Guselkumab May Provide Benefit for Psoriatic Arthritis Across Multiple Domains

Laura Coates, PhD

A post-hoc analysis of the DISCOVER-1 and DISCOVER-2 trials presented at the American Academy of Dermatology (AAD) Virtual Meeting Experience supports guselkumab’s efficacy in patients with active psoriatic arthritis.

The study, led by Laura Coates, PhD, University of Leeds, used various composite indices to explore the efficacy of 2 dosing regimens: guselkumab 100 mg every 4 weeks (Q4W) and 100 mg every 8 weeks (Q8W). 

Previously published long-term results from the 2 Phase 3, double-blind, placebo-controlled trials showed that both regimens significantly improved signs and symptoms of joint and skin disease, physical function, and physical aspects of health-related quality of life (HRQoL) through weeks 24 and 52.

The studies also established the safety of the human monoclonal antibody, showing adverse events comparable to those with psoriasis who received 100 mg through 1 year.

In this current post-hoc analysis, Coates and colleagues evaluated efficacy according to the Disease Activity Index for Psoriatic Arthritis (DAPSA) and Clinical DAPSA (cDAPSA), Psoriasis Disease Activity Score (PASDAS), Modified Psoriatic Arthritis Response Criteria (mPsARC), Minimal Disease Activity (MDA) and Very Low Disease Activity (VLDA).

They analyzed all patients who were randomized to either dosing schedules or placebo. 

Patients either had ≥3 swollen and ≥3 tender joints and CRP ≥0.3 mg/dL (DISCOVER-1 inclusion criteria; n = 381) or ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. (DISCOVER-2 inclusion criteria; n = 739).

Thus, the team reported that patients who received guselkumab showed differences in response rates with placebo as early as week 8—as measured by the mPsARC or DAPSA Low Disease Activity remission endpoints. Response rates notably increased over time and were maintained through week 52.

All patients who received placebo through week 24 and switched to guselkumab Q4W achieved similar mPsARC reponse rates as those who were treated with guseklumab since baseline.

“Further, response rates determined by omitting CRP in calculating cDAPSA were similar to DAPSA results,” they wrote.

Across all studies, a higher proportion of patients on guselkumab Q4W (28%) and Q8W (30%) achieved PASDAS, versus placebo (9%). Placebo patients who switched to guselkumab at week 24 also demonstrated increased PASDAS response rates.

Similarly, higher proportions of guselkumab patients achieved MDA (23% vs 24% vs 8%, respectively), VLDA (6% vs 4% vs 1%, respectively), and remission measured by DAPSA (10% vs 8% vs 2%, respectively) or cDAPSA (13% vs 9% vs 3%, respectively).

“The sustained benefits for patients with active psoriatic arthritis across multiple domains indicate that guselkumab may offer a novel mechanism by which to provide extended improvements in the diverse manifestations of psoriatic arthritis,” Coates and team concluded.

The study, “Efficacy of Guselkumab Using Composite Endpoints in Patients With Active Psoriatic Arthritis: Domain-Specific Efficacy From DISCOVER-1 and DISCOVER-2 Phase 3 Trials,” was presented at AAD VMX 2021.