weeks even after MTX had been withdrawn. Of those in the MTX escalation group, 67% continued to have MDA at 32 weeks with continued escalation of MTX.

[embed:render:related:node:178872]

Of the patients in the MTX escalation group who did not respond, 55% reached MDA following introduction of adalimumab every other week. Of those who did not respond to adalimumab, 30% reached MDA after switching to weekly adalimumab doses.

The study was open label, and patients who received adalimumab may have expected some improvement; that could have skewed the findings, Dr. Kavanaugh said. “I think that’s an important consideration as we interpret the data. The people who got the MTX arm probably had less of an expectation that they were going to do much better than those who switched to the adalimumab, as did the doctors taking care of them.”

The CONTROL study was funded by AbbVie. Dr. Mease has received research grants, consulted for, or received speaker honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB. Dr. FitzGerald has received grant support and honoraria from AbbVie. Dr. Kavanaugh has received research support from or consulted for AbbVie, Janssen, Pfizer, Lilly, Novartis, and UCB.

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

For patients with psoriatic arthritis (PsA) whose condition doesn’t respond adequately to methotrexate, addition of the tumor necrosis factor (TNF) inhibitor adalimumab increased the likelihood of achieving minimum disease activity (MDA), compared with escalation of MTX dose, according to results from a phase 4, open-label study.

The new study is one of only a few to compare treatment protocols in a field that has seen new therapeutic options become available in recent years. That lack of evidence can leave patients and physicians uncertain about the next step if the initial results of treatment are disappointing.

Kavanaugh_Arthur_CA_1_web.jpg

“There are some gaps in our database and our understanding of psoriatic arthritis, compared to rheumatoid arthritis, where we have had many more studies over the years,” Arthur Kavanaugh, MD, told this news organization when asked to comment on the study.

The trial provides one answer, at least. “There was a clear-cut signal that it made more sense to add adalimumab at that early juncture where a person is not quite doing well enough on methotrexate to satisfy our goal of getting the patient to low disease activity. It gives us as clinicians some ammunition to speak to our insurance formulary people on this side of the Atlantic, or [for] people in the U.K. to go to their local regulatory board that approves medicines and be able to show them some actual practically derived evidence about this very common question that comes up in practice,” senior and corresponding author Philip Mease, MD, said in an interview. The study was published online in The Lancet Rheumatology.

Mease_Philip_WA3_web.jpg

“When a clinician and patient are making the decision to move on from methotrexate monotherapy, either because of lack of efficacy or safety issues, tolerability issues, it makes most sense to add on a biologic medication such as a TNF inhibitor at that juncture, rather than intensifying methotrexate therapy,” said Dr. Mease, who is director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health and a clinical professor at the University of Washington, both in Seattle.

Physicians may be tempted to bump up the dose for patients who can tolerate MTX and who may be showing some improvement, but the new study should prompt a different strategy if MDA isn’t achieved, according to Oliver FitzGerald, MD, a professor at the Conway Institute for Biomolecular Research at University College Dublin, who was asked to comment on the study. “This study clearly shows that the early addition of adalimumab is the better choice, and it would change practice. That being said, there are clearly some patients who do respond sufficiently to increasing methotrexate, and it would be useful to be able to predict which patients might do that.” He added that the study focused on adalimumab and that the results might not apply to other biologics.

[embed:render:related:node:252563]

The study should encourage use of a quantitative treat-to-target measure like MDA, which is a composite measure of patient perspectives, Dr. Mease said. The American College of Rheumatology and National Psoriasis Foundation and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have recommended the use of MDA as a treat-to-target measure for PsA. The ACR and NPF recommend TNF inhibitors as first-line treatment, and GRAPPA includes it as a first-line option, whereas the European Alliance of Associations for Rheumatology recommends MTX only in the first line.

The study also suggests that there is value to using adalimumab on a weekly basis if an every-other-week schedule doesn’t produce the desired results. This strategy hasn’t been examined in PsA or even RA, according to Dr. Kavanaugh, who is a professor of medicine at the University of California, San Diego. “It did look like raising the dose might be an option for patients who are on every other week and are not doing quite as well as we would have hoped.”

