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.

Keywords: DMARDs; epidemiology; observational studies; primary care rheumatology; rheumatoid arthritis.

Figure 1.

Upset plot of the 15 most frequent intersections in EULAR sub-criterion 2. This Plot demonstrates the 15 most prevalent mutually exclusive combinations of sub-criteria to demonstrate how patients satisfied the EULAR requirement for persistent disease activity. The denominator for this figure is 228 participants meeting EULAR D2T-RA criteria. Black dots depict which criteria were being met, and black bars indicate the number of participants meeting each combination of sub-criteria. Sub-criteria included: a: moderate disease activity using Clinical Disease Activity Index (CDAI) >10 or DAS28-CRP > 3.2; b: signs of active disease using presence of extra-articular manifestations; c: inability to taper glucocorticoid dose of >6 mg/day prednisone equivalents; d: rapid radiographic progression of Sharp score change of 5 or more points; and e: RAPID3 > 3 and does not meet criteria a–d