Psoriatic Arthritis

PARIS – The interleukin-17 receptor inhibitor brodalumab achieved complete clearance of moderate-to-severe psoriasis far faster and more frequently than the interleukin-12/23 inhibitor ustekinumab.

Bruce Jancin/MDedge News

That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.

“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.

Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.

“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”

His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.

It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.

This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.

Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.

The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.

Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.

[email protected]

SOURCE: Reich K. EADV Congress, Abstract #FC03.06.

PARIS – The interleukin-17 receptor inhibitor brodalumab achieved complete clearance of moderate-to-severe psoriasis far faster and more frequently than the interleukin-12/23 inhibitor ustekinumab.

Bruce Jancin/MDedge News

That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.

“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.

Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.

“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”

His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.

It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.

This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.

Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.

The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.

Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.

[email protected]

SOURCE: Reich K. EADV Congress, Abstract #FC03.06.

PARIS – The interleukin-17 receptor inhibitor brodalumab achieved complete clearance of moderate-to-severe psoriasis far faster and more frequently than the interleukin-12/23 inhibitor ustekinumab.

Bruce Jancin/MDedge News

That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.

“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.

Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.

“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”

His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.

It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.

This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.

Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.

The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.

Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.

[email protected]

SOURCE: Reich K. EADV Congress, Abstract #FC03.06.

PARIS – Dermatologists are likely to do a double-take when they see the long-term efficacy and safety data for tildrakizumab (Ilumya), a high-affinity humanized monoclonal antibody targeting interleukin-23 p19, relative to the performance of older and more familiar biologic agents with other targets in psoriasis, Diamant Thaçi, MD, predicted at the annual congress of the European Academy of Dermatology and Venereology.

“The time to relapse [off tildrakizumab] is very different from what we are used to with other biologics; for example, the tumor necrosis factor inhibitors,” observed Dr. Thaçi, professor and chairman of the department of dermatology at the University of Lübeck (Germany).

He presented the 148-week, follow-up results of a pooled analysis of the open-label extension studies of reSURFACE 1 and reSURFACE 2, two pivotal phase 3 randomized double-blind international trials of 1,862 patients with moderate to severe chronic plaque psoriasis. The primary outcomes through week 12, which were instrumental in gaining marketing approval for tildrakizumab for treating psoriasis in 2018 from the Food and Drug Administration and the European Medicines Agency, have been published in the Lancet (2017 Jul 15;390[10091]:276-88).

Dr. Thaçi’s analysis of the 148-week outcomes was restricted to the patients who had at least a 75% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 75) at week 28. Nearly 80% of patients on tildrakizumab reached that threshold at week 28 in reSURFACE 1, as did 73% in reSURFACE 2.

The question asked in the extension study was, How do responders to tildrakizumab at 28 weeks fare after nearly 3 years on the drug? And the answer was: very well. Maintenance of at least a PASI 75 response was observed at 148 weeks in 91% of patients on tildrakizumab at the approved 100-mg dose and 92% of those on the 200-mg dose. The FDA-approved regimen is 100 mg by subcutaneous injection at weeks 0 and 4, and then every 12 weeks after that.

An intriguing feature of reSURFACE 1 was that a subset of PASI 75 responders at week 28 got taken off tildrakizumab at that point and switched to double-blind placebo, then restarted on their earlier dose of tildrakizumab upon relapse, which was defined as loss of at least 50% of the achieved on-drug PASI improvement.

At week 64, fully 48 weeks after their last dose of tildrakizumab, the relapse rate was 54% in the group formerly on 100 mg of tildrakizumab and slightly better at 47% in those formerly on 200 mg. The median time to relapse was 226 days in the 100-mg group and 258 days in the higher-dose arm. Those are exceptionally long times to relapse, and it’s useful information to file away in the event a psoriasis patient needs to discontinue biologic therapy for a period of time, Dr. Thaçi observed.

At week 64 – again, off active treatment since week 16 – 63% of the tildrakizumab 100-mg group had lost their previous PASI 75 response, as had 52% who were formerly on tildrakizumab at 200 mg.

The long-term safety profile of tildrakizumab paralleled that of placebo. For example, the exposure-adjusted adverse event rates of serious infections and major adverse cardiovascular events were closely similar in the placebo, tildrakizumab 100 mg, and tildrakizumab 200 mg groups.

There were two notable between-group differences in adverse events of interest: injection site reactions occurred at a rate of 5.36 per 100 person-years with placebo, compared with 1.94 and 2.3 per 100 person-years with tildrakizumab at 100 and 200 mg, respectively; and the incidence of nonmelanoma skin cancer was 0.97 cases per 100 person-years in the placebo arm, versus 0.5 and 0.49 cases per 100 person-years in the two tildrakizumab arms.

Dr. Thaçi did not present PASI 90 response outcomes because, at the time the reSURFACE trials were planned, PASI 75 was considered state of the art. The PASI 90 data are still being crunched but will be available soon. The 4- and 5-year follow-up data from the long-term extension studies are also on their way.

The reSURFACE 1 and reSURFACE 2 trials and their extension studies were funded by Sun Pharma and Merck. Dr. Thaçi reported receiving research grants from and serving as a consultant and paid scientific advisor to those pharmaceutical companies and more than a dozen others.

PARIS – Dermatologists are likely to do a double-take when they see the long-term efficacy and safety data for tildrakizumab (Ilumya), a high-affinity humanized monoclonal antibody targeting interleukin-23 p19, relative to the performance of older and more familiar biologic agents with other targets in psoriasis, Diamant Thaçi, MD, predicted at the annual congress of the European Academy of Dermatology and Venereology.

“The time to relapse [off tildrakizumab] is very different from what we are used to with other biologics; for example, the tumor necrosis factor inhibitors,” observed Dr. Thaçi, professor and chairman of the department of dermatology at the University of Lübeck (Germany).

He presented the 148-week, follow-up results of a pooled analysis of the open-label extension studies of reSURFACE 1 and reSURFACE 2, two pivotal phase 3 randomized double-blind international trials of 1,862 patients with moderate to severe chronic plaque psoriasis. The primary outcomes through week 12, which were instrumental in gaining marketing approval for tildrakizumab for treating psoriasis in 2018 from the Food and Drug Administration and the European Medicines Agency, have been published in the Lancet (2017 Jul 15;390[10091]:276-88).

Dr. Thaçi’s analysis of the 148-week outcomes was restricted to the patients who had at least a 75% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 75) at week 28. Nearly 80% of patients on tildrakizumab reached that threshold at week 28 in reSURFACE 1, as did 73% in reSURFACE 2.

The question asked in the extension study was, How do responders to tildrakizumab at 28 weeks fare after nearly 3 years on the drug? And the answer was: very well. Maintenance of at least a PASI 75 response was observed at 148 weeks in 91% of patients on tildrakizumab at the approved 100-mg dose and 92% of those on the 200-mg dose. The FDA-approved regimen is 100 mg by subcutaneous injection at weeks 0 and 4, and then every 12 weeks after that.

An intriguing feature of reSURFACE 1 was that a subset of PASI 75 responders at week 28 got taken off tildrakizumab at that point and switched to double-blind placebo, then restarted on their earlier dose of tildrakizumab upon relapse, which was defined as loss of at least 50% of the achieved on-drug PASI improvement.

At week 64, fully 48 weeks after their last dose of tildrakizumab, the relapse rate was 54% in the group formerly on 100 mg of tildrakizumab and slightly better at 47% in those formerly on 200 mg. The median time to relapse was 226 days in the 100-mg group and 258 days in the higher-dose arm. Those are exceptionally long times to relapse, and it’s useful information to file away in the event a psoriasis patient needs to discontinue biologic therapy for a period of time, Dr. Thaçi observed.

