Influence of Biological Sex on Participant Characteristics, Guselkumab Efficacy and Radiographic Progression in Active Psoriatic Arthritis: Post Hoc Analysis of Three Randomized Trials.

INTRODUCTION: Psoriatic arthritis (PsA) is a heterogeneous disease, and clinical manifestations can differ between sexes. Sex-disaggregated baseline characteristics, guselkumab efficacy, and radiographic progression were assessed in a pooled cohort of randomized controlled trial (RCT) participants with active PsA. METHODS: Post hoc analyses of DISCOVER-1 (N = 381), DISCOVER-2 (N = 739), and COSMOS (N = 285) assessed sex-related baseline characteristics differences. Week (W) 24 clinical response rates with guselkumab 100 mg at W0/W4/every 8W (Q8W) were compared between sexes using multivariate logistic regression. In DISCOVER-2, multivariate repeated-measures mixed models evaluated associations between sex and radiographic progression with guselkumab Q4W + Q8W through W100, and between early (W8) response in joint disease activity with guselkumab Q4W + Q8W and radiographic progression, stratifying by sex. RESULTS: Females were older; had higher body mass index; longer PsA duration; less severe psoriasis; more prevalent enthesitis; and reported more fatigue, pain, and functional impairment. Analyses adjusting for sex-specific differences in baseline characteristics showed no significant sex impact on guselkumab clinical response. Through W100, males exhibited significantly greater radiographic progression than females in unadjusted and adjusted models. Early clinical improvement in joint disease activity with guselkumab afforded significantly less radiographic progression through W100 in males (p = 0.0288) and numerically less in females. CONCLUSIONS: Despite being associated with significant differences in characteristics at baseline, sex had no independent effect on guselkumab clinical efficacy in this RCT cohort. The known independent association between male sex and radiographic progression was confirmed; males exhibited a stronger relationship between early improvement in joint disease activity and lower long-term rates of radiographic progression. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03162796, NCT03158285, NCT03796858.