Department of Rheumatology, 1 avenue Molière, Strasbourg University Hospital, National Centre For Rare Systemic Autoimmune Diseases, 67000 Strasbourg, France
CNRS UPR3572, Immunologie, Immunopathologie et Chimie Thérapeutique, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, Strasbourg University, 67000 Strasbourg, France.
BMJ. 2019 Jan 24;364:l67. doi: 10.1136/bmj.l67.
To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis.
Population based prospective study.
53 university and 54 non-university clinical centres in France.
3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months.
Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis.
The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LED), which measures the difference between average duration of survival without failure.
Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LED 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events.
Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.
比较三种非肿瘤坏死因子（TNF）α抑制剂（利妥昔单抗、阿巴西普和托珠单抗）治疗类风湿关节炎的疗效和安全性。
基于人群的前瞻性研究。
法国 53 家大学和 54 家非大学临床中心。
3162 名符合 1987 年美国风湿病学会标准的成年类风湿关节炎患者（>18 岁），入组法国风湿病学会的三个注册研究之一；无严重心血管疾病、活动或严重感染或严重免疫缺陷，随访至少 24 个月。
开始静脉注射利妥昔单抗、阿巴西普或托珠单抗治疗类风湿关节炎。
主要终点是 24 个月时无药物失败的药物保留率。失败定义为全因死亡；停止使用利妥昔单抗、阿巴西普或托珠单抗；开始使用新的生物制剂或联合使用传统的疾病修饰抗风湿药物；或与基线时连续两次就诊相比，皮质类固醇剂量增加>10mg/d。由于非比例风险，治疗效果以无失败的预期寿命差异（LED）表示，该指标衡量无失败生存时间的平均差异。
利妥昔单抗组的无失败生存平均时间为 19.8 个月，阿巴西普组为 15.6 个月，托珠单抗组为 19.1 个月。与阿巴西普相比，利妥昔单抗（LED4.1，95%置信区间 3.1 至 5.2）和托珠单抗（3.5，2.1 至 5.0）的平均持续时间更长，且与利妥昔单抗相比，托珠单抗的不确定性较大（-0.7，-1.9 至 0.5）。在无死亡、癌症或严重感染以及主要不良心血管事件的平均生存时间方面，未发现治疗方法之间存在差异。
在常规实践中随访的难治性类风湿关节炎成年患者中，与阿巴西普相比，利妥昔单抗和托珠单抗在两年时改善结局的效果更大。