At week 64 – again, off active treatment since week 16 – 63% of the tildrakizumab 100-mg group had lost their previous PASI 75 response, as had 52% who were formerly on tildrakizumab at 200 mg.

The long-term safety profile of tildrakizumab paralleled that of placebo. For example, the exposure-adjusted adverse event rates of serious infections and major adverse cardiovascular events were closely similar in the placebo, tildrakizumab 100 mg, and tildrakizumab 200 mg groups.

There were two notable between-group differences in adverse events of interest: injection site reactions occurred at a rate of 5.36 per 100 person-years with placebo, compared with 1.94 and 2.3 per 100 person-years with tildrakizumab at 100 and 200 mg, respectively; and the incidence of nonmelanoma skin cancer was 0.97 cases per 100 person-years in the placebo arm, versus 0.5 and 0.49 cases per 100 person-years in the two tildrakizumab arms.

Dr. Thaçi did not present PASI 90 response outcomes because, at the time the reSURFACE trials were planned, PASI 75 was considered state of the art. The PASI 90 data are still being crunched but will be available soon. The 4- and 5-year follow-up data from the long-term extension studies are also on their way.

The reSURFACE 1 and reSURFACE 2 trials and their extension studies were funded by Sun Pharma and Merck. Dr. Thaçi reported receiving research grants from and serving as a consultant and paid scientific advisor to those pharmaceutical companies and more than a dozen others.

PARIS – Dermatologists are likely to do a double-take when they see the long-term efficacy and safety data for tildrakizumab (Ilumya), a high-affinity humanized monoclonal antibody targeting interleukin-23 p19, relative to the performance of older and more familiar biologic agents with other targets in psoriasis, Diamant Thaçi, MD, predicted at the annual congress of the European Academy of Dermatology and Venereology.

“The time to relapse [off tildrakizumab] is very different from what we are used to with other biologics; for example, the tumor necrosis factor inhibitors,” observed Dr. Thaçi, professor and chairman of the department of dermatology at the University of Lübeck (Germany).

He presented the 148-week, follow-up results of a pooled analysis of the open-label extension studies of reSURFACE 1 and reSURFACE 2, two pivotal phase 3 randomized double-blind international trials of 1,862 patients with moderate to severe chronic plaque psoriasis. The primary outcomes through week 12, which were instrumental in gaining marketing approval for tildrakizumab for treating psoriasis in 2018 from the Food and Drug Administration and the European Medicines Agency, have been published in the Lancet (2017 Jul 15;390[10091]:276-88).

Dr. Thaçi’s analysis of the 148-week outcomes was restricted to the patients who had at least a 75% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 75) at week 28. Nearly 80% of patients on tildrakizumab reached that threshold at week 28 in reSURFACE 1, as did 73% in reSURFACE 2.

The question asked in the extension study was, How do responders to tildrakizumab at 28 weeks fare after nearly 3 years on the drug? And the answer was: very well. Maintenance of at least a PASI 75 response was observed at 148 weeks in 91% of patients on tildrakizumab at the approved 100-mg dose and 92% of those on the 200-mg dose. The FDA-approved regimen is 100 mg by subcutaneous injection at weeks 0 and 4, and then every 12 weeks after that.

An intriguing feature of reSURFACE 1 was that a subset of PASI 75 responders at week 28 got taken off tildrakizumab at that point and switched to double-blind placebo, then restarted on their earlier dose of tildrakizumab upon relapse, which was defined as loss of at least 50% of the achieved on-drug PASI improvement.

At week 64, fully 48 weeks after their last dose of tildrakizumab, the relapse rate was 54% in the group formerly on 100 mg of tildrakizumab and slightly better at 47% in those formerly on 200 mg. The median time to relapse was 226 days in the 100-mg group and 258 days in the higher-dose arm. Those are exceptionally long times to relapse, and it’s useful information to file away in the event a psoriasis patient needs to discontinue biologic therapy for a period of time, Dr. Thaçi observed.

At week 64 – again, off active treatment since week 16 – 63% of the tildrakizumab 100-mg group had lost their previous PASI 75 response, as had 52% who were formerly on tildrakizumab at 200 mg.

The long-term safety profile of tildrakizumab paralleled that of placebo. For example, the exposure-adjusted adverse event rates of serious infections and major adverse cardiovascular events were closely similar in the placebo, tildrakizumab 100 mg, and tildrakizumab 200 mg groups.

There were two notable between-group differences in adverse events of interest: injection site reactions occurred at a rate of 5.36 per 100 person-years with placebo, compared with 1.94 and 2.3 per 100 person-years with tildrakizumab at 100 and 200 mg, respectively; and the incidence of nonmelanoma skin cancer was 0.97 cases per 100 person-years in the placebo arm, versus 0.5 and 0.49 cases per 100 person-years in the two tildrakizumab arms.

Dr. Thaçi did not present PASI 90 response outcomes because, at the time the reSURFACE trials were planned, PASI 75 was considered state of the art. The PASI 90 data are still being crunched but will be available soon. The 4- and 5-year follow-up data from the long-term extension studies are also on their way.

The reSURFACE 1 and reSURFACE 2 trials and their extension studies were funded by Sun Pharma and Merck. Dr. Thaçi reported receiving research grants from and serving as a consultant and paid scientific advisor to those pharmaceutical companies and more than a dozen others.

PARIS – Two-thirds of psoriasis patients with stable low disease activity while on full-dose biologic therapy can successfully undergo biologic dose reduction with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.

The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.

CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.

Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.


The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.

“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.

There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.

At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.

Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?

No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.

The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.

[email protected]

PARIS – Two-thirds of psoriasis patients with stable low disease activity while on full-dose biologic therapy can successfully undergo biologic dose reduction with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.

The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.

CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.

Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.


The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.

“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.

There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.

At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.

Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?

No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.

The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.

[email protected]

PARIS – Two-thirds of psoriasis patients with stable low disease activity while on full-dose biologic therapy can successfully undergo biologic dose reduction with long-term maintenance of disease control and no adverse consequences, Juul van den Reek, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

She presented the results of the CONDOR trial, the first-ever formal, randomized, controlled trial of tightly regulated dose reduction of biologics, compared with usual care standard-dose therapy. “Our current advice is we think you can try to reduce the dose because there are a lot of patients who benefit from this,” declared Dr. van den Reek, a dermatologist at Radboud University, Nijmegen, the Netherlands.

The advantages of this strategy are twofold: lower expenditures for this costly collection of medications and less exposure to any long-term, drug-related health risks, she noted.

CONDOR was a Dutch six-center, 12-month, open-label, unblinded, noninferiority, randomized trial including 111 patients. Participants had to have stable low disease activity as defined by both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores of 5 or less for at least 6 months while on standard-dose etanercept (Enbrel), adalimumab (Humira), or ustekinumab (Stelara) prior to enrollment. In fact, the average baseline PASI score was less than 2, with a DLQI of 0.

Participants were randomized to usual care – the customary approved dose of biologic therapy – or a drop down to 67% of that dose, achieved through prolongation of the dosing interval. If the reduced-dose patients kept their PASI and DLQI scores at 5 or less for 3 months straight, they dropped further to 50% of their original dose. However, patients who exceeded those thresholds were immediately returned to their previously effective dose.


The primary endpoint in this noninferiority trial was the difference in mean PASI scores between the dose-reduction and usual-care groups at 12 months. The prespecified margin for noninferiority was a difference of 0.5 PASI points. And that’s where the results get dicey: The mean difference turned out to be 1.1 PASI points in favor of usual care, meaning that, according to the study ground rules, dose reduction was not statistically noninferior. In hindsight, however, that 0.5-point margin was ill-considered and too narrowly defined.

