Wei Wenhui, Knapp Keith, Wang Li, Chen Chieh-I, Craig Gary L, Ferguson Karen, Schwartzman Sergio
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Discus Analytics, LLC, Spokane, WA, USA.
Adv Ther. 2017 Aug;34(8):1936-1952. doi: 10.1007/s12325-017-0578-8. Epub 2017 Jul 3.
To examine treatment persistence and clinical outcomes associated with switching from a tumor necrosis factor inhibitor (TNFi) to a medication with a new mechanism of action (MOA) (abatacept, anakinra, rituximab, tocilizumab, or tofacitinib) versus cycling to another TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) among patients with rheumatoid arthritis.
This retrospective, longitudinal study included patients with rheumatoid arthritis in the JointMan US clinical database who received a TNFi in April 2010 or later and either cycled to a TNFi or switched to a new MOA therapy by March 2015. Cox proportional hazards models were used for time to non-persistence (switching or discontinuing). An ordinary least squares regression model compared 1-year reduction from baseline for the Clinical Disease Activity Index (CDAI).
There were 332 (54.2%) TNFi cyclers and 281 (45.8%) new MOA switchers. During a median follow-up of 29.9 months, treatment persistence was 36.7% overall. Compared with new MOA switchers, TNFi cyclers were 51% more likely to be non-persistent (adjusted hazard ratio, 1.511; 95% CI 1.196, 1.908), driven by a higher likelihood of switching again (adjusted hazard ratio, 2.016; 95% CI 1.428, 2.847). Clinical outcomes were evaluable for 239 (53.3%) TNFi cyclers and 209 (46.7%) new MOA switchers. One-year mean reduction in CDAI from baseline to end of follow-up was significantly higher for new MOA switchers than TNFi cyclers (-7.54 vs. -4.81; P = 0.037), but the difference was not statistically significant after adjustment for baseline CDAI (-6.39 vs. -5.83; P = 0.607).
In this study, TNFi cycling was common in clinical practice, but switching to a new MOA DMARD was associated with significantly better treatment persistence and a trend toward greater CDAI reduction that was not significant after adjustment for baseline disease activity.
Sanofi and Regeneron Pharmaceuticals.
在类风湿关节炎患者中，研究从肿瘤坏死因子抑制剂（TNFi）转换为具有新作用机制（MOA）的药物（阿巴西普、阿那白滞素、利妥昔单抗、托珠单抗或托法替布）与换用另一种TNFi（阿达木单抗、赛妥珠单抗、依那西普、戈利木单抗或英夫利昔单抗）相比的治疗持续性和临床结局。
这项回顾性纵向研究纳入了JointMan美国临床数据库中2010年4月或之后接受TNFi治疗且在2015年3月前换用另一种TNFi或转换为新的MOA治疗的类风湿关节炎患者。采用Cox比例风险模型分析治疗不持续（换药或停药）时间。使用普通最小二乘回归模型比较临床疾病活动指数（CDAI）自基线起1年的降低幅度。
有332例（54.2%）TNFi换用者和281例（45.8%）新MOA转换者。在中位随访29.9个月期间，总体治疗持续性为36.7%。与新MOA转换者相比，TNFi换用者治疗不持续的可能性高51%（调整后风险比，1.511；95%置信区间1.196，1.908），这主要是由于再次换药的可能性更高（调整后风险比，2.016；95%置信区间1.428，2.847）。对239例（53.3%）TNFi换用者和209例（46.7%）新MOA转换者的临床结局进行了评估。新MOA转换者从基线到随访结束时CDAI一年的平均降低幅度显著高于TNFi换用者（-7.54对-4.81；P = 0.037），但在对基线CDAI进行调整后，差异无统计学意义（-6.39对-5.83；P = 0.607）。
在本研究中，TNFi换药在临床实践中很常见，但转换为新的MOA DMARD与显著更好的治疗持续性相关，且有CDAI降低幅度更大的趋势，不过在对基线疾病活动进行调整后该趋势无统计学意义。
赛诺菲和再生元制药公司。
