Combination Therapy in Participants With Active Psoriatic Arthritis Using Subcutaneous Guselkumab and Golimumab: Week 24 Results From a Phase 2a, Multicenter, Randomized, Double-Blind, Proof-of-Concept Study.

OBJECTIVE: To assess guselkumab + golimumab combination therapy versus guselkumab monotherapy in participants with active psoriatic arthritis (PsA) and inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

METHODS: Adults with active TNFi-IR PsA (three or more tender/swollen joints) were randomized (2:1) to subcutaneous guselkumab (100 mg) + golimumab (50 mg) combination therapy (n = 59) or guselkumab monotherapy (n = 32) every 4 weeks through week 20. The primary endpoint was week 24 minimal disease activity (MDA) achievement. Additional endpoints included ≥20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/50/70): improvements in psoriasis, dactylitis, and enthesitis; changes in patient-reported physical function; and impact of screening C-reactive protein (CRP) on MDA/ACR50 response.

RESULTS: At baseline, participants had a median of 13 tender and 8 swollen joints and psoriatic body surface area of 3%; 23% had dactylitis. At week 24, 29% and 22% of participants achieved MDA with guselkumab + golimumab combination therapy and guselkumab monotherapy, respectively (odds ratio [OR] 1.4 [90% confidence interval 0.6-3.3]; P = 0.557); 44% and 22% achieved ACR50 (nominal P = 0.034). Participants with CRP levels ≥0.3mg/dL (intended enrollment population) receiving combination therapy (n = 40; monotherapy n = 22) had greater odds of achieving MDA (OR 12.3; nominal P = 0.025; 32% vs 5%) and ACR50 (OR 9.6; nominal P = 0.003; 55% vs 14%) at week 24. Combination therapy was associated with higher ACR20 (66% vs 44%) and ACR70 (27% vs 16%) responses and greater physical function improvements than monotherapy. Improvements in psoriasis, dactylitis, and enthesitis were similar across groups. No new safety signals and no tuberculosis/opportunistic infections occurred through week 36.

CONCLUSION: Although the primary endpoint was not achieved, secondary endpoints and exploratory analyses suggest that participants with TNFi-IR PsA, particularly those with elevated CRP levels, could derive clinically meaningful benefits with guselkumab + golimumab combination therapy, with no new safety concerns, warranting further investigation.