Multidomain Efficacy and Safety of Guselkumab Through 1 Year in Patients With Active Psoriatic Arthritis With and Without Prior Tumor Necrosis Factor Inhibitor Experience: Analysis of the Phase 3, Randomized, Placebo-Controlled DISCOVER-1 Study.

Abstract

Objective: To evaluate efficacy and safety of the interleukin-23p19-subunit inhibitor, guselkumab, in DISCOVER-1 patients with active psoriatic arthritis (PsA) by prior use of tumor necrosis factor inhibitor (TNFi).

Methods: The phase 3, randomized, placebo-controlled DISCOVER-1 study enrolled patients with active PsA (swollen joint count ≥3, tender joint count ≥3, and C-reactive protein level ≥ 0.3 mg/dl) despite standard therapies; approximately one-third could have received two or fewer prior TNFi. Patients were randomized to 100 mg of guselkumab every 4 weeks (Q4W); 100 mg of guselkumab at week 0, at week 4, and every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Efficacy end points of ≥20% and ≥50% improvement in individual American College of Rheumatology (ACR) criteria and achieving the minimal disease activity (MDA) components were summarized by prior TNFi status.

Results: In DISCOVER-1, 118 (31%) patients previously received one or two TNFi. As previously reported, rates for acheiving ≥20% improvement in the composite ACR response at week 24 and week 52 were similar in TNFi-naive and TNFi-experienced patients randomized to guselkumab Q4W (76% and 68%, respectively) and Q8W (61% and 58%, respectively). Similar trends were observed for response rates of ≥20% and ≥50% improvement in individual ACR criteria and for achieving individual MDA components at week 24; TNFi-naive patients were more likely to achieve end points related to physical function and pain than TNFi-experienced patients. Overall, response rates were maintained or increased through week 52 regardless of prior TNFi use. Through week 60 in guselkumab-treated TNFi-naive and TNFi-experienced patients, 62% and 64%, respectively, reported one or more adverse events (AEs); 4% and 6% had serious AEs, respectively.

Conclusion: Through 1 year, 100 mg of guselkumab Q4W and Q8W provided sustained improvements across multiple domains in both TNFi-naive and TNFi-experienced patients with active PsA.