Selective IL-23 blocker shows remarkable efficacy in patients with psoriatic arthritis

In a phase 3, double-blind, placebo-controlled trial in adult patients with active psoriatic arthritis (PsA) who are biologic-naïve, guselkumab improved all primary and secondary outcomes [1].

“We already knew that guselkumab works nicely on the skin,” said Prof. Atul Deodhar (Oregon Health & Science University, Portland, USA). The agent was now assessed in 381 patients with active moderate-to-severe PsA. DISCOVER-2 included 739 biologic-naïve patients with moderate-to-severe disease (mean swollen/tender joints: 12/21, median C-reactive protein (CRP): 1.2 mg/dL, mean body surface area (BSA) with psoriasis: 17.4%) despite non-biologic disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were treated with guselkumab 100 mg every 4 weeks (n=245), guselkumab 100 mg every 8 weeks (n=248), or placebo (n=246). In this trial, concomitant therapy with non-biologic DMARDs, oral corticosteroids, and NSAIDs was allowed. At week 16, patients with less than 5% improvement in tender and swollen joints were allowed to increase the dose of the concomitant therapy mentioned above. The primary endpoint of the DISCOVER-2 trial was American College of Rheumatology 20% response rate (ACR20) at week 24. In addition, a couple of major secondary endpoints at week 24 were assessed, such as psoriasis response according to the Investigator´s Global Assessment (IGA=0/1 and ≥2-grade reduction) in patients with 3% or greater BSA psoriasis and IGA≥2 at baseline; changes in joint function (assessed by the Health Assessment Questionnaire without Disability Index (HAQ-DI)), psoriatic arthritis-modified van der Heijde-Sharp (vdH-S), and quality of life (assessed by the SF-36 physical component score (PCS)).

In total, 63.7% of patients assigned to guselkumab every 4 weeks and 64.1% of patients assigned to the drug every 8 weeks achieved ACR20 response at week 24 versus 32.9% of the placebo group (P<0.001 for both comparisons; see Figure). Curves for both guselkumab doses separated from placebo as early as week 4.

Figure: ACR20 response over time in the DISCOVER-2 trial [1]

 

Better joint function, skin symptoms, and quality of life

Guselkumab also improved skin symptoms of psoriasis at week 24: significantly more patients assigned to either guselkumab dose achieved IGA response versus placebo (both comparisons P<0.001). Significantly greater improvement from baseline was also seen in HAQ-DI (adjusted P<0.001) and in quality of life (adjusted P≤0.011) in both guselkumab dose regimes. Guselkumab every 4 weeks significantly reduced radiographic damage progression versus placebo. Among pooled DISCOVER-1&2 patients, a significantly higher proportion of patients treated with guselkumab every 4 and every 8 weeks compared with placebo had resolution of enthesitis or dactylitis at week 24 (all comparisons P<0.05).

Serious adverse events and serious infections occurred in 2.4% of patients assigned to guselkumab every 4 weeks and 0.7% of patients assigned to the drug every 8 weeks. All observed adverse events were consistent with the known guselkumab safety profile in psoriasis studies.

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   1. Mease P et al. Abstract L13. ACR 2019, 9-13 November, Atlanta (GA/USA).

Posted on 4 February 202024 March 2021