The CONTROL study was a phase 4, two-part, open-label study. It included 245 patients in 14 countries who did not have MDA with MTX. In the first part of the study, patients were randomly assigned to receive weekly 15 mg MTX along with 40 mg adalimumab every other week, or escalation of MTX dose to 20-25 mg/week. MTX could be administered orally or intravenously. After 16 weeks (part 1), for patients who achieved MDA, current therapy was maintained or modified; for patients who did not achieve MDA, therapy was escalated over the following 16 weeks by giving adalimumab every week in the combination group or by adding adalimumab every other week in the MTX escalation arm.

Overall, 95% of the MTX plus adalimumab group completed part 1, as did 90% of the MTX escalation group. A total of 41% of the adalimumab group achieved MDA at 16 weeks versus 13% of the MTX group (P < .0001). The result held after accounting for sex and the interaction between sex and treatment (odds ratio, 4.6; 95% confidence interval, 2.4-8.9).

Among patients who achieved MDA at 16 weeks, 80% in the adalimumab group continued to have MDA at 32 weeks even after MTX had been withdrawn. Of those in the MTX escalation group, 67% continued to have MDA at 32 weeks with continued escalation of MTX.

[embed:render:related:node:178872]

Of the patients in the MTX escalation group who did not respond, 55% reached MDA following introduction of adalimumab every other week. Of those who did not respond to adalimumab, 30% reached MDA after switching to weekly adalimumab doses.

The study was open label, and patients who received adalimumab may have expected some improvement; that could have skewed the findings, Dr. Kavanaugh said. “I think that’s an important consideration as we interpret the data. The people who got the MTX arm probably had less of an expectation that they were going to do much better than those who switched to the adalimumab, as did the doctors taking care of them.”

The CONTROL study was funded by AbbVie. Dr. Mease has received research grants, consulted for, or received speaker honoraria from AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB. Dr. FitzGerald has received grant support and honoraria from AbbVie. Dr. Kavanaugh has received research support from or consulted for AbbVie, Janssen, Pfizer, Lilly, Novartis, and UCB.

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

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

[embed:render:related:node:229520]

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

[embed:render:related:node:229520]

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

[embed:render:related:node:229520]

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

A new study has found that methotrexate plus leflunomide outperforms methotrexate alone as a treatment option for patients with psoriatic arthritis (PsA).

“We believe that prescribing this combination in routine practice is viable when combined with shared decision-making and strict monitoring of side effects,” write Michelle L.M. Mulder, MD, of the department of rheumatology at Sint Maartenskliniek in Nijmegen, the Netherlands, and her coauthors. Their findings were published in The Lancet Rheumatology.

Mulder_Michelle_NETHERLANDS_web.jpg

The latest treatment guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European Alliance of Associations for Rheumatology recommend conventional synthetic disease-modifying antirheumatic drugs for patients with active PsA, but Dr. Mulder and her colleagues note a distinct lack of information on their effectiveness, especially this particular combination.

To assess the efficacy and safety of methotrexate plus leflunomide, they launched a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA. The majority of the participants in this trial – dubbed COMPLETE-PsA – were men (64%), and the median age of the patients was 55 years. All had active disease at baseline; the median swollen joint count (SJC) and tender joint count were 4.0 in both groups.

Participants were assigned to receive either methotrexate plus leflunomide (n = 39) or methotrexate plus placebo (n = 39). 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, 1.4 vs. 3.7; SD, 1.3; treatment difference, –0.6; 90% confidence interval, –1.0 to –0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than did the monotherapy group (34%; P = .019).

Other notable differences after 16 weeks included improvements in SJC for 66 joints (–3.0 in the combination therapy group vs. –2.0 in the monotherapy group) and significantly better skin and nail measures – such as active psoriasis and change in body surface area – in the methotrexate plus leflunomide group.

