Clinical Edge Journal Scan

Commentary: Evaluating new and established treatments for PsA, July 2023

Dr. Chandran scans the journals, so you don't have to!

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Vinod Chandran, MBBS, MD, DM, PhD

Research papers published this month have focused on the therapeutics of psoriatic arthritis (PsA). Despite the availability of a number of targeted therapies, a significant proportion of patients have persistent disease activity and poor quality of life. Novel therapies are needed to address this unmet need. Janus kinase (JAK) inhibitors are now proven to be efficacious in the treatment of PsA. Brepocitinib is a novel inhibitor of both tyrosine kinase 2 (TYK2) and JAK1. Mease and colleagues reported results from a phase 2b, dose-ranging, parallel treatment group trial including 218 patients with active PsA who were randomly assigned to receive either brepocitinib (60, 30, or 10 mg once daily) or placebo. At week 16, American College of Rheumatology (ACR) 20 response was achieved by a significantly higher proportion of patients receiving brepocitinib at doses of 30 mg (66.7%; P = .0197) and 60 mg (74.6%; P = .0006) compared with placebo (43.3%), with the response being maintained through week 52. Overall, 12 serious adverse events were reported in the brepocitinib arm (30 mg and 60 mg) by week 52. No major adverse cardiovascular events or deaths were reported. Thus, brepocitinib (30 mg and 60 mg) shows promise and should be further evaluated in phase 3 trials. Head-to-head comparison with a JAK1 inhibitor (eg, upadacitinib) or a TYK2 inhibitor (eg, deucravacitinib) would be required to evaluate the safety and efficacy of dual TYK2-JAK1 inhibition compared with either one of the JAK inhibitors alone.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

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