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)

Abstract

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.

Keywords: arthritis; biological therapy; psoriatic; tumour necrosis factor inhibitors.

Figure 1

Disposition of patients through 1 year of COSMOS. EE, early escape; Q8W, every 8 weeks; TB, tuberculosis.

Figure 2

ACR20 response through week 48 of COSMOS. Proportions of randomised and treated patients achieving ACR20 response through week 24 in the Primary analysis (treatment failure rules applied) (A) and ACR20 response at week 24 across the Primary, PP and EE-correction analyses (B). After week 24, analyses were performed using non-responder imputation methods, including imputation of EE patients as non-responders (see Patients and methods). Results for the placebo→guselkumab group at week 48 are reported for patients who did not enter EE and crossed over to guselkumab at week 24. ACR20, ≥20% improvement in American College of Rheumatology response criteria; EE, early escape; GUS, guselkumab; PBO, placebo; PP, per protocol; Q8W, every 8 weeks.

Figure 3

ACR20 response at week 24 by baseline characteristics of COSMOS participants. ACR20, ≥20% improvement in American College of Rheumatology response criteria; CRP, C reactive protein; DMARD, disease-modifying antirheumatic drug; GUS, guselkumab; MTX, methotrexate; NSAID, non-steroidal anti-inflammatory drug; PBO, placebo; Q8W, every 8 weeks; TNFi, tumour necrosis factor inhibitor.

Figure 4

Key secondary outcomes through week 48 of COSMOS. Primary analysis through week 24 and post hoc NRI analysis at week 48 of LSmean change and mean change in HAQ-DI score (A), ACR50 response (B), LSmean change and mean change in SF-36 PCS score (C), and PASI100 response (D). After week 24, analyses were performed using NRI (including imputation of EE patients as non-responders in the guselkumab group; see Patients and methods). Results for the placebo→guselkumab group at week 48 are reported for patients who did not enter EE and crossed over to guselkumab at week 24. ACR50, ≥50% improvement in American College of Rheumatology response criteria; GUS, guselkumab; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; NRI, non-responder imputation; PASI100, 100% improvement in Psoriasis Area and Severity Index; PBO, placebo; Q8W, every 8 weeks; SF-36 PCS, 36-item Short-Form Health Survey Physical Component Summary.