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.