Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry

Abstract Objectives An estimated 5–20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered ‘difficult-to-treat’ (D2T), posing a substantial clinical challenge for rheumatologists. A European League Against Rheumatism (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR’s D2T definition in a cohort of patients with established RA to assess prevalence, and we compared clinical characteristics of participants with D2T-RA with matched comparisons. Methods Data from the longitudinal Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry were used. Participants were classified as D2T if they met EULAR’s definition. A comparison group of non-D2T-RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. Results We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8, 16.3) per 100 persons among 1581 participants with RA, and 22.3 (95% CI: 19.9, 25.0) per 100 persons among 1021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities and RA disease activity between D2T-RA and non-D2T-RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6 to 17.5 per 100 persons. Conclusion EULAR’s proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.