“Within the chosen margins, the dose-reduction strategy seemed inferior. But what is the clinical relevance of a mean difference of 1.1 PASI points, when the accepted minimal clinically important difference is 3.2 points?” Dr. van den Reek observed.

There was no significant between-group difference in DLQI scores at 12 months. Nor did the two study arms differ in terms of the prespecified secondary endpoint of persistent disease flares as defined by a PASI or DLQI greater than 5 for 3 consecutive months: five patients in the reduced-dose group and three in the usual-care arm experienced such flares. There were no serious adverse events or other safety signals related to the intervention.

At 12 months, 50% of patients in the dose-reduction group were well maintained on 50% of their original approved-dose biologic and another 17% were doing well on 67% of their former dose.

Session chair Dedee Murrell, MD, professor of dermatology at the University of New South Wales, Sydney, noted that neither patients nor dermatologists were blinded as to treatment status in CONDOR. She then asked the question on everybody’s minds: Was there any loss of treatment efficacy when patients in the dose-reduction arm needed to resume higher-dose therapy?

No, Dr. van den Reek replied. She added that planned future CONDOR analyses include a cost-effectiveness determination as well as measurement of serum drug levels and identification of antidrug antibodies, information that might prove helpful in identifying an enriched population of patients most likely to respond favorably to biologic dose reduction. In addition, CONDOR-X, a long-term extension study, is ongoing in order to learn how patients on reduced-dose biologics fare after the 12-month mark.

The CONDOR trial was funded by the Netherlands Organization for Health Research and Development; Dr. van den Reek reported having no financial conflicts of interest.

[email protected]

A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.

The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.

Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.

Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.

The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.

The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.

By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.

The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.

Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.

“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.

These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.

Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.

SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.

A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.

The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.

Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.

Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.

The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.

The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.

By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.

The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.

Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.

“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.

These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.

Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.

SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.

A back pain screening questionnaire developed for ankylosing spondylitis performs well for identifying the subset of axial psoriatic arthritis patients who have active symptoms, according to researchers.

The inflammatory back pain criteria didn’t perform as well when patients with established disease but no symptoms were included, though using a lower cutoff point for the questionnaire improved its sensitivity, the researchers reported in the Annals of the Rheumatic Diseases.

Previous investigations showed that the inflammatory back pain criteria, as defined by the Assessment of Spondyloarthritis International Society (ASAS), had low sensitivity and high specificity for axial involvement in psoriatic arthritis.

Those earlier studies may have registered suboptimal performance of the inflammatory back pain criteria by not distinguishing between patients with axial disease in remission and those with active symptoms, according to Muhammad Haroon, PhD, of the division of rheumatology at University Hospital Kerry in Tralee, Ireland, and his coinvestigators.

The present study, which they said represents a much larger cohort than earlier investigations, included 406 patients with psoriatic arthritis, about one-quarter of whom had rheumatologist-diagnosed axial psoriatic arthritis. The mean age of the axial psoriatic arthritis patients was 51 years and 53% were male.

The researchers found that the inflammatory back pain criteria had poor sensitivity but good specificity at 59% and 84%, respectively, in patients with established axial psoriatic arthritis, defined as axial disease regardless of whether it was active or in remission.

By contrast, the criteria had good sensitivity and good specificity at 82% and 88%, respectively, in patients who had active axial psoriatic arthritis, according to the investigators.

The standard cutoff points used by the ASAS inflammatory back pain criteria may be too high for screening for early disease or for evaluating patients already receiving systemic therapies for psoriatic disease, the investigators said.

Looking at a lower cutoff point of three of five ASAS criteria, sensitivity was “quite high” for detecting established axial psoriatic arthritis, they said, increasing from 59% to 84%, while specificity remained relatively high, decreasing from 84% to 80%.

“We suggest that the standard cutoffs for this questionnaire be used for patients with active axial psoriatic arthritis, and the lower cutoffs should be used among patients with established axial psoriatic arthritis, where patients can potentially be in remission or partial remission,” they wrote in their report.

These findings could have important implications for the use of this screening tool in patients with psoriatic arthritis; however, more research is needed to validate the observations, the researchers cautioned.

Dr. Haroon reported competing interests related to AbbVie, Pfizer, and Celgene.

SOURCE: Haroon M et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214583.

Eli Lilly and Co. has announced positive results from the phase 3b/4, multicenter, randomized, open-label, parallel-group SPIRIT-H2H trial, which compared ixekizumab (Taltz) with adalimumab (Humira) in patients with psoriatic arthritis who had previously not taken a biologic disease-modifying antirheumatic drug.

The 52-week study included 566 patients with psoriatic arthritis. Patients received either ixekizumab at 80 mg every 4 weeks after a 160-mg loading dose or adalimumab at 40 mg every 2 weeks. The primary endpoint was the proportion of patients achieving at least a 50% reduction in American College of Rheumatology (ACR50) criteria at 24 weeks.

After 24 weeks, patients in the ixekizumab group were more likely to achieve ACR50, compared with those in the adalimumab group. In addition, patients receiving ixekizumab were more likely to achieve 100% skin clearance according to the Psoriasis Area and Severity Index. Ixekizumab also met all secondary trial endpoints.

“The positive results from the SPIRIT-H2H trial reinforce that Taltz effectively treats the debilitating joint signs and symptoms of active psoriatic arthritis, while also providing skin clearance. These results provide evidence that Taltz can be used as a first-line biologic treatment for patients with active psoriatic arthritis,” Lotus Mallbris, MD, PhD, vice president of immunology development at Lilly, said in the press release.

More detailed results will be presented at meetings and published in peer-reviewed journals in 2019, the company said.

[email protected]

Eli Lilly and Co. has announced positive results from the phase 3b/4, multicenter, randomized, open-label, parallel-group SPIRIT-H2H trial, which compared ixekizumab (Taltz) with adalimumab (Humira) in patients with psoriatic arthritis who had previously not taken a biologic disease-modifying antirheumatic drug.

The 52-week study included 566 patients with psoriatic arthritis. Patients received either ixekizumab at 80 mg every 4 weeks after a 160-mg loading dose or adalimumab at 40 mg every 2 weeks. The primary endpoint was the proportion of patients achieving at least a 50% reduction in American College of Rheumatology (ACR50) criteria at 24 weeks.

After 24 weeks, patients in the ixekizumab group were more likely to achieve ACR50, compared with those in the adalimumab group. In addition, patients receiving ixekizumab were more likely to achieve 100% skin clearance according to the Psoriasis Area and Severity Index. Ixekizumab also met all secondary trial endpoints.

“The positive results from the SPIRIT-H2H trial reinforce that Taltz effectively treats the debilitating joint signs and symptoms of active psoriatic arthritis, while also providing skin clearance. These results provide evidence that Taltz can be used as a first-line biologic treatment for patients with active psoriatic arthritis,” Lotus Mallbris, MD, PhD, vice president of immunology development at Lilly, said in the press release.

More detailed results will be presented at meetings and published in peer-reviewed journals in 2019, the company said.

[email protected]

Eli Lilly and Co. has announced positive results from the phase 3b/4, multicenter, randomized, open-label, parallel-group SPIRIT-H2H trial, which compared ixekizumab (Taltz) with adalimumab (Humira) in patients with psoriatic arthritis who had previously not taken a biologic disease-modifying antirheumatic drug.

The 52-week study included 566 patients with psoriatic arthritis. Patients received either ixekizumab at 80 mg every 4 weeks after a 160-mg loading dose or adalimumab at 40 mg every 2 weeks. The primary endpoint was the proportion of patients achieving at least a 50% reduction in American College of Rheumatology (ACR50) criteria at 24 weeks.

