Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study).
Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study).
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DOI：
10.1136/annrheumdis-2017-211878
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发表时间：
2018-03
影响因子：
27.4
通讯作者：
Nishimoto N
中科院分区：
文献类型：
--
作者：
Nakaoka Y;Isobe M;Takei S;Tanaka Y;Ishii T;Yokota S;Nomura A;Yoshida S;Nishimoto N
目的：探讨白细胞介素-6受体抗体tocilizumab治疗高须动脉炎（Takayasu arteritis， TAK）的疗效和安全性。在过去12周内复发的TAK患者通过口服糖皮质激素治疗诱导缓解。在这项双盲安慰剂对照试验中，患者被随机分配为1:1，每周接受tocilizumab 162mg皮下注射或安慰剂，从第4周开始，口服糖皮质激素逐渐减少10% /周至最低0.1 mg/kg/天，直到19例患者复发。主要终点是TAK复发的时间，定义为以下≥2项：客观全身症状，主观全身症状，炎症标志物升高，血管体征和症状或缺血症状。意向治疗和安全人群包括18例tocilizumab治疗和18例安慰剂治疗的患者。按方案组（PPS）包括16例tocilizumab治疗组和17例安慰剂治疗组。在8例tocilizumab治疗组和11例安慰剂治疗组中，基于复发的意向治疗人群（主要终点）TAK复发时间hr为0.41 (95.41% CI 0.15至1.10;p=0.0596)， PPS组为0.34 （95.41% CI 0.11至1.00;p=0.0345）。次要终点，仅通过Kerr定义和临床症状评估的复发时间，与主要终点一致。1例托珠单抗治疗和2例安慰剂治疗的患者报告了严重不良事件。没有严重感染，也没有死亡。虽然没有达到主要终点，但结果表明tocilizumab在TAK复发的时间上优于安慰剂，没有新的安全性问题。需要进一步的研究来证实tocilizumab对难治性TAK患者的疗效。japiccti - 142616。
To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK). Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients relapsed. The primary endpoint was time to relapse of TAK, defined as ≥2 of the following: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms or ischaemic symptoms. The intent-to-treat and safety populations included 18 tocilizumab-treated and 18 placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab-treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41 (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary endpoints, time to relapse assessed by Kerr’s definition and clinical symptoms only, were consistent with the primary endpoint. Serious adverse events were reported in one tocilizumab-treated and two placebo-treated patients. There were no serious infections and no deaths. Although the primary endpoint was not met, the results suggest favour for tocilