University Hospitals of Geneva, Geneva, Switzerland.
Lancet. 2013 May 4;381(9877):1541-50. doi: 10.1016/S0140-6736(13)60250-0. Epub 2013 Mar 18.
Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis.
We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01119859.
We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (-3·3) than in the adalimumab group (-1·8) patients (difference -1·5, 95% CI -1·8 to -1·1; p<0·0001). 16 of 162 (10%) patients in the adalimumab group versus 19 of 162 (12%) in the tocilizumab group had serious adverse events. More patients in the tocilizumab group than in the adalimumab group had increased LDL-cholesterol, increased alanine aminotransferase concentrations, and reduced platelet and neutrophil counts.
Tocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings.
F Hoffmann-La Roche.
约三分之一接受生物制剂治疗的类风湿关节炎患者接受的是单药治疗。白细胞介素 6 受体信号抑制剂托珠单抗已在多项临床试验中作为单药治疗进行了研究。我们评估了托珠单抗单药治疗与阿达木单抗单药治疗类风湿关节炎患者的疗效和安全性。
我们在北美、南美、澳大拉西亚和欧洲的 15 个国家的 76 个中心进行了这项随机、双盲、平行分组、4 期优效性研究。我们招募了年龄至少 18 岁、患有严重类风湿关节炎 6 个月或以上、对甲氨蝶呤不耐受或不适合继续甲氨蝶呤治疗的患者。患者以 1:1 的比例（分组大小为 4）随机分配接受托珠单抗 8mg/kg 体重静脉注射每 4 周一次加安慰剂皮下注射每 2 周一次，或阿达木单抗 40mg 皮下注射每 2 周一次加安慰剂静脉注射每 4 周一次，共 24 周。研究者、患者和申办者人员对分组情况设盲。主要终点是从基线到第 24 周时使用 28 个关节疾病活动度评分（DAS28）的变化。这项试验在 ClinicalTrials.gov 注册，编号为 NCT01119859。
我们筛选了 452 名患者，纳入了 326 名患者。意向治疗人群包含 325 名患者（托珠单抗组 163 名，阿达木单抗组 162 名）。托珠单抗组（-3.3）的第 24 周 DAS28 自基线的平均变化显著大于阿达木单抗组（-1.8）（差值-1.5，95%CI-1.8 至-1.1；p<0.0001）。阿达木单抗组有 16 名（10%）患者和托珠单抗组有 19 名（12%）患者发生严重不良事件。托珠单抗组比阿达木单抗组更多的患者出现 LDL-胆固醇升高、丙氨酸氨基转移酶浓度升高、血小板和中性粒细胞计数降低。
托珠单抗单药治疗在不适合使用甲氨蝶呤的类风湿关节炎患者中，在减轻疾病的体征和症状方面优于阿达木单抗单药治疗。托珠单抗和阿达木单抗的不良事件谱与之前的发现一致。
罗氏制药。