[embed:render:related:node:241185]

When asked who should be prescribed the combination therapy and who should be prescribed methotrexate going forward, Dr. Mulder told this news organization, “At the moment, we have insufficient knowledge on who will benefit most or who will develop clinically relevant side effects. It seems warranted to discuss with every patient which approach they would prefer. This could be a step-down or -up approach.

“We hope to be able to better predict treatment response and side effects in the future via post hoc analysis of our study and via extensive flow-cytometric phenotyping of immune blood cells taken at baseline,” she added.

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. No participants died, and all patients with adverse events recovered completely.

“It appears good practice to do blood draws for laboratory tests on liver enzymes at least monthly for the first 4 months and every 4 months after that once stable dosing is achieved, as well as have a telephone consultation after 6-8 weeks to talk about possible side effects a patient might experience and change or add therapy if necessary,” Dr. Mulder added.

Study turns perception of combination therapy into reality

It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.

They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.

[embed:render:related:node:203922]

“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”

The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”

Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”

Leflunomide: Forgotten no longer, at least for PsA

“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.

Kavanaugh_Arthur_CA_1_web.jpg

“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”

Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.

“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.

“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”

The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”

The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.

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

A new study has found that methotrexate plus leflunomide outperforms methotrexate alone as a treatment option for patients with psoriatic arthritis (PsA).

“We believe that prescribing this combination in routine practice is viable when combined with shared decision-making and strict monitoring of side effects,” write Michelle L.M. Mulder, MD, of the department of rheumatology at Sint Maartenskliniek in Nijmegen, the Netherlands, and her coauthors. Their findings were published in The Lancet Rheumatology.

Mulder_Michelle_NETHERLANDS_web.jpg

The latest treatment guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European Alliance of Associations for Rheumatology recommend conventional synthetic disease-modifying antirheumatic drugs for patients with active PsA, but Dr. Mulder and her colleagues note a distinct lack of information on their effectiveness, especially this particular combination.

To assess the efficacy and safety of methotrexate plus leflunomide, they launched a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA. The majority of the participants in this trial – dubbed COMPLETE-PsA – were men (64%), and the median age of the patients was 55 years. All had active disease at baseline; the median swollen joint count (SJC) and tender joint count were 4.0 in both groups.

Participants were assigned to receive either methotrexate plus leflunomide (n = 39) or methotrexate plus placebo (n = 39). 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, 1.4 vs. 3.7; SD, 1.3; treatment difference, –0.6; 90% confidence interval, –1.0 to –0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than did the monotherapy group (34%; P = .019).

Other notable differences after 16 weeks included improvements in SJC for 66 joints (–3.0 in the combination therapy group vs. –2.0 in the monotherapy group) and significantly better skin and nail measures – such as active psoriasis and change in body surface area – in the methotrexate plus leflunomide group.

[embed:render:related:node:241185]

When asked who should be prescribed the combination therapy and who should be prescribed methotrexate going forward, Dr. Mulder told this news organization, “At the moment, we have insufficient knowledge on who will benefit most or who will develop clinically relevant side effects. It seems warranted to discuss with every patient which approach they would prefer. This could be a step-down or -up approach.

“We hope to be able to better predict treatment response and side effects in the future via post hoc analysis of our study and via extensive flow-cytometric phenotyping of immune blood cells taken at baseline,” she added.

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. No participants died, and all patients with adverse events recovered completely.

“It appears good practice to do blood draws for laboratory tests on liver enzymes at least monthly for the first 4 months and every 4 months after that once stable dosing is achieved, as well as have a telephone consultation after 6-8 weeks to talk about possible side effects a patient might experience and change or add therapy if necessary,” Dr. Mulder added.

Study turns perception of combination therapy into reality

It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.

They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.

[embed:render:related:node:203922]

“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”

The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”

Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”

Leflunomide: Forgotten no longer, at least for PsA

“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.

Kavanaugh_Arthur_CA_1_web.jpg

“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”

Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.

