Effect of Guselkumab Administered Every 8 Weeks in Patients With Active Psoriatic Arthritis Persists Between Consecutive Doses and is Durable: Post Hoc Analysis of a Phase 3, Randomized, Double-blind, Placebo-controlled Study

Background The efficacy of guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, in patients (pts) with active psoriatic arthritis (PsA) has been previously shown across a variety of PsA domains and baseline (BL) pt characteristics[1-3]. Given the central role of the IL-23/Th17 pathway in PsA, it has been hypothesized that IL-23 inhibition with GUS may provide persistent and durable clinical responses between doses and over time when administered every 8 weeks (Q8W). Objectives To assess at the pt level the persistence of effect of GUS Q8W between doses and its durability of effect over time. Methods DISCOVER-2 was a phase 3, randomized, double-blind, placebo (PBO)-controlled study that enrolled pts with active PsA despite standard therapies. Pts were biologic-naïve, had tender and swollen joint counts (TJC/SJC) each ≥5, and C-reactive protein (CRP) ≥0.6 mg/dL. Pts were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. In the current analysis, only pts treated with GUS Q8W (N=248) were included. Persistence of effect between consecutive dosing visits was described with the proportion of pts maintaining response (as defined below) in outcomes assessed during dosing visits (Disease Activity index for PsA [DAPSA], clinical DAPSA [cDAPSA]). Durability of effect was assessed with the Kaplan Meier estimator of the survival function where each pt contributed follow-up from the first time of achievement of clinical response within the 24-week period and the time of loss of response or last available assessment through W100. Definitions of clinical response included achievement of clear/almost clear skin (investigator’s global assessment [IGA] 0/1; among pts with BL IGA>1) or minimal clinically important improvements (MCII) in DAPSA (≥7.25), cDAPSA (≥5.7), skin visual analog scale (VAS; ≥15 mm), and PsA Disease Activity Score (PASDAS; ≥0.8). Results Between consecutive (Q8W) dosing visits through W52, the proportion of pts maintaining response ...