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)

Ann Rheum Dis. 2022 Mar;81(3):359-369. doi: 10.1136/annrheumdis-2021-220991. Epub 2021 Nov 24.


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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Psoriatic / physiopathology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Joints / drug effects
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Skin / drug effects
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • guselkumab

Associated data

  • ClinicalTrials.gov/NCT03796858