“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.

“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”

The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”

The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.

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

A new study has found that methotrexate plus leflunomide outperforms methotrexate alone as a treatment option for patients with psoriatic arthritis (PsA).

“We believe that prescribing this combination in routine practice is viable when combined with shared decision-making and strict monitoring of side effects,” write Michelle L.M. Mulder, MD, of the department of rheumatology at Sint Maartenskliniek in Nijmegen, the Netherlands, and her coauthors. Their findings were published in The Lancet Rheumatology.

Mulder_Michelle_NETHERLANDS_web.jpg

The latest treatment guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European Alliance of Associations for Rheumatology recommend conventional synthetic disease-modifying antirheumatic drugs for patients with active PsA, but Dr. Mulder and her colleagues note a distinct lack of information on their effectiveness, especially this particular combination.

To assess the efficacy and safety of methotrexate plus leflunomide, they launched a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA. The majority of the participants in this trial – dubbed COMPLETE-PsA – were men (64%), and the median age of the patients was 55 years. All had active disease at baseline; the median swollen joint count (SJC) and tender joint count were 4.0 in both groups.

Participants were assigned to receive either methotrexate plus leflunomide (n = 39) or methotrexate plus placebo (n = 39). 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, 1.4 vs. 3.7; SD, 1.3; treatment difference, –0.6; 90% confidence interval, –1.0 to –0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than did the monotherapy group (34%; P = .019).

Other notable differences after 16 weeks included improvements in SJC for 66 joints (–3.0 in the combination therapy group vs. –2.0 in the monotherapy group) and significantly better skin and nail measures – such as active psoriasis and change in body surface area – in the methotrexate plus leflunomide group.

[embed:render:related:node:241185]

When asked who should be prescribed the combination therapy and who should be prescribed methotrexate going forward, Dr. Mulder told this news organization, “At the moment, we have insufficient knowledge on who will benefit most or who will develop clinically relevant side effects. It seems warranted to discuss with every patient which approach they would prefer. This could be a step-down or -up approach.

“We hope to be able to better predict treatment response and side effects in the future via post hoc analysis of our study and via extensive flow-cytometric phenotyping of immune blood cells taken at baseline,” she added.

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. No participants died, and all patients with adverse events recovered completely.

“It appears good practice to do blood draws for laboratory tests on liver enzymes at least monthly for the first 4 months and every 4 months after that once stable dosing is achieved, as well as have a telephone consultation after 6-8 weeks to talk about possible side effects a patient might experience and change or add therapy if necessary,” Dr. Mulder added.

Study turns perception of combination therapy into reality

It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.

They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.

[embed:render:related:node:203922]

“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”

The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”

Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”

Leflunomide: Forgotten no longer, at least for PsA

“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.

Kavanaugh_Arthur_CA_1_web.jpg

“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”

Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.

“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.

“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”

The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”

The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.

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

The Food and Drug Administration on Jan. 21 approved risankizumab-rzaa (Skyrizi) for a second indication – treating adults with active psoriatic arthritis (PsA) – making it the second anti–interleukin-23 monoclonal antibody available to treat PsA, according to an announcement from manufacturer AbbVie.

The agency previously approved risankizumab in April 2019 for adults with moderate to severe plaque psoriasis.

[embed:render:related:node:224333]

The dosing regimen for PsA is the same as it is for patients with moderate to severe plaque psoriasis: a single 150-mg subcutaneous injection four times a year (after two starter doses at weeks 0 and 4), and it can be administered alone or in combination with disease-modifying antirheumatic drugs (DMARDs).

Two phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2, were the basis for the approval. These two trials tested the biologic agent in adults with active PsA, including those who had responded inadequately or were intolerant to biologic therapy and/or nonbiologic DMARDs. Fulfillment of the trials’ primary endpoint of at least a 20% improvement in American College of Rheumatology response criteria at 24 weeks occurred in 51.3%-57.3% of patients, compared with 26.5%-33.5% of placebo-treated patients.