After 24 weeks, patients in the ixekizumab group were more likely to achieve ACR50, compared with those in the adalimumab group. In addition, patients receiving ixekizumab were more likely to achieve 100% skin clearance according to the Psoriasis Area and Severity Index. Ixekizumab also met all secondary trial endpoints.

“The positive results from the SPIRIT-H2H trial reinforce that Taltz effectively treats the debilitating joint signs and symptoms of active psoriatic arthritis, while also providing skin clearance. These results provide evidence that Taltz can be used as a first-line biologic treatment for patients with active psoriatic arthritis,” Lotus Mallbris, MD, PhD, vice president of immunology development at Lilly, said in the press release.

More detailed results will be presented at meetings and published in peer-reviewed journals in 2019, the company said.

[email protected]

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

The American College of Rheumatology and the National Psoriasis Foundation have released a joint treatment guideline for psoriatic arthritis that, for the first time, includes a conditional recommendation to use tumor necrosis factor–inhibitor(TNFi) biologics over methotrexate and other oral small molecules as a first-line therapy in patients with active disease.

“The available low-quality evidence is inconclusive regarding the efficacy of OSMs [oral small molecules] in management of PsA, whereas there is moderate-quality evidence of the benefits of TNFi biologics, in particular regarding their impact on the prevention of disease progression and joint damage,” wrote the panel of authors, who were led by Jasvinder A. Singh, MD, of the University of Alabama at Birmingham. “In making their recommendation, the panel recognized the cost implications, but put considerations of quality of evidence for benefit over other considerations. This guideline provides recommendations for early and aggressive therapy in patients with newly diagnosed PsA.”

The 28-page guideline, published online Nov. 30 in the Journal of Psoriasis and Psoriatic Arthritis and also in Arthritis Care & Research and Arthritis & Rheumatology, is the first set of PsA-specific recommendations to be assembled using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology that the ACR has used for RA and other conditions. GRADE uses systematic reviews of the scientific literature available to evaluate and grade the quality of evidence in a particular domain. The evidence reviews are then used to create guideline recommendations for or against particular therapy options that range from strong to conditional, depending on the quality of evidence available.

Based on the GRADE methodology and consensus building, the guideline authors crafted recommendations for eight different clinical scenarios, including the initial treatment of patients with active PsA who have not received either OSMs or other treatments; treatment of patients with active PsA despite treatment with an OSM; treatment of patients with active PsA despite treatment with a TNFi biologic either as monotherapy or in combination with methotrexate; treatment of patients with active PsA despite treatment with an interleukin (IL)-17 inhibitor or IL-12/23 inhibitor monotherapy; treatment of patients with active PsA including treat-to-target, active axial disease, enthesitis, or active inflammatory bowel disease; treatment of patients with active PsA and comorbidities, including concomitant diabetes and recurrent serious infections; vaccination in patients with active PsA; and treatment of patients with active PsA with nonpharmacologic interventions such as yoga and weight loss. Most of the treatment recommendations are conditional based on very low to moderate quality evidence. “Health care providers and patients must take into consideration all active disease domains, comorbidities, and the patient’s functional status in choosing the optimal therapy for an individual at a given point in time,” the authors emphasized.

Only five of the recommendations are listed as strong, including smoking cessation. Three of the strong recommendations concern adult patients with active PsA and concomitant active inflammatory bowel disease despite treatment with an OSM. They are “switch to a monoclonal antibody TNFi biologic over a TNFi biologic soluble receptor biologic,” “switch to a TNFi monoclonal antibody biologic over an IL-7i biologic,” and “switch to an IL-12/23i biologic over switching to an IL-17i biologic.”

The process of creating the guideline included input from a panel of nine adults who provided the authors with perspective on their values and preferences. “The concept of treat-to-target was challenging for patients,” the authors noted. “Although they saw value in improved outcomes, they also thought this strategy could increase costs to the patient (e.g., copayments, time traveling to more frequent appointments, etc.) and potentially increase adverse events. Therefore, a detailed conversation with the patient is needed to make decisions regarding treat-to-target.”

The authors concluded the guideline by calling for more comparative data to inform treatment selection in the future. “Several ongoing trials, including a trial to compare a TNFi biologic combination therapy with a TNFi biologic monotherapy and MTX monotherapy, will inform treatment decisions,” they wrote. “We anticipate future updates to the guideline when new evidence is available.”

Dr. Singh, who is also a staff rheumatologist at the Birmingham (Ala.) Veterans Affairs Medical Center, led development of the 2012 and 2015 ACR treatment guidelines for RA. He has received consulting fees from a variety of companies marketing rheumatologic drugs as well as research support from Takeda and Savient. The other guideline authors reported having numerous financial ties to industry.

[email protected]

SOURCE: Singh J et al. Arthritis Care Res. 2018 Nov 30. doi: 10.1002/acr.23789.

The American College of Rheumatology and the National Psoriasis Foundation have released a joint treatment guideline for psoriatic arthritis that, for the first time, includes a conditional recommendation to use tumor necrosis factor–inhibitor(TNFi) biologics over methotrexate and other oral small molecules as a first-line therapy in patients with active disease.

“The available low-quality evidence is inconclusive regarding the efficacy of OSMs [oral small molecules] in management of PsA, whereas there is moderate-quality evidence of the benefits of TNFi biologics, in particular regarding their impact on the prevention of disease progression and joint damage,” wrote the panel of authors, who were led by Jasvinder A. Singh, MD, of the University of Alabama at Birmingham. “In making their recommendation, the panel recognized the cost implications, but put considerations of quality of evidence for benefit over other considerations. This guideline provides recommendations for early and aggressive therapy in patients with newly diagnosed PsA.”

The 28-page guideline, published online Nov. 30 in the Journal of Psoriasis and Psoriatic Arthritis and also in Arthritis Care & Research and Arthritis & Rheumatology, is the first set of PsA-specific recommendations to be assembled using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology that the ACR has used for RA and other conditions. GRADE uses systematic reviews of the scientific literature available to evaluate and grade the quality of evidence in a particular domain. The evidence reviews are then used to create guideline recommendations for or against particular therapy options that range from strong to conditional, depending on the quality of evidence available.

Based on the GRADE methodology and consensus building, the guideline authors crafted recommendations for eight different clinical scenarios, including the initial treatment of patients with active PsA who have not received either OSMs or other treatments; treatment of patients with active PsA despite treatment with an OSM; treatment of patients with active PsA despite treatment with a TNFi biologic either as monotherapy or in combination with methotrexate; treatment of patients with active PsA despite treatment with an interleukin (IL)-17 inhibitor or IL-12/23 inhibitor monotherapy; treatment of patients with active PsA including treat-to-target, active axial disease, enthesitis, or active inflammatory bowel disease; treatment of patients with active PsA and comorbidities, including concomitant diabetes and recurrent serious infections; vaccination in patients with active PsA; and treatment of patients with active PsA with nonpharmacologic interventions such as yoga and weight loss. Most of the treatment recommendations are conditional based on very low to moderate quality evidence. “Health care providers and patients must take into consideration all active disease domains, comorbidities, and the patient’s functional status in choosing the optimal therapy for an individual at a given point in time,” the authors emphasized.

Only five of the recommendations are listed as strong, including smoking cessation. Three of the strong recommendations concern adult patients with active PsA and concomitant active inflammatory bowel disease despite treatment with an OSM. They are “switch to a monoclonal antibody TNFi biologic over a TNFi biologic soluble receptor biologic,” “switch to a TNFi monoclonal antibody biologic over an IL-7i biologic,” and “switch to an IL-12/23i biologic over switching to an IL-17i biologic.”

