Experts Highlight Recent Breakthroughs in Psoriatic Arthritis

Bruce Jancin

March 30, 2021

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.

A Role for Apremilast in Oligoarticular Disease?

Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast's numeric superiority in outcomes compared to methotrexate in this exploratory study wasn't subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, "The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it's not as effective as methotrexate."

"This study shows to me that, even though it's a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug," said Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

"Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic," he noted.

Ogdie concurred.

"If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine," she said.

A final point: "We really don't have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That's why trialists enroll patients with high joint count numbers," according to the rheumatologist.

No Increased Risk of Solid Cancers in PsA Patients Treated With TNF Inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

"I like this study a lot because it's specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it's a different population," Kavanaugh said.

Ogdie-Beatty said, "I talk to my patients about this particular study or the same group's earlier lymphoma study all the time."

"I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don't have an increased risk of malignancy. This kind of information is going to be helpful," observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.

Greater Efficacy for Biologics in Males Than Females With PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

"These are randomized patients, so you really shouldn't see these big differences in minimal disease activity," Ogdie-Beatty noted. "The question is why do men seem to respond better to therapy than women? I don't think it's the fibromyalgia-ness. There's probably some biologic rationale for this that we just don't understand yet. Maybe hormonal interactions."

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Ruderman added.

"That gender difference is not likely to be huge if you're looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there's an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that's not real but is based on gender and not response to the drug," he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis "very interesting."

"We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward," he proposed.

Ogdie-Beatty, Kavanaugh, and Ruderman reported having financial relationships with numerous pharmaceutical companies.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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