Those on risankizumab also achieved significantly higher rates of ACR50 and ACR70 responses than those on placebo. In addition, patients with preexisting dactylitis and enthesitis experienced improvements in these PsA manifestations. Risankizumab was also associated with an improvement in physical function at 24 weeks on the Health Assessment Questionnaire–Disability Index, bettering placebo by a mean difference of 0.16-0.20 points in the two trials. A significantly higher percentage of patients who had psoriatic skin lesions experienced at least 90% improvement with risankizumab on the Psoriasis Area and Severity Index, compared with placebo.

AbbVie said that the safety profile of risankizumab in patients with PsA has been generally consistent with its effects in patients with plaque psoriasis.

[embed:render:related:node:248387]

The KEEPsAKE 1 and KEEPsAKE 2 studies are ongoing, and patients in the long-term extensions of the trials remain blinded to the original randomized allocation for the duration of the studies.

Phase 3 trials of risankizumab are also ongoing in patients with Crohn’s disease and ulcerative colitis.

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

The Food and Drug Administration on Jan. 21 approved risankizumab-rzaa (Skyrizi) for a second indication – treating adults with active psoriatic arthritis (PsA) – making it the second anti–interleukin-23 monoclonal antibody available to treat PsA, according to an announcement from manufacturer AbbVie.

The agency previously approved risankizumab in April 2019 for adults with moderate to severe plaque psoriasis.

[embed:render:related:node:224333]

The dosing regimen for PsA is the same as it is for patients with moderate to severe plaque psoriasis: a single 150-mg subcutaneous injection four times a year (after two starter doses at weeks 0 and 4), and it can be administered alone or in combination with disease-modifying antirheumatic drugs (DMARDs).

Two phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2, were the basis for the approval. These two trials tested the biologic agent in adults with active PsA, including those who had responded inadequately or were intolerant to biologic therapy and/or nonbiologic DMARDs. Fulfillment of the trials’ primary endpoint of at least a 20% improvement in American College of Rheumatology response criteria at 24 weeks occurred in 51.3%-57.3% of patients, compared with 26.5%-33.5% of placebo-treated patients.

Those on risankizumab also achieved significantly higher rates of ACR50 and ACR70 responses than those on placebo. In addition, patients with preexisting dactylitis and enthesitis experienced improvements in these PsA manifestations. Risankizumab was also associated with an improvement in physical function at 24 weeks on the Health Assessment Questionnaire–Disability Index, bettering placebo by a mean difference of 0.16-0.20 points in the two trials. A significantly higher percentage of patients who had psoriatic skin lesions experienced at least 90% improvement with risankizumab on the Psoriasis Area and Severity Index, compared with placebo.

AbbVie said that the safety profile of risankizumab in patients with PsA has been generally consistent with its effects in patients with plaque psoriasis.

[embed:render:related:node:248387]

The KEEPsAKE 1 and KEEPsAKE 2 studies are ongoing, and patients in the long-term extensions of the trials remain blinded to the original randomized allocation for the duration of the studies.

Phase 3 trials of risankizumab are also ongoing in patients with Crohn’s disease and ulcerative colitis.

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

The Food and Drug Administration on Jan. 21 approved risankizumab-rzaa (Skyrizi) for a second indication – treating adults with active psoriatic arthritis (PsA) – making it the second anti–interleukin-23 monoclonal antibody available to treat PsA, according to an announcement from manufacturer AbbVie.

The agency previously approved risankizumab in April 2019 for adults with moderate to severe plaque psoriasis.

[embed:render:related:node:224333]

The dosing regimen for PsA is the same as it is for patients with moderate to severe plaque psoriasis: a single 150-mg subcutaneous injection four times a year (after two starter doses at weeks 0 and 4), and it can be administered alone or in combination with disease-modifying antirheumatic drugs (DMARDs).

