Male Sex Predicts a Favorable Outcome in Early ACPA-Negative Rheumatoid Arthritis: Data From an Observational Study

Objective The aim of the present study was to investigate whether the relationship between sex and clinical outcomes in early rheumatoid arthritis (RA) varies by autoantibody status. Methods Two inception cohorts of consecutive patients with early RA (ie, symptom duration ≤ 12 months) in the southern region of Sweden were investigated. Patients were stratified by anticitrullinated peptide antibody (ACPA) status. The primary outcome was remission (Disease Activity Score in 28 joints [DAS28] < 2.6) at 12 months. Secondary outcomes were remission at 6 months and European Alliance of Associations for Rheumatology good response at 6 and 12 months compared to baseline. In logistic regression models, which were adjusted for age, DAS28 values, and Health Assessment Questionnaire values at baseline, the relationship between sex and clinical outcomes, stratified by ACPA status, was investigated. Results In total, 426 patients with early RA were included: 160 patients were ACPA negative and 266 patients were ACPA positive. At 12 months, 27.1% (38/140) of females and 24.1% (13/54) of males with ACPA-positive RA achieved DAS28 remission. In ACPA-negative RA, 16.0% (13/81) of females and 48.6% (18/37) of males achieved DAS28 remission at 12 months. Males had higher odds of reaching remission at 12 months in the ACPA-negative patient group (pooled adjusted odds ratio [OR] 4.79, 95% CI 1.97-11.6), but not in the ACPA-positive group (pooled adjusted OR 1.06, 95% CI 0.49-2.30). Conclusion Male sex was associated with better clinical outcomes in ACPA-negative early RA, but not in ACPA-positive early RA. The poor outcomes in females with early seronegative RA suggest that this represents a difficult-to-treat patient group.