Paudel Misti L, Li Ruogu, Naik Chinmayi, Shadick Nancy, Weinblatt Michael E, Solomon Daniel H
Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Rheumatology (Oxford). 2025 Mar 1;64(3):1102-1110. doi: 10.1093/rheumatology/keae318.
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.
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.
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.
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.
估计有5%-20%的类风湿关节炎（RA）患者多种治疗均失败，被视为“难治性”（D2T），这给风湿病学家带来了重大的临床挑战。欧洲抗风湿病联盟（EULAR）的一个特别工作组在2021年提出了D2T-RA的定义。我们将EULAR的D2T定义应用于一组确诊为RA的患者队列中以评估患病率，并将D2T-RA参与者的临床特征与匹配的对照组进行比较。
使用来自布莱根妇女医院类风湿关节炎序贯研究（BRASS）纵向登记处的数据。如果参与者符合EULAR的定义，则被分类为D2T。非D2T-RA患者的对照组与每例D2T患者按2:1进行匹配，并在描述性分析中评估特征差异。使用泊松回归估计D2T的患病率。
在1581例RA参与者中，我们估计D2T-RA的患病率为每100人中有14.4例（95%CI：12.8，16.3），在1021例使用生物制剂/靶向合成改善病情抗风湿药（DMARD）的患者中，患病率为每100人中有22.3例（95%CI：19.9，25.0）。我们观察到D2T-RA与非D2T-RA对照组在人口统计学、合并症和RA疾病活动方面存在一些差异。BRASS所有参与者中不同的EULAR次要标准导致D2T-RA患病率在每100人中有0.6至17.5例之间。
EULAR提出的D2T-RA定义可识别未达到治疗目标的RA患者。未来的研究应探索这些患者的异质性并评估结局，以为旨在制定更有效的RA管理方案的未来研究设计提供信息。
