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

OBJECTIVE: Assess guselkumab+golimumab combination versus guselkumab monotherapy in participants with active PsA and inadequate response to tumor necrosis factor inhibitors (TNFi-IR). METHODS: Adults with active TNFi-IR PsA (≥3 tender/swollen joints) were randomized (2:1) to subcutaneous guselkumab (100mg)+golimumab (50mg) combination (N=59) or guselkumab monotherapy (N=32) every-4-weeks (Q4W) through W20. The primary endpoint was W24 minimal disease activity (MDA) achievement. Additional endpoints included ACR20/50/70 response rates; improvements in psoriasis/dactylitis/enthesitis; changes in patient-reported physical function; and impact of screening CRP on MDA/ACR50 response. RESULTS: At baseline, participants had a median of 13/8 tender/swollen joints and psoriatic body surface area of 3%; 23% had dactylitis. At W24, 29% and 22% of participants achieved MDA with guselkumab+golimumab combination and guselkumab monotherapy, respectively (odds ratio [OR], 90% confidence interval: 1.4 [0.6, 3.3]; P=0.557); 44% and 22% achieved ACR50 (nominal P=0.034). Participants with CRP ≥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 W24. Combination therapy was associated with higher ACR20 (66% vs. 44%)/ACR70 (27% vs. 16%) responses and greater physical function improvements than monotherapy. Psoriasis/dactylitis/enthesitis improvements were similar across groups. No new safety signals, and no tuberculosis/opportunistic infections, occurred through W36. 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, could derive clinically meaningful benefits with guselkumab+golimumab combination therapy, with no new safety concerns, warranting further investigation.