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.

Conflict of interest statement

Competing interests: LCC has received consulting fees from AbbVie, Amgen, Biogen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB. LCC is funded by a National Institute for Health Research Clinician Scientist award. The work was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. LG has received research grants from Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, and consulting fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB. ET is an employee of Janssen Scientific Affairs, LLC. PB, MN and WN are employed by Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock and/or stock options. CSK is employed by Janssen Research & Development, LLC (a subsidiary of Johnson & Johnson) and owns Johnson & Johnson stock and/or stock options. MS is employed by Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson and owns stock in Johnson & Johnson. GS has received speaker’s honoraria from Amgen, AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis and UCB. IBMcI has received research grants and/or honoraria (all <$10 000 per annum) from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

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.