Sex Differences in Rheumatoid Arthritis: New Insights From Clinical and Patient-Reported Outcome Perspectives.

Objective: The disease course and burden of rheumatoid arthritis (RA) may differ between female and male individuals, but existing data on these differences are limited and often contradictory. Therefore, we investigated whether clinical outcomes and patient-reported outcomes (PROs) differ between female and male patients with RA over time.

Methods: All female (n = 286) and male (n = 139) patients with RA according to 1987 and/or 2010 criteria from Treatment in the Rotterdam Early Arthritis Cohort (tREACH), a stratified single-blinded trial with a treat-to-target (T2T) approach and fixed medication protocol, were included. Clinical outcomes include disease activity, medication usage, sustained disease-modifying antirheumatic drug (DMARD)-free remission (SDFR), and radiographic progression. In addition, the following PROs were investigated: general health, pain, functional ability, health-related quality of life, fatigue, productivity loss, and a possible depression or anxiety disorder. For comparisons over time, a mixed model or Cox proportional hazard model was used. The mixed models were adjusted for age, initial treatment, and disease activity (Disease Activity Score in 44 joints [DAS44]).

Results: Female patients had a higher DAS44 over time compared to male patients (β 0.36, 95% CI 0.25-0.47, P < 0.001), which also resulted in more treatment adjustments including use of biologic DMARDs (bDMARDs; 36% vs 24%, P < 0.001). Although not significant, first bDMARD survival seemed shorter in female patients (hazard ratio [HR] 1.4, 95% CI 0.8-2.6, P = 0.24). However, no differences were found in SDFR and radiographic progression. With regard to PROs, only functional ability differed significantly between sexes after adjusting for confounders, including disease activity (Health Assessment Questionnaire-Disability Index, β 0.10, 95% CI 0.04-0.17, P < 0.001).

Conclusion: Clinical outcomes and PROs are intertwined, and both improve with a T2T management approach. Nevertheless, female patients with RA have higher disease activity, a greater need for bDMARDs-although these have lower efficacy-and more functional impairment over time, underscoring the need for sex-specific management recommendations. (Trial registration number: ISRCTN26791028).