S1663 Inhibition of Structural Damage Progression With Guselkumab in Participants With Active Psoriatic Arthritis: Results Through Week 24 of the Phase 3b, Randomized, Double-Blind, Placebo-Controlled APEX Study

Introduction: Extraintestinal manifestations(EIMs), eg, joint involvement and psoriatic arthritis (PsA), are common in pts with IBD and may be associated with more severe IBD. Guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, is approved to treat CD, UC, PsA, and psoriasis. No studies have prospectively evaluated the efficacy of GUS on EIMs in IBD; data from psoriatic studies may be informative. The Phase 3b, randomized, double-blind, placebo-controlled APEX study evaluated clinical and radiographic outcomes in GUS-treated pts with active PsA. Here, we report Week 24 (W24) results. Methods: APEX enrolled biologic naïve adults with active PsA (≥3 tender & ≥3 swollen joints; C-reactive protein ≥0.3 mg/dL) and ≥2 erosive joints on radiographs of hands and feet despite previous non-biologic DMARDs, apremilast, or NSAIDs. Pts were randomized 5:7:7 to SC GUS 100 mg every 4 weeks; GUS 100 mg at W0/4, then every 8 weeks; or PBO every 4 weeks. Multiplicity-controlled endpoints were the proportion of pts achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) (primary) and the mean change from baseline (BL) in PsA-modified van der Heijde-Sharp (vdH-S) score at W24 (secondary). Efficacy analyses included all randomized pts except those from sites unable to support key study operations (N = 1020; every 4 weeks: 273, every 8 weeks: 371, PBO: 376); safety analyses included all treated pts through W24 (N = 1054). Results: BL characteristics were similar across groups. Mean duration of PsA (7.3 yrs), PsA-modified vdH-S total (27.0) and erosion (13.5) scores, and tender (20.7) and swollen (11.9) joint counts indicated established, highly active joint disease. Primary and major secondary endpoints were met. Significantly greater proportions of GUS every 4 weeks (67%), and every 8 weeks (68%) pts vs PBO (47%) achieved ACR 20 at W24 (both P < 0.001). Pts receiving GUS every 4 weeks and every 8 weeks had significantly less radiographic progression vs PBO at W24 (LSM changes in PsA-modified vdH-S scores: 0.55, 0.54 vs 1.35; P = 0.002, < 0.001, respectively). Similar response patterns occurred at W24 for changes in joint space narrowing and erosion scores, pts with no radiographic progression, and other clinical outcomes. AE rates were similar among groups (37-42%); SAE rates were low (2-3%), and no new safety signals were identified. Conclusion: GUS improved arthritis and inhibited structural damage progression in pts with active PsA. Findings may inform treatment decisions in pts with IBD with articular EIMs related to psoriatic disease.