Long‐term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin‐23, through 2 years: results from a phase 3, randomized, double‐blind, placebo‐controlled study conducted in biologic‐naïve patients with active psoriatic arthritis

Objective: Assess long-term efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in patients with active psoriatic arthritis (PsA) from the Phase-3 DISCOVER-2 trial. Methods: In DISCOVER-2, patients with active PsA (≥5 swollen and ≥5 tender joints; CRP ≥0.6 mg/dL) despite prior nonbiologic therapy were randomized to: guselkumab 100mg every-4-weeks (Q4W); at Week0, Week4, and Q8W; or placebo➔guselkumab Q4W at Week24. Efficacy assessments included ≥20%/50%/70% improvement in ACR components (ACR20/50/70), Investigator’s Global Assessment of psoriasis score=0 (IGA=0; indicating complete skin clearance), enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score) resolution, and changes in PsA-modified van der Heijde-Sharp (vdH-S) radiographic scores. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through Week100; safety assessments continued through Week112. Results: Of 739 randomized and treated patients, 652 (88%) completed treatment through Week100. Across groups of guselkumab-treated patients (including placebo➔Q4W) ACR20 (68%-76%), ACR50 (48%-56%), ACR70 (30%-36%), and IGA=0 (55%-67%) responses and enthesitis (62%-70%) and dactylitis (72%-83%) resolution rates at Week100 indicated amelioration of arthritis signs/symptoms and extra-articular manifestations was durable through 2years. Mean changes in PsA-modified vdH-S scores from Week52-100 (0.13-0.75) indicated the low rates of radiographic progression observed among guselkumab-treated patients at earlier timepoints extended through Week100. Through Week112, 8% (5.8/100 patient-years) and 3% (1.9/100 patient-years) of 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; one death occurred (road traffic accident). Conclusion: In biologic-naïve PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2years