Two phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2, were the basis for the approval. These two trials tested the biologic agent in adults with active PsA, including those who had responded inadequately or were intolerant to biologic therapy and/or nonbiologic DMARDs. Fulfillment of the trials’ primary endpoint of at least a 20% improvement in American College of Rheumatology response criteria at 24 weeks occurred in 51.3%-57.3% of patients, compared with 26.5%-33.5% of placebo-treated patients.

Those on risankizumab also achieved significantly higher rates of ACR50 and ACR70 responses than those on placebo. In addition, patients with preexisting dactylitis and enthesitis experienced improvements in these PsA manifestations. Risankizumab was also associated with an improvement in physical function at 24 weeks on the Health Assessment Questionnaire–Disability Index, bettering placebo by a mean difference of 0.16-0.20 points in the two trials. A significantly higher percentage of patients who had psoriatic skin lesions experienced at least 90% improvement with risankizumab on the Psoriasis Area and Severity Index, compared with placebo.

AbbVie said that the safety profile of risankizumab in patients with PsA has been generally consistent with its effects in patients with plaque psoriasis.

[embed:render:related:node:248387]

The KEEPsAKE 1 and KEEPsAKE 2 studies are ongoing, and patients in the long-term extensions of the trials remain blinded to the original randomized allocation for the duration of the studies.

Phase 3 trials of risankizumab are also ongoing in patients with Crohn’s disease and ulcerative colitis.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

blood_draw_web.jpg

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

Vande_Casteele_Niels_CA_web.jpg

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

Syversen_Silje_NORWAY_web.jpg

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

[embed:render:related:node:229002]

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

Sparks_Jeffrey_A_MA_web.jpg

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

Wallace_Zachary_BOSTON_web.jpg

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

blood_draw_web.jpg

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

Vande_Casteele_Niels_CA_web.jpg

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

Syversen_Silje_NORWAY_web.jpg

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

[embed:render:related:node:229002]

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

Sparks_Jeffrey_A_MA_web.jpg

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

Wallace_Zachary_BOSTON_web.jpg

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

blood_draw_web.jpg

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

Vande_Casteele_Niels_CA_web.jpg

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

Syversen_Silje_NORWAY_web.jpg

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

[embed:render:related:node:229002]

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

Sparks_Jeffrey_A_MA_web.jpg

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

Wallace_Zachary_BOSTON_web.jpg

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

The rate of U.S. hospitalizations for three types of serious infections in patients with psoriatic arthritis (PsA) appears to have declined from 2012 to 2017, according to research presented at the virtual annual meeting of the American College of Rheumatology.

Several of the standard treatments for PsA have an increased risk of infections, but the rates vary amongst conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologics, and other therapies.

“Given the uptake of biological therapies has increased over recent years, we sought to investigate the national trends in serious infections in patients with psoriatic arthritis from the years 2012 to 2017,” Vagishwari Murugesan, MBBS, a psoriatic arthritis clinical fellow at the University of Toronto, told attendees in a prerecorded poster presentation. Dr. Murugesan was a fellow at Boston University when she conducted the research.

The researchers analyzed data from 2012 to 2017 in the U.S. National Inpatient Sample (NIS), which includes approximately 20% of all discharges from U.S. community hospitals except rehabilitation and long-term acute care institutions. Using ICD-9 and ICD-10 codes, the researchers identified all discharge records containing a diagnosis of PsA as well as pneumonia, sepsis, urinary tract infection (UTI), and skin and soft-tissue infections. After making adjustments to match U.S. population age distributions over the years, they examined trends in serious infections among patients with PsA for that 6-year period.

[embed:render:related:node:211730]

Demographics over those years changed little: The average age of discharged patients was 59.5 in 2012 and 60.8 in 2017. Similarly, the patient population was 56% women and 88.5% Whites in 2012 and 57.7% women and 88.4% Whites in 2017. The average length of stay was also similar: 4.7 days in 2012, compared with 4.9 days in 2017.