The process of creating the guideline included input from a panel of nine adults who provided the authors with perspective on their values and preferences. “The concept of treat-to-target was challenging for patients,” the authors noted. “Although they saw value in improved outcomes, they also thought this strategy could increase costs to the patient (e.g., copayments, time traveling to more frequent appointments, etc.) and potentially increase adverse events. Therefore, a detailed conversation with the patient is needed to make decisions regarding treat-to-target.”

The authors concluded the guideline by calling for more comparative data to inform treatment selection in the future. “Several ongoing trials, including a trial to compare a TNFi biologic combination therapy with a TNFi biologic monotherapy and MTX monotherapy, will inform treatment decisions,” they wrote. “We anticipate future updates to the guideline when new evidence is available.”

Dr. Singh, who is also a staff rheumatologist at the Birmingham (Ala.) Veterans Affairs Medical Center, led development of the 2012 and 2015 ACR treatment guidelines for RA. He has received consulting fees from a variety of companies marketing rheumatologic drugs as well as research support from Takeda and Savient. The other guideline authors reported having numerous financial ties to industry.

[email protected]

SOURCE: Singh J et al. Arthritis Care Res. 2018 Nov 30. doi: 10.1002/acr.23789.

The American College of Rheumatology and the National Psoriasis Foundation have released a joint treatment guideline for psoriatic arthritis that, for the first time, includes a conditional recommendation to use tumor necrosis factor–inhibitor(TNFi) biologics over methotrexate and other oral small molecules as a first-line therapy in patients with active disease.

“The available low-quality evidence is inconclusive regarding the efficacy of OSMs [oral small molecules] in management of PsA, whereas there is moderate-quality evidence of the benefits of TNFi biologics, in particular regarding their impact on the prevention of disease progression and joint damage,” wrote the panel of authors, who were led by Jasvinder A. Singh, MD, of the University of Alabama at Birmingham. “In making their recommendation, the panel recognized the cost implications, but put considerations of quality of evidence for benefit over other considerations. This guideline provides recommendations for early and aggressive therapy in patients with newly diagnosed PsA.”

The 28-page guideline, published online Nov. 30 in the Journal of Psoriasis and Psoriatic Arthritis and also in Arthritis Care & Research and Arthritis & Rheumatology, is the first set of PsA-specific recommendations to be assembled using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology that the ACR has used for RA and other conditions. GRADE uses systematic reviews of the scientific literature available to evaluate and grade the quality of evidence in a particular domain. The evidence reviews are then used to create guideline recommendations for or against particular therapy options that range from strong to conditional, depending on the quality of evidence available.

Based on the GRADE methodology and consensus building, the guideline authors crafted recommendations for eight different clinical scenarios, including the initial treatment of patients with active PsA who have not received either OSMs or other treatments; treatment of patients with active PsA despite treatment with an OSM; treatment of patients with active PsA despite treatment with a TNFi biologic either as monotherapy or in combination with methotrexate; treatment of patients with active PsA despite treatment with an interleukin (IL)-17 inhibitor or IL-12/23 inhibitor monotherapy; treatment of patients with active PsA including treat-to-target, active axial disease, enthesitis, or active inflammatory bowel disease; treatment of patients with active PsA and comorbidities, including concomitant diabetes and recurrent serious infections; vaccination in patients with active PsA; and treatment of patients with active PsA with nonpharmacologic interventions such as yoga and weight loss. Most of the treatment recommendations are conditional based on very low to moderate quality evidence. “Health care providers and patients must take into consideration all active disease domains, comorbidities, and the patient’s functional status in choosing the optimal therapy for an individual at a given point in time,” the authors emphasized.

Only five of the recommendations are listed as strong, including smoking cessation. Three of the strong recommendations concern adult patients with active PsA and concomitant active inflammatory bowel disease despite treatment with an OSM. They are “switch to a monoclonal antibody TNFi biologic over a TNFi biologic soluble receptor biologic,” “switch to a TNFi monoclonal antibody biologic over an IL-7i biologic,” and “switch to an IL-12/23i biologic over switching to an IL-17i biologic.”

The process of creating the guideline included input from a panel of nine adults who provided the authors with perspective on their values and preferences. “The concept of treat-to-target was challenging for patients,” the authors noted. “Although they saw value in improved outcomes, they also thought this strategy could increase costs to the patient (e.g., copayments, time traveling to more frequent appointments, etc.) and potentially increase adverse events. Therefore, a detailed conversation with the patient is needed to make decisions regarding treat-to-target.”

The authors concluded the guideline by calling for more comparative data to inform treatment selection in the future. “Several ongoing trials, including a trial to compare a TNFi biologic combination therapy with a TNFi biologic monotherapy and MTX monotherapy, will inform treatment decisions,” they wrote. “We anticipate future updates to the guideline when new evidence is available.”

Dr. Singh, who is also a staff rheumatologist at the Birmingham (Ala.) Veterans Affairs Medical Center, led development of the 2012 and 2015 ACR treatment guidelines for RA. He has received consulting fees from a variety of companies marketing rheumatologic drugs as well as research support from Takeda and Savient. The other guideline authors reported having numerous financial ties to industry.

[email protected]

SOURCE: Singh J et al. Arthritis Care Res. 2018 Nov 30. doi: 10.1002/acr.23789.

CHICAGO – The selective Janus kinase 1 inhibitor filgotinib showed efficacy and safety for patients with rheumatoid arthritis in a phase 3 trial, and efficacy and safety for treating patients with psoriatic arthritis in results from a phase 2 study in two separate reports at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/MDedge News

In the phase 3 study, treatment with filgotinib at an oral dosage of 200 mg once daily led to a 66% incidence of American College of Rheumatology 20 (ACR20) responses after 16 weeks of treatment in 147 patients with moderately to severely active rheumatoid arthritis (RA), compared with a 31% rate among 148 patients randomized to receive placebo, a statistically significant improvement for the study’s primary efficacy endpoint, Mark C. Genovese, MD, reported in a poster at the meeting. The rate of ACR20 responses among the 153 RA patients who received 100 mg/day filgotinib was 58%, reported Dr. Genovese, professor of medicine and director of the rheumatology clinic at Stanford (Calif.) University.

After 24 weeks of daily treatment, the longest duration studied in the trial, ACR20 rates were 69%, 55%, and 35% in the 200-mg, 100-mg, and placebo patients, respectively. Dr. Genovese also reported that after 24 weeks on treatment, the rates of patients achieving low disease activity measured by their disease activity score based on 28 joints and C-reactive protein level (DAS28-CRP) were 48%, 38%, and 21%, respectively, and the percentages of patients achieving complete remission at 24 weeks based on their DAS28-CRP scores were 31%, 26%, and 12%, respectively.

“We were incredibly fortunate to see such positive results. The drug worked very well in very-challenging-to-treat patients,” Dr. Genovese said in an interview. All of the RA patients enrolled in the study had not previously responded to or were intolerant of prior treatment with at least one biologic disease-modifying antirheumatic drug (DMARD), and almost a quarter of enrolled patients had failed prior treatment with at least three different biologic DMARDs. The number of biologic DMARDs a patient had previously received showed no relationship to how well patients responded to filgotinib, he noted.

Dr. Genovese also highlighted the relatively high percentage of patients who achieved low disease activity and remission. The 48% and 31% rates, respectively, of low disease activity and remission among patients treated with the higher filgotinib dosage for 24 weeks “is fairly impressive in patients who did not previously respond to a biologic DMARD,” the researcher said. These findings are similar to data previously reported for upadacitinib, another Janus kinase (JAK) inhibitor that, like filgotinib, is selective for the JAK1 receptor, noted Dr. Genovese, who also was the lead investigator for a phase 3 study of upadacitinib in RA patients (Lancet. 2018 June 23;391[10139]:2513-24).

