COSMOS: Guselkumab for patients with TNFi-IR in PsA

Many patients with PsA are treated with TNFis, but a large proportion of patients receiving their first TNFi do not achieve an ACR20 response within 6 months of treatment, requiring further therapies. 

The phase IIIb randomized, placebo-controlled COSMOS study (NCT03796858) was initiated to evaluate the multi-domain effectiveness of guselkumab, an IL-23p19 inhibitor, in patients with PsA and inadequate response to TNFi using various composite indices over 48 weeks (DAPSA, DAS28, PsARC, PASDAS, GRACE, mCPDAI, MDA, and VLDA). 

In total, 285 patients were randomized 2:1 to receive guselkumab (n=189) or placebo (n=96), with the placebo group crossing over to guselkumab at Week 24. Results were published in Oxford Rheumatology by Gossec et al.

Key learnings

Guselkumab significantly improved PsA disease activity across all composite indices compared with placebo by Week 24. Improvements increased through Week 48, and >80% of patients who achieved LDA at Week 24 maintained it at Week 48.

Joint-specific indices showed earlier response (as early as Week 4). Lower baseline disease activity predicted better achievement of LDA/remission, and patients with only one prior TNFi responded better than those with two.

Overall, 53% of placebo-randomized patients switched to guselkumab at Week 24. Placebo patients who switched to guselkumab at Week 24 showed similar improvements by Week 48, supporting guselkumab’s consistent efficacy.

In this study, guselkumab was effective across all domains of PsA, including skin, joints, enthesitis, and dactylitis, and was a viable treatment option for patients with PsA and prior TNFi failure. This supports the use of treat-to-target strategies using composite indices in real-world settings.