Rheumatology Department, Hospital Universitario La Paz, Paseo de La Castellana 261, Madrid, Spain.
Rheumatology Department, Hospital Clínic, Barcelona, Spain.
Clin Rheumatol. 2024 Sep;43(9):2817-2823. doi: 10.1007/s10067-024-07070-8. Epub 2024 Jul 16.
To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation.
Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation.
Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation.
Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival.
评估满足难治性类风湿关节炎（D2TRA）标准后使用的不同生物制剂或靶向合成的疾病修正抗风湿药物（b/tsDMARD）的生存情况，并评估与治疗停药相关的因素。
回顾性研究纳入 D2TRA 患者。通过 Kaplan-Meier 图和对数秩检验评估满足 D2TRA 后使用的 b/tsDMARD 的药物保留情况。Cox 风险模型用于确定影响停药的因素。
在纳入的 122 名患者中，75 名（61.5%）在 D2T 后继续维持治疗（后续线治疗），而 47 名（38.5%）停止治疗并需要更多连续的 b/tsDMARD 治疗。治疗的中位生存期为 78.3（7.6）个月，D2T 后生存获益更好的治疗药物是利妥昔单抗，其次是 JAKi 和 IL6Ri，而较差的生存获益与阿巴西普和 TNFi 相关。b/tsDMARD 之间存在显著差异（对数秩 p<0.01），为了评估这些差异，进行了 Cox 回归分析，将每种 b/tsDMARD 作为参考，并与其他药物进行比较。在开始治疗后 6 个月时，停止治疗的患者 DAS28 值更高[4.4（1.2）比 3.5（1.3），p=0.01]。多变量 Cox 回归模型显示，D2T 后治疗选择[HR=1.26（95%CI 1.06-1.05）]和 6 个月时 DAS28 值较低[HR=1.49（95%CI 1.16-1.52）]是与停药相关的独立危险因素。
一旦患者符合 D2TRA 标准，随后使用的 b/tsDMARD 中生存获益最好的是利妥昔单抗、JAKi 和 IL6Ri。此外，D2T 后 6 个月时的 DAS28 是药物停药的独立危险因素。
满足 D2TRA 标准后，利妥昔单抗、IL6Ri 和 JAKi 的保留率较高。
满足 D2TRA 标准后最初 6 个月的临床疾病活动是后续治疗生存的独立危险因素。
