Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Division of Rheumatology, IRCCS Policlinico San Matteo Foundation University Hospital, Viale Golgi 19, Pavia, 27100, Italy.
Arthritis Res Ther. 2024 Nov 8;26(1):192. doi: 10.1186/s13075-024-03431-5.
To investigate the frequency of difficult-to-treat (D2T) rheumatoid arthritis (RA) in patients early escalated to biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) after failure of treat-to-target with methotrexate (MTX).
From a prospective cohort of early RA, all patients with their first access in the years 2005-2018, and eventually starting a b/tsDMARD before the end of 2022, were included and followed-up until April 2024. Study outcomes included drug survival on each consecutive b/tsDMARDs, development of D2T (according to the EULAR definition and subsequent modifications), and its predictors.
Of a total cohort of 722 early RA patients treated with initial MTX and followed-up for at least 3 years from diagnosis, 155 (21.5%) had started a b/tsDMARD after a median of 19 months. In more than 70% of the cases, RA was uncontrolled despite optimal doses of MTX of ≥ 15 mg/day. The retention rates of the first and the second b/tsDMARD were approximatively 70% after 1 year but dropped to 40% after 5 years. After a median (IQR) follow up of 72.6 (34.5-134.2) months, 45 patients (29%) fulfilled the EULAR D2T criteria. At multivariable analysis, higher number of swollen joints and worse pain scores were confirmed as predictors of D2T. Furthermore, in this early RA cohort, shorter disease duration at the start of treatment with b/tsDMARDs, together with negativity for autoantibodies, were also independent predictors of D2T.
Early implementation of treatment after failure of treat-to-target with MTX may not prevent the development of D2T in RA. Patients showing early refractoriness to conventional drugs and those lacking autoantibodies are at higher risk of multiple treatment failures.
为了调查在接受甲氨蝶呤（MTX）达标治疗失败后早期升级为生物/靶向合成改善病情抗风湿药物（b/tsDMARDs）的患者中，难治性（D2T）类风湿关节炎（RA）的频率。
从早期 RA 的前瞻性队列中，纳入所有在 2005 年至 2018 年期间首次就诊且最终在 2022 年底前开始使用 b/tsDMARD 的患者，并随访至 2024 年 4 月。研究结果包括每一种连续的 b/tsDMARD 的药物生存情况、D2T 的发展（根据 EULAR 定义和随后的修改）及其预测因素。
在接受初始 MTX 治疗且从诊断起至少随访 3 年的 722 例早期 RA 患者中，有 155 例（21.5%）在中位数为 19 个月后开始使用 b/tsDMARD。在超过 70%的情况下，尽管 MTX 的最佳剂量≥15mg/天，但 RA 仍未得到控制。在第 1 年和第 2 年，第 1 次和第 2 次 b/tsDMARD 的保留率分别约为 70%，但在第 5 年降至 40%。在中位数（IQR）72.6（34.5-134.2）个月的随访后，45 例（29%）患者符合 EULAR D2T 标准。多变量分析证实，更多的肿胀关节数和更严重的疼痛评分是 D2T 的预测因素。此外，在这个早期 RA 队列中，b/tsDMARD 治疗开始时疾病持续时间较短，以及自身抗体阴性，也是 D2T 的独立预测因素。
在 MTX 达标治疗失败后早期实施治疗并不能预防 RA 中 D2T 的发生。早期对常规药物产生耐药的患者和缺乏自身抗体的患者发生多次治疗失败的风险更高。