The filgotinib data he presented came from the FINCH 2 (Filgotinib Versus Placebo in Adults With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic Disease-Modifying Anti-Rheumatic Drug[s] Treatment) trial, which was run at 104 sites in 15 countries, including the United States. The results also showed a “favorable safety profile and stable laboratory parameters,” Dr. Genovese reported. Results from two additional phase 3 trials in RA patients are expected in 2019, he said.

Filgotinib studied in psoriatic arthritis

The separate, phase 2 study of filgotinib in patients with psoriatic arthritis (PsA) reported during the meeting showed safety “in line with previous reports without new safety signals” in a multicenter trial with 131 patients randomized to receive oral filgotinib 200 mg daily for 16 weeks or placebo, Philip J. Mease, MD, reported in a talk at the meeting. For the primary endpoint of achievement of ACR20 response after 16 weeks, the rate was 80% of the filgotinib-treated patients and 33% of patients in the placebo group, a statistically significant difference, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.

Mitchel L. Zoler/MDedge News

EQUATOR (A Study to Assess Efficacy and Safety of Filgotinib in Active Psoriatic Arthritis) enrolled patients at sites in seven European countries who had “very active” PsA and either a history of or current plaque psoriasis. All patients had to have a history of either insufficient response to or intolerance of at least one conventional synthetic DMARD. The enrollment criteria had no specifications for prior use of an anti–tumor necrosis factor drug, and about 15% of patients had used least one of these drugs. At entry, about three-quarters of patients were on treatment with a conventional synthetic DMARD and about a quarter received treatment with a glucocorticoid.

The results showed statistically significant benefits from filgotinib, compared with placebo, for several other measures of arthritis activity, as well as measures of psoriasis, enthesitis, and pain, Dr. Mease reported. He also highlighted a “lack of meaningful changes in hemoglobin” or other laboratory measures that, along with the efficacy findings, make filgotinib “a promising first step” for patients with PsA. Dr. Mease also noted that roughly concurrently with his report, a separate group of researchers published results from a phase 2 study of filgotinib in patients with ankylosing spondylitis that also found evidence for efficacy and safety during 12 weeks of treating 116 randomized patients (Lancet. 2018 Oct 22. doi: 10.1016/S0140-6736[18]32463-2).

FINCH 2 was sponsored by Galapagos and Gilead, the two companies developing filgotinib. Dr. Genovese has had financial relationships with Galapagos and Gilead and also with AbbVie, Lilly, and Pfizer. Dr. Mease has had financial relationships with Galapagos and Gilead and a dozen other companies.

[email protected]

SOURCES: Genovese M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L06; Mease P et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1821.

CHICAGO – The selective Janus kinase 1 inhibitor filgotinib showed efficacy and safety for patients with rheumatoid arthritis in a phase 3 trial, and efficacy and safety for treating patients with psoriatic arthritis in results from a phase 2 study in two separate reports at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/MDedge News

In the phase 3 study, treatment with filgotinib at an oral dosage of 200 mg once daily led to a 66% incidence of American College of Rheumatology 20 (ACR20) responses after 16 weeks of treatment in 147 patients with moderately to severely active rheumatoid arthritis (RA), compared with a 31% rate among 148 patients randomized to receive placebo, a statistically significant improvement for the study’s primary efficacy endpoint, Mark C. Genovese, MD, reported in a poster at the meeting. The rate of ACR20 responses among the 153 RA patients who received 100 mg/day filgotinib was 58%, reported Dr. Genovese, professor of medicine and director of the rheumatology clinic at Stanford (Calif.) University.

After 24 weeks of daily treatment, the longest duration studied in the trial, ACR20 rates were 69%, 55%, and 35% in the 200-mg, 100-mg, and placebo patients, respectively. Dr. Genovese also reported that after 24 weeks on treatment, the rates of patients achieving low disease activity measured by their disease activity score based on 28 joints and C-reactive protein level (DAS28-CRP) were 48%, 38%, and 21%, respectively, and the percentages of patients achieving complete remission at 24 weeks based on their DAS28-CRP scores were 31%, 26%, and 12%, respectively.

“We were incredibly fortunate to see such positive results. The drug worked very well in very-challenging-to-treat patients,” Dr. Genovese said in an interview. All of the RA patients enrolled in the study had not previously responded to or were intolerant of prior treatment with at least one biologic disease-modifying antirheumatic drug (DMARD), and almost a quarter of enrolled patients had failed prior treatment with at least three different biologic DMARDs. The number of biologic DMARDs a patient had previously received showed no relationship to how well patients responded to filgotinib, he noted.

Dr. Genovese also highlighted the relatively high percentage of patients who achieved low disease activity and remission. The 48% and 31% rates, respectively, of low disease activity and remission among patients treated with the higher filgotinib dosage for 24 weeks “is fairly impressive in patients who did not previously respond to a biologic DMARD,” the researcher said. These findings are similar to data previously reported for upadacitinib, another Janus kinase (JAK) inhibitor that, like filgotinib, is selective for the JAK1 receptor, noted Dr. Genovese, who also was the lead investigator for a phase 3 study of upadacitinib in RA patients (Lancet. 2018 June 23;391[10139]:2513-24).

The filgotinib data he presented came from the FINCH 2 (Filgotinib Versus Placebo in Adults With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic Disease-Modifying Anti-Rheumatic Drug[s] Treatment) trial, which was run at 104 sites in 15 countries, including the United States. The results also showed a “favorable safety profile and stable laboratory parameters,” Dr. Genovese reported. Results from two additional phase 3 trials in RA patients are expected in 2019, he said.

Filgotinib studied in psoriatic arthritis

The separate, phase 2 study of filgotinib in patients with psoriatic arthritis (PsA) reported during the meeting showed safety “in line with previous reports without new safety signals” in a multicenter trial with 131 patients randomized to receive oral filgotinib 200 mg daily for 16 weeks or placebo, Philip J. Mease, MD, reported in a talk at the meeting. For the primary endpoint of achievement of ACR20 response after 16 weeks, the rate was 80% of the filgotinib-treated patients and 33% of patients in the placebo group, a statistically significant difference, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.

Mitchel L. Zoler/MDedge News

EQUATOR (A Study to Assess Efficacy and Safety of Filgotinib in Active Psoriatic Arthritis) enrolled patients at sites in seven European countries who had “very active” PsA and either a history of or current plaque psoriasis. All patients had to have a history of either insufficient response to or intolerance of at least one conventional synthetic DMARD. The enrollment criteria had no specifications for prior use of an anti–tumor necrosis factor drug, and about 15% of patients had used least one of these drugs. At entry, about three-quarters of patients were on treatment with a conventional synthetic DMARD and about a quarter received treatment with a glucocorticoid.

The results showed statistically significant benefits from filgotinib, compared with placebo, for several other measures of arthritis activity, as well as measures of psoriasis, enthesitis, and pain, Dr. Mease reported. He also highlighted a “lack of meaningful changes in hemoglobin” or other laboratory measures that, along with the efficacy findings, make filgotinib “a promising first step” for patients with PsA. Dr. Mease also noted that roughly concurrently with his report, a separate group of researchers published results from a phase 2 study of filgotinib in patients with ankylosing spondylitis that also found evidence for efficacy and safety during 12 weeks of treating 116 randomized patients (Lancet. 2018 Oct 22. doi: 10.1016/S0140-6736[18]32463-2).

FINCH 2 was sponsored by Galapagos and Gilead, the two companies developing filgotinib. Dr. Genovese has had financial relationships with Galapagos and Gilead and also with AbbVie, Lilly, and Pfizer. Dr. Mease has had financial relationships with Galapagos and Gilead and a dozen other companies.

[email protected]

SOURCES: Genovese M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L06; Mease P et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1821.

