类风湿关节炎患者中，托珠单抗或阿巴西普作为首个生物制剂治疗失败后，二线生物制剂或JAK抑制剂的药物留存情况——ANSWER队列研究
Drug retention of secondary biologics or JAK inhibitors after tocilizumab or abatacept failure as first biologics in patients with rheumatoid arthritis -the ANSWER cohort study.
作者信息
Ebina Kosuke, Hirano Toru, Maeda Yuichi, Yamamoto Wataru, Hashimoto Motomu, Murata Koichi, Takeuchi Tohru, Nagai Koji, Son Yonsu, Amuro Hideki, Onishi Akira, Jinno Sadao, Hara Ryota, Katayama Masaki, Yamamoto Keiichi, Kumanogoh Atsushi, Hirao Makoto
机构信息
Department of Musculoskeletal Regenerative Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
出版信息
Clin Rheumatol. 2020 Sep;39(9):2563-2572. doi: 10.1007/s10067-020-05015-5. Epub 2020 Mar 11.
OBJECTIVES
The aim of this multicenter, retrospective study was to clarify the retention of secondary biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis (RA) who were primarily treated by tocilizumab (TCZ) or abatacept (ABT) as first bDMARDs.
METHOD
Patients who were treated by either TCZ (n = 145) or ABT (n = 76) and then switched to either tumor necrosis factor inhibitors (TNFi), TCZ, ABT, or JAKi (including only cases switched from TCZ) from 2001 to 2019 (female 81.0%, age 59.5 years, disease duration 8.8 years; rheumatoid factor positivity 75.4%; Disease Activity Score in 28 joints using C-reactive protein 3.7; concomitant prednisolone (PSL) dose 6.0 mg/day (51.8%) and methotrexate (MTX) dose 8.0 mg/week (56.1%); 81.9% discontinued first bDMARDs due to lack of effectiveness) were included. Drug retention and discontinuation reasons were estimated at 24 months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling.
RESULTS
Drug retentions for each of the reasons for discontinuation were as follows: lack of effectiveness in TCZ-switched group (TNFi (59.5%), ABT (82.2%), and JAKi (84.3%); TNFi vs. ABT; P = 0.009) and ABT-switched group (TNFi (79.6%) and TCZ (92.6%); P = 0.053). Overall retention excluding non-toxic reasons and remission for discontinuation were TNFi (49.9%), ABT (72.7%), and JAKi (72.6%) (TNFi vs. ABT; P = 0.017) in the TCZ-switched group and TNFi (69.6%) and TCZ (72.4%) (P = 0.44) in the ABT-switched group.
CONCLUSIONS
Switching to ABT in TCZ-treated patients led to higher retention as compared with TNFi. Switching to TCZ in ABT-treated patients tended to lead to higher retention due to effectiveness, although total retention was similar as compared with TNFi. Key Point • This is the first retrospective, multi-center study aimed to clarify the retention rates of secondary bDMARDs or JAKi in patients with RA who were primarily being treated by TCZ or ABT as the first bDMARDs.
目的
这项多中心回顾性研究的目的是阐明在最初接受托珠单抗（TCZ）或阿巴西普（ABT）作为一线生物改善病情抗风湿药物（bDMARDs）治疗的类风湿关节炎（RA）患者中，二线bDMARDs或Janus激酶抑制剂（JAKi）的保留情况。
方法
纳入2001年至2019年期间接受TCZ（n = 145）或ABT（n = 76）治疗，随后换用肿瘤坏死因子抑制剂（TNFi）、TCZ、ABT或JAKi（仅包括从TCZ换用的病例）的患者（女性81.0%，年龄59.5岁，病程8.8年；类风湿因子阳性率75.4%；使用C反应蛋白的28个关节疾病活动评分3.7；同时使用泼尼松龙（PSL）剂量6.0 mg/天（51.8%）和甲氨蝶呤（MTX）剂量8.0 mg/周（56.1%）；81.9%的患者因疗效不佳停用一线bDMARDs）。使用Kaplan-Meier方法估计24个月时的药物保留率和停药原因，并通过Cox比例风险模型对潜在混杂因素进行校正。
结果
各停药原因的药物保留情况如下：TCZ换用组因疗效不佳（TNFi（59.5%）、ABT（82.2%）和JAKi（84.3%）；TNFi与ABT比较；P = 0.009）以及ABT换用组（TNFi（79.6%）和TCZ（92.6%）；P = 0.053）。TCZ换用组中，排除无毒原因和因缓解而停药后的总体保留率为TNFi（49.9%）、ABT（72.7%）和JAKi（72.6%）（TNFi与ABT比较；P = 0.017），ABT换用组中为TNFi（69.6%）和TCZ（72.4%）（P = 0.44）。
结论
与TNFi相比，TCZ治疗的患者换用ABT可导致更高的保留率。ABT治疗的患者换用TCZ由于疗效原因往往导致更高的保留率，尽管与TNFi相比总保留率相似。关键点•这是第一项回顾性、多中心研究，旨在阐明最初接受TCZ或ABT作为一线bDMARDs治疗的RA患者中二线bDMARDs或JAKi的保留率。
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