Increasing proportion and more favourable outcomes of seronegative rheumatoid arthritis: analysis of the IORRA cohort from 2000 to 2021.

INTRODUCTION/OBJECTIVES: To investigate longitudinal trends in the proportion of seronegative rheumatoid arthritis (RA) and to compare clinical outcomes between seronegative and seropositive patients in a Japanese single-centre cohort. METHOD: We included 4,354 RA patients with a disease duration < 4 years from the Institute of Rheumatology, Rheumatoid Arthritis cohort. Seronegativity was defined as the absence of both rheumatoid factor (RF) and anti-citrullinated peptide (CCP) antibody. We assessed the association between enrolment period and seronegativity using multivariable logistic regression. A mixed-effects model was used to compare 3-year trends in Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and the Japanese version of the Health Assessment Questionnaire (J-HAQ) scores between serostatus groups. RESULTS: The proportion of seronegative RA increased from 14.4% in 2000-2010 to 17.9% in 2011-2021. The later period was associated with seronegativity (adjusted odds ratio [95% confidence interval]: 1.32 [1.08-1.61]), negative RF (1.23 [1.05-1.45]), and negative anti-CCP antibody (1.31 [1.11-1.56]). At 3 years, seronegative patients had better mean (95% confidence interval) CDAI (4.50 [3.48-5.53] vs. 5.57 [4.66-6.48]), DAS28-ESR (2.13 [1.93-2.32] vs. 2.54 [2.37-2.71]), and J-HAQ (0.43 [0.33-0.54] vs. 0.52 [0.42-0.61]) compared with seropositive patients. The proportions of patients achieving J-HAQ remission were comparable between the groups. CONCLUSIONS: The proportion of seronegative RA has increased significantly over time. Seronegative patients demonstrate a favourable disease course with a higher rate of remission compared with seropositive patients, thus identifying them as a distinct RA subgroup. Key Points • The proportion of seronegative rheumatoid arthritis increased over time in a large Japanese cohort. • Patients with seronegative rheumatoid arthritis had significantly higher rates of clinical remission over 3 years. • The increasing proportion and distinct prognosis of seronegative rheumatoid arthritis may require specific management strategies.