Among 50,700 discharges of patients with PsA in 2012, the researchers identified 125 with pneumonia, 230 with sepsis, 312 with skin and soft-tissue infections, and 174 with a UTI. Among the 179,400 discharges in 2017 of patients with PsA, 344 had pneumonia, 374 had sepsis, 681 had skin and soft-tissue infections, and 348 had a UTI. After statistical analysis, the researchers found no significant differences in pneumonia diagnoses during the years studied, but they did find a statistically significant decline in sepsis, skin and soft tissue infections, and UTI discharges (P < .001).

A notable limitation of the study is the NIS database’s lack of data on treatments or outpatient data, making it impossible to determine if more infections were occurring but simply being treated in outpatient settings, although it’s not clear why such a substantial shift would occur in just 5 years. It’s also possible that coding practices differ across hospital, but, presumably, the ways they might differ in 2012 would be similar to any differences in 2017.

Kavanaugh_Arthur_CA_1_web.jpg

Arthur Kavanaugh, MD, a professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, found the results interesting for what he considers an important topic.

“What makes these data interesting is the same thing that limits their reliability: The authors note that infections decreased ‘despite the increase in use of biologics over this time,’ ” Dr. Kavanaugh said in an interview. “These are claims data, so there is no way to support any association between those serious infections and biologic use. Indeed, multiple factors could have also impacted these data. It is not possible to tell from claims data.”

[embed:render:related:node:229520]

Dr. Kavanaugh said the question is worth investigating further with data from other sources.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One study coauthor reported ties to UCB; Dr. Murugesan and her other coauthors reported no disclosures. Dr. Kavanaugh had no disclosures.

The rate of U.S. hospitalizations for three types of serious infections in patients with psoriatic arthritis (PsA) appears to have declined from 2012 to 2017, according to research presented at the virtual annual meeting of the American College of Rheumatology.

Several of the standard treatments for PsA have an increased risk of infections, but the rates vary amongst conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologics, and other therapies.

“Given the uptake of biological therapies has increased over recent years, we sought to investigate the national trends in serious infections in patients with psoriatic arthritis from the years 2012 to 2017,” Vagishwari Murugesan, MBBS, a psoriatic arthritis clinical fellow at the University of Toronto, told attendees in a prerecorded poster presentation. Dr. Murugesan was a fellow at Boston University when she conducted the research.

The researchers analyzed data from 2012 to 2017 in the U.S. National Inpatient Sample (NIS), which includes approximately 20% of all discharges from U.S. community hospitals except rehabilitation and long-term acute care institutions. Using ICD-9 and ICD-10 codes, the researchers identified all discharge records containing a diagnosis of PsA as well as pneumonia, sepsis, urinary tract infection (UTI), and skin and soft-tissue infections. After making adjustments to match U.S. population age distributions over the years, they examined trends in serious infections among patients with PsA for that 6-year period.

[embed:render:related:node:211730]

Demographics over those years changed little: The average age of discharged patients was 59.5 in 2012 and 60.8 in 2017. Similarly, the patient population was 56% women and 88.5% Whites in 2012 and 57.7% women and 88.4% Whites in 2017. The average length of stay was also similar: 4.7 days in 2012, compared with 4.9 days in 2017.

Among 50,700 discharges of patients with PsA in 2012, the researchers identified 125 with pneumonia, 230 with sepsis, 312 with skin and soft-tissue infections, and 174 with a UTI. Among the 179,400 discharges in 2017 of patients with PsA, 344 had pneumonia, 374 had sepsis, 681 had skin and soft-tissue infections, and 348 had a UTI. After statistical analysis, the researchers found no significant differences in pneumonia diagnoses during the years studied, but they did find a statistically significant decline in sepsis, skin and soft tissue infections, and UTI discharges (P < .001).

A notable limitation of the study is the NIS database’s lack of data on treatments or outpatient data, making it impossible to determine if more infections were occurring but simply being treated in outpatient settings, although it’s not clear why such a substantial shift would occur in just 5 years. It’s also possible that coding practices differ across hospital, but, presumably, the ways they might differ in 2012 would be similar to any differences in 2017.