CHICAGO – The selective Janus kinase 1 inhibitor filgotinib showed efficacy and safety for patients with rheumatoid arthritis in a phase 3 trial, and efficacy and safety for treating patients with psoriatic arthritis in results from a phase 2 study in two separate reports at the annual meeting of the American College of Rheumatology.

Mitchel L. Zoler/MDedge News

In the phase 3 study, treatment with filgotinib at an oral dosage of 200 mg once daily led to a 66% incidence of American College of Rheumatology 20 (ACR20) responses after 16 weeks of treatment in 147 patients with moderately to severely active rheumatoid arthritis (RA), compared with a 31% rate among 148 patients randomized to receive placebo, a statistically significant improvement for the study’s primary efficacy endpoint, Mark C. Genovese, MD, reported in a poster at the meeting. The rate of ACR20 responses among the 153 RA patients who received 100 mg/day filgotinib was 58%, reported Dr. Genovese, professor of medicine and director of the rheumatology clinic at Stanford (Calif.) University.

After 24 weeks of daily treatment, the longest duration studied in the trial, ACR20 rates were 69%, 55%, and 35% in the 200-mg, 100-mg, and placebo patients, respectively. Dr. Genovese also reported that after 24 weeks on treatment, the rates of patients achieving low disease activity measured by their disease activity score based on 28 joints and C-reactive protein level (DAS28-CRP) were 48%, 38%, and 21%, respectively, and the percentages of patients achieving complete remission at 24 weeks based on their DAS28-CRP scores were 31%, 26%, and 12%, respectively.

“We were incredibly fortunate to see such positive results. The drug worked very well in very-challenging-to-treat patients,” Dr. Genovese said in an interview. All of the RA patients enrolled in the study had not previously responded to or were intolerant of prior treatment with at least one biologic disease-modifying antirheumatic drug (DMARD), and almost a quarter of enrolled patients had failed prior treatment with at least three different biologic DMARDs. The number of biologic DMARDs a patient had previously received showed no relationship to how well patients responded to filgotinib, he noted.

Dr. Genovese also highlighted the relatively high percentage of patients who achieved low disease activity and remission. The 48% and 31% rates, respectively, of low disease activity and remission among patients treated with the higher filgotinib dosage for 24 weeks “is fairly impressive in patients who did not previously respond to a biologic DMARD,” the researcher said. These findings are similar to data previously reported for upadacitinib, another Janus kinase (JAK) inhibitor that, like filgotinib, is selective for the JAK1 receptor, noted Dr. Genovese, who also was the lead investigator for a phase 3 study of upadacitinib in RA patients (Lancet. 2018 June 23;391[10139]:2513-24).

The filgotinib data he presented came from the FINCH 2 (Filgotinib Versus Placebo in Adults With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic Disease-Modifying Anti-Rheumatic Drug[s] Treatment) trial, which was run at 104 sites in 15 countries, including the United States. The results also showed a “favorable safety profile and stable laboratory parameters,” Dr. Genovese reported. Results from two additional phase 3 trials in RA patients are expected in 2019, he said.

Filgotinib studied in psoriatic arthritis

The separate, phase 2 study of filgotinib in patients with psoriatic arthritis (PsA) reported during the meeting showed safety “in line with previous reports without new safety signals” in a multicenter trial with 131 patients randomized to receive oral filgotinib 200 mg daily for 16 weeks or placebo, Philip J. Mease, MD, reported in a talk at the meeting. For the primary endpoint of achievement of ACR20 response after 16 weeks, the rate was 80% of the filgotinib-treated patients and 33% of patients in the placebo group, a statistically significant difference, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.

Mitchel L. Zoler/MDedge News

EQUATOR (A Study to Assess Efficacy and Safety of Filgotinib in Active Psoriatic Arthritis) enrolled patients at sites in seven European countries who had “very active” PsA and either a history of or current plaque psoriasis. All patients had to have a history of either insufficient response to or intolerance of at least one conventional synthetic DMARD. The enrollment criteria had no specifications for prior use of an anti–tumor necrosis factor drug, and about 15% of patients had used least one of these drugs. At entry, about three-quarters of patients were on treatment with a conventional synthetic DMARD and about a quarter received treatment with a glucocorticoid.

The results showed statistically significant benefits from filgotinib, compared with placebo, for several other measures of arthritis activity, as well as measures of psoriasis, enthesitis, and pain, Dr. Mease reported. He also highlighted a “lack of meaningful changes in hemoglobin” or other laboratory measures that, along with the efficacy findings, make filgotinib “a promising first step” for patients with PsA. Dr. Mease also noted that roughly concurrently with his report, a separate group of researchers published results from a phase 2 study of filgotinib in patients with ankylosing spondylitis that also found evidence for efficacy and safety during 12 weeks of treating 116 randomized patients (Lancet. 2018 Oct 22. doi: 10.1016/S0140-6736[18]32463-2).

FINCH 2 was sponsored by Galapagos and Gilead, the two companies developing filgotinib. Dr. Genovese has had financial relationships with Galapagos and Gilead and also with AbbVie, Lilly, and Pfizer. Dr. Mease has had financial relationships with Galapagos and Gilead and a dozen other companies.

[email protected]

SOURCES: Genovese M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L06; Mease P et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1821.

CHICAGO – Overweight and obese psoriasis patients have it within their power to reduce their risk of developing psoriatic arthritis through weight loss, according to a large British longitudinal study.

Bruce Jancin/MDedge News

Of the three modifiable lifestyle factors evaluated in the study as potential risk factors for the development of psoriatic arthritis in psoriasis patients – body mass index, smoking, and alcohol intake – reduction in BMI over time was clearly the winning strategy, Neil McHugh, MD, said at the annual meeting of the American College of Rheumatology.

The message from this study of 90,189 incident cases of psoriasis identified in the U.K. Clinical Practice Research Datalink was unequivocal: “If you’re overweight and have psoriasis and you lose weight, you reduce your chance of developing a nasty form of arthritis,” said Dr. McHugh, professor of pharmacoepidemiology and a rheumatologist at the University of Bath, England.

“As psoriatic arthritis affects around 20% of people with psoriasis, weight reduction amongst those who are obese may have the potential to greatly reduce their risk of psoriatic arthritis in addition to providing additional health benefits,” he added.

Among the more than 90,000 patients diagnosed with psoriasis, 1,409 subsequently developed psoriatic arthritis, with an overall incidence rate of 2.72 cases per 1,000 person-years. Baseline BMI was strongly associated in stepwise fashion with subsequent psoriatic arthritis. Psoriasis patients with a baseline BMI of 25-29.9 kg/m² were at an adjusted 1.76-fold increased risk of later developing psoriatic arthritis, compared with psoriasis patients having a BMI of less than 25. For those with a BMI of 30-34.9 kg/m², the risk of subsequent psoriatic arthritis was increased 2.04-fold. And for those with a baseline BMI of 35 kg/m² or more, the risk was increased 2.42-fold in analyses adjusted for age, sex, psoriasis duration and severity, history of trauma, and diabetes.

In contrast, the risk of developing psoriatic arthritis wasn’t significantly different between psoriasis patients who were nonsmokers, ex-smokers, or current smokers. And while there was a significantly increased risk of developing psoriatic arthritis in psoriasis patients who were current drinkers, compared with nondrinkers, the risk in ex-drinkers and heavy drinkers was similar to that in nondrinkers, a counterintuitive finding Dr. McHugh suspects was a distortion due to small numbers.

While the observed relationship between baseline BMI and subsequent risk of psoriatic arthritis was informative, it only tells part of the story, since body weight so often changes over time. Dr. McHugh and his coinvestigators had data on change in BMI over the course of 10 years of follow-up in 15,627 psoriasis patients free of psoriatic arthritis at the time their psoriasis was diagnosed. The researchers developed a BMI risk calculator that expressed the effect of change in BMI over time on the cumulative risk of developing psoriatic arthritis.

