TY - JOUR T1 - Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS) JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis DO - 10.1136/annrheumdis-2021-220991 SP - annrheumdis-2021-220991 AU - Laura C Coates AU - Laure Gossec AU - Elke Theander AU - Paul Bergmans AU - Marlies Neuhold AU - Chetan S Karyekar AU - May Shawi AU - Wim Noël AU - Georg Schett AU - Iain B McInnes Y1 - 2021/11/24 UR - http://ard.bmj.com/content/early/2021/11/23/annrheumdis-2021-220991.abstract N2 - Objective To evaluate efficacy and safety of guselkumab, an anti-interleukin-23p19-subunit antibody, in patients with psoriatic arthritis (PsA) with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFi).Methods Adults with active PsA (≥3 swollen and ≥3 tender joints) who discontinued ≤2 TNFi due to IR (lack of efficacy or intolerance) were randomised (2:1) to subcutaneous guselkumab 100 mg or placebo at week 0, week 4, then every 8 weeks (Q8W) through week 44. Patients receiving placebo crossed over to guselkumab at week 24. The primary (ACR20) and key secondary (change in HAQ-DI, ACR50, change in SF-36 PCS and PASI100) endpoints, at week 24, underwent fixed-sequence testing (two-sided α=0.05). Adverse events (AEs) were assessed through week 56.Results Among 285 participants (female (52%), one (88%) or two (12%) prior TNFi), 88% of 189 guselkumab and 86% of 96 placebo→guselkumab patients completed study agent through week 44. A statistically significantly higher proportion of patients receiving guselkumab (44.4%) than placebo (19.8%) achieved ACR20 (%difference (95% CI): 24.6 (14.1 to 35.2); multiplicity-adjusted p<0.001) at week 24. Guselkumab was superior to placebo for each key secondary endpoint (multiplicity-adjusted p<0.01). ACR20 response (non-responder imputation) in the guselkumab group was 58% at week 48; >80% of week 24 responders maintained response at week 48. Through week 24, serious AEs/serious infections occurred in 3.7%/0.5% of 189 guselkumab-randomised and 3.1%/0% of 96 placebo-randomised patients; the guselkumab safety profile was similar through week 56, with no deaths or opportunistic infections.Conclusion Guselkumab significantly improved joint and skin manifestations and physical function in patients with TNFi-IR PsA. A favourable benefit–risk profile was demonstrated through 1 year.Trial registration number NCT03796858.The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu. ER -