Interleukin-6 Receptor Inhibition With Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis With Inadequate Response to Disease-Modifying Antirheumatic Drugs The Tocilizumab in Combination With Traditional Disease-Modifying Antirheumatic Drug Therapy Study
Interleukin-6 Receptor Inhibition With Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis With Inadequate Response to Disease-Modifying Antirheumatic Drugs The Tocilizumab in Combination With Traditional Disease-Modifying Antirheumatic Drug Therapy Study
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DOI：
10.1002/art.23940
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发表时间：
2008-10-01
影响因子：
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通讯作者：
Gomez-Rein, Juan J.
中科院分区：
文献类型：
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作者：
Genovese, Mark C.;McKay, James D.;Gomez-Rein, Juan J.
目标。目的观察人源化抗白细胞介素6受体抗体联合常规抗风湿药物治疗活动期类风湿关节炎(RA)的疗效和安全性。在111期双盲、安慰剂对照、多中心(Tocilizumab联合传统DMARD疗法)研究中，共有1220名患者被随机分组(2：1比率)。患者继续服用稳定剂量的DMARDS，每4周接受托西珠单抗8 mg/kg或安慰剂(对照组)治疗24周。在第24周，根据美国风湿病学会的20%改善标准(ACR20)，tocilizumab加DMARD组的有效率显著高于对照组(61%比25%；P<；0.0001)。次要终点包括50%或70%改善(ACR50/70)，28个关节疾病活动性评分(DAS28)，DAS28个缓解反应(DAS28=L不良事件(AE))，而对照组为61%。导致退出研究的血管紧张素转换酶很少见(tocilizumab组4%的患者和对照组2%的患者)。Tocilizumab组和对照组严重不良反应发生率分别为6.7%和4.3%，严重感染发生率分别为2.7%和1.9%。Tocilizumab组和对照组的丙氨酸转氨酶水平分别有4%和1%的患者升高，分别为23%和6%，丙氨酸转氨酶水平从基线正常到正常上限的3倍。在研究期间，16名患者开始了降脂治疗。接受tocilizumab治疗的患者中有3.7%的患者出现3级中性粒细胞减少，而对照组中无1例出现3级中性粒细胞减少，也没有4级中性粒细胞减少的报告。Tocilizumab联合任何一种DMARDS评估在减轻对这些药物反应不足的患者的关节和全身症状方面是安全和有效的。
Objective. To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA).Methods. A total of 1,220 patients were randomized (2:1 ratio) in the phase 111, double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy) study. Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks for 24 weeks.Results. At week 24, the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20% improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group than in the control group (61% versus 25%; P < 0.0001). Secondary end points including 50% or 70% improvement (ACR50/70), the Disease Activity Score in 28 joints (DAS28), DAS28 remission responses (DAS28 = l adverse event (AE), compared with 61% of patients in the control group. AEs leading to withdrawal from the study were infrequent (4% of patients in the tocilizumab group and 2% of those in the control group). Serious AEs occurred in 6.7% and 4.3% of patients in the tocilizumab and control groups, respectively, and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the alanine aminotransferase level, from normal at baseline to > 3-fold the upper limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of those in the control group, and elevated total cholesterol levels were observed in 23% and 6% of patients, respectively. Sixteen patients started lipid-lowering therapy during the study. Grade 3 neutropenia occurred in 3.7% of patients receiving tocilizumab and none of the patients in the control group, and no grade 4 neutropenia was reported.Conclusion. Tocilizumab combined with any of the DMARDs evaluated was safe and effective in reducing articular and systemic symptoms in patients with an inadequate response to these agents.