Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Rheumatology (Oxford). 2014 Sep;53(9):1664-8. doi: 10.1093/rheumatology/keu158. Epub 2014 Apr 12.
The aim of this study was to evaluate the survival on treatment with second-line biologic therapy in RA patient non-responders to TNF inhibitors (TNFis) by comparing treatments with a second anti-TNF (cycling strategy) or with agents with a different mechanism of action (MoA; swap strategy).
RA patients treated with biologics since 1999 who stopped a first-line TNFi and started a second-line biotherapy were included in this cohort study. After adjusting for propensity scores, drug retention rates were calculated using the Kaplan-Meier method. The log-rank test was used to compare survival curves and the Cox regression model was used to compare risk for discontinuation between the two groups.
Two hundred and one patients discontinued the first TNFi, switching to a second anti-TNF [n = 119 (59.2%)] or to abatacept [n = 26 (31.7%)], rituximab [n = 40 (48.8%)] or tocilizumab [n = 15 (18.3%)]. Drug survival was significantly higher in the swap group than in the cycling group (P < 0.0001). After adjustment for propensity scores, probability of treatment retention in the swap group was significantly higher (hazard ratio = 2.258, 95% CI 1.507, 3.385), even after stratification according to the reason for the first TNFi discontinuation (P = 0.005). No significant differences emerged when comparing the retention rates of different MoAs (P = 0.51) in the swap group.
In the clinical practice setting, the best option for managing TNFi non-responders seems to be swapping to a different MoA, with no differences between abatacept, rituximab and tocilizumab, irrespective of the reason for first TNFi discontinuation.
本研究旨在比较使用第二种抗 TNF(循环策略)或不同作用机制(MoA;转换策略)的药物治疗对 TNF 抑制剂(TNFis)应答不佳的 RA 患者的二线生物治疗的生存情况。
本队列研究纳入了自 1999 年以来接受生物制剂治疗且停用一线 TNFi 并开始二线生物治疗的 RA 患者。通过调整倾向评分,使用 Kaplan-Meier 法计算药物保留率。采用对数秩检验比较生存曲线,采用 Cox 回归模型比较两组停药风险。
201 例患者停用一线 TNFi,转换为第二种抗 TNF [n = 119(59.2%)]或阿巴西普 [n = 26(31.7%)]、利妥昔单抗 [n = 40(48.8%)]或托珠单抗 [n = 15(18.3%)]。转换组的药物生存显著高于循环组(P < 0.0001)。调整倾向评分后,转换组的治疗保留率显著更高(风险比=2.258,95%CI 1.507,3.385),即使在根据一线 TNFi 停药原因进行分层后(P = 0.005)也是如此。在转换组中,不同 MoA 的保留率无显著差异(P = 0.51)。
在临床实践中,管理 TNFis 无应答者的最佳选择似乎是转换为不同的 MoA,无论一线 TNFi 停药的原因如何,阿巴西普、利妥昔单抗和托珠单抗之间均无差异。