Kavanaugh_Arthur_CA_1_web.jpg

Arthur Kavanaugh, MD, a professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, found the results interesting for what he considers an important topic.

“What makes these data interesting is the same thing that limits their reliability: The authors note that infections decreased ‘despite the increase in use of biologics over this time,’ ” Dr. Kavanaugh said in an interview. “These are claims data, so there is no way to support any association between those serious infections and biologic use. Indeed, multiple factors could have also impacted these data. It is not possible to tell from claims data.”

[embed:render:related:node:229520]

Dr. Kavanaugh said the question is worth investigating further with data from other sources.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One study coauthor reported ties to UCB; Dr. Murugesan and her other coauthors reported no disclosures. Dr. Kavanaugh had no disclosures.

The rate of U.S. hospitalizations for three types of serious infections in patients with psoriatic arthritis (PsA) appears to have declined from 2012 to 2017, according to research presented at the virtual annual meeting of the American College of Rheumatology.

Several of the standard treatments for PsA have an increased risk of infections, but the rates vary amongst conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologics, and other therapies.

“Given the uptake of biological therapies has increased over recent years, we sought to investigate the national trends in serious infections in patients with psoriatic arthritis from the years 2012 to 2017,” Vagishwari Murugesan, MBBS, a psoriatic arthritis clinical fellow at the University of Toronto, told attendees in a prerecorded poster presentation. Dr. Murugesan was a fellow at Boston University when she conducted the research.

The researchers analyzed data from 2012 to 2017 in the U.S. National Inpatient Sample (NIS), which includes approximately 20% of all discharges from U.S. community hospitals except rehabilitation and long-term acute care institutions. Using ICD-9 and ICD-10 codes, the researchers identified all discharge records containing a diagnosis of PsA as well as pneumonia, sepsis, urinary tract infection (UTI), and skin and soft-tissue infections. After making adjustments to match U.S. population age distributions over the years, they examined trends in serious infections among patients with PsA for that 6-year period.

[embed:render:related:node:211730]

Demographics over those years changed little: The average age of discharged patients was 59.5 in 2012 and 60.8 in 2017. Similarly, the patient population was 56% women and 88.5% Whites in 2012 and 57.7% women and 88.4% Whites in 2017. The average length of stay was also similar: 4.7 days in 2012, compared with 4.9 days in 2017.

Among 50,700 discharges of patients with PsA in 2012, the researchers identified 125 with pneumonia, 230 with sepsis, 312 with skin and soft-tissue infections, and 174 with a UTI. Among the 179,400 discharges in 2017 of patients with PsA, 344 had pneumonia, 374 had sepsis, 681 had skin and soft-tissue infections, and 348 had a UTI. After statistical analysis, the researchers found no significant differences in pneumonia diagnoses during the years studied, but they did find a statistically significant decline in sepsis, skin and soft tissue infections, and UTI discharges (P < .001).

A notable limitation of the study is the NIS database’s lack of data on treatments or outpatient data, making it impossible to determine if more infections were occurring but simply being treated in outpatient settings, although it’s not clear why such a substantial shift would occur in just 5 years. It’s also possible that coding practices differ across hospital, but, presumably, the ways they might differ in 2012 would be similar to any differences in 2017.

Kavanaugh_Arthur_CA_1_web.jpg

Arthur Kavanaugh, MD, a professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, found the results interesting for what he considers an important topic.

“What makes these data interesting is the same thing that limits their reliability: The authors note that infections decreased ‘despite the increase in use of biologics over this time,’ ” Dr. Kavanaugh said in an interview. “These are claims data, so there is no way to support any association between those serious infections and biologic use. Indeed, multiple factors could have also impacted these data. It is not possible to tell from claims data.”

[embed:render:related:node:229520]

Dr. Kavanaugh said the question is worth investigating further with data from other sources.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One study coauthor reported ties to UCB; Dr. Murugesan and her other coauthors reported no disclosures. Dr. Kavanaugh had no disclosures.