“We were able to show that if, for instance, you started with a BMI of 25 at baseline and ended up with a BMI of 30, your risk of psoriatic arthritis goes up by 13%, whereas if you start at 30 and come down to 25, your risk decreases by 13%. And the more weight you lose, the greater you reduce your risk of developing psoriatic arthritis,” the rheumatologist explained in an interview.

Indeed, with more extreme changes in BMI over the course of a decade following diagnosis of psoriasis – for example, dropping from a baseline BMI of 36 kg/m² to 23 kg/m² – the risk of developing psoriatic arthritis fell by close to 30%.

Dr. McHugh reported having no financial conflicts regarding this study, funded by the U.K. National Institute for Health Research.

[email protected]

SOURCE: Green A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2134.

CHICAGO – Overweight and obese psoriasis patients have it within their power to reduce their risk of developing psoriatic arthritis through weight loss, according to a large British longitudinal study.

Bruce Jancin/MDedge News

Of the three modifiable lifestyle factors evaluated in the study as potential risk factors for the development of psoriatic arthritis in psoriasis patients – body mass index, smoking, and alcohol intake – reduction in BMI over time was clearly the winning strategy, Neil McHugh, MD, said at the annual meeting of the American College of Rheumatology.

The message from this study of 90,189 incident cases of psoriasis identified in the U.K. Clinical Practice Research Datalink was unequivocal: “If you’re overweight and have psoriasis and you lose weight, you reduce your chance of developing a nasty form of arthritis,” said Dr. McHugh, professor of pharmacoepidemiology and a rheumatologist at the University of Bath, England.

“As psoriatic arthritis affects around 20% of people with psoriasis, weight reduction amongst those who are obese may have the potential to greatly reduce their risk of psoriatic arthritis in addition to providing additional health benefits,” he added.

Among the more than 90,000 patients diagnosed with psoriasis, 1,409 subsequently developed psoriatic arthritis, with an overall incidence rate of 2.72 cases per 1,000 person-years. Baseline BMI was strongly associated in stepwise fashion with subsequent psoriatic arthritis. Psoriasis patients with a baseline BMI of 25-29.9 kg/m² were at an adjusted 1.76-fold increased risk of later developing psoriatic arthritis, compared with psoriasis patients having a BMI of less than 25. For those with a BMI of 30-34.9 kg/m², the risk of subsequent psoriatic arthritis was increased 2.04-fold. And for those with a baseline BMI of 35 kg/m² or more, the risk was increased 2.42-fold in analyses adjusted for age, sex, psoriasis duration and severity, history of trauma, and diabetes.

In contrast, the risk of developing psoriatic arthritis wasn’t significantly different between psoriasis patients who were nonsmokers, ex-smokers, or current smokers. And while there was a significantly increased risk of developing psoriatic arthritis in psoriasis patients who were current drinkers, compared with nondrinkers, the risk in ex-drinkers and heavy drinkers was similar to that in nondrinkers, a counterintuitive finding Dr. McHugh suspects was a distortion due to small numbers.

While the observed relationship between baseline BMI and subsequent risk of psoriatic arthritis was informative, it only tells part of the story, since body weight so often changes over time. Dr. McHugh and his coinvestigators had data on change in BMI over the course of 10 years of follow-up in 15,627 psoriasis patients free of psoriatic arthritis at the time their psoriasis was diagnosed. The researchers developed a BMI risk calculator that expressed the effect of change in BMI over time on the cumulative risk of developing psoriatic arthritis.

“We were able to show that if, for instance, you started with a BMI of 25 at baseline and ended up with a BMI of 30, your risk of psoriatic arthritis goes up by 13%, whereas if you start at 30 and come down to 25, your risk decreases by 13%. And the more weight you lose, the greater you reduce your risk of developing psoriatic arthritis,” the rheumatologist explained in an interview.

Indeed, with more extreme changes in BMI over the course of a decade following diagnosis of psoriasis – for example, dropping from a baseline BMI of 36 kg/m² to 23 kg/m² – the risk of developing psoriatic arthritis fell by close to 30%.

Dr. McHugh reported having no financial conflicts regarding this study, funded by the U.K. National Institute for Health Research.

[email protected]

SOURCE: Green A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2134.

CHICAGO – Overweight and obese psoriasis patients have it within their power to reduce their risk of developing psoriatic arthritis through weight loss, according to a large British longitudinal study.

Bruce Jancin/MDedge News

Of the three modifiable lifestyle factors evaluated in the study as potential risk factors for the development of psoriatic arthritis in psoriasis patients – body mass index, smoking, and alcohol intake – reduction in BMI over time was clearly the winning strategy, Neil McHugh, MD, said at the annual meeting of the American College of Rheumatology.

The message from this study of 90,189 incident cases of psoriasis identified in the U.K. Clinical Practice Research Datalink was unequivocal: “If you’re overweight and have psoriasis and you lose weight, you reduce your chance of developing a nasty form of arthritis,” said Dr. McHugh, professor of pharmacoepidemiology and a rheumatologist at the University of Bath, England.

“As psoriatic arthritis affects around 20% of people with psoriasis, weight reduction amongst those who are obese may have the potential to greatly reduce their risk of psoriatic arthritis in addition to providing additional health benefits,” he added.

Among the more than 90,000 patients diagnosed with psoriasis, 1,409 subsequently developed psoriatic arthritis, with an overall incidence rate of 2.72 cases per 1,000 person-years. Baseline BMI was strongly associated in stepwise fashion with subsequent psoriatic arthritis. Psoriasis patients with a baseline BMI of 25-29.9 kg/m² were at an adjusted 1.76-fold increased risk of later developing psoriatic arthritis, compared with psoriasis patients having a BMI of less than 25. For those with a BMI of 30-34.9 kg/m², the risk of subsequent psoriatic arthritis was increased 2.04-fold. And for those with a baseline BMI of 35 kg/m² or more, the risk was increased 2.42-fold in analyses adjusted for age, sex, psoriasis duration and severity, history of trauma, and diabetes.

In contrast, the risk of developing psoriatic arthritis wasn’t significantly different between psoriasis patients who were nonsmokers, ex-smokers, or current smokers. And while there was a significantly increased risk of developing psoriatic arthritis in psoriasis patients who were current drinkers, compared with nondrinkers, the risk in ex-drinkers and heavy drinkers was similar to that in nondrinkers, a counterintuitive finding Dr. McHugh suspects was a distortion due to small numbers.

While the observed relationship between baseline BMI and subsequent risk of psoriatic arthritis was informative, it only tells part of the story, since body weight so often changes over time. Dr. McHugh and his coinvestigators had data on change in BMI over the course of 10 years of follow-up in 15,627 psoriasis patients free of psoriatic arthritis at the time their psoriasis was diagnosed. The researchers developed a BMI risk calculator that expressed the effect of change in BMI over time on the cumulative risk of developing psoriatic arthritis.

“We were able to show that if, for instance, you started with a BMI of 25 at baseline and ended up with a BMI of 30, your risk of psoriatic arthritis goes up by 13%, whereas if you start at 30 and come down to 25, your risk decreases by 13%. And the more weight you lose, the greater you reduce your risk of developing psoriatic arthritis,” the rheumatologist explained in an interview.

Indeed, with more extreme changes in BMI over the course of a decade following diagnosis of psoriasis – for example, dropping from a baseline BMI of 36 kg/m² to 23 kg/m² – the risk of developing psoriatic arthritis fell by close to 30%.

Dr. McHugh reported having no financial conflicts regarding this study, funded by the U.K. National Institute for Health Research.

[email protected]

SOURCE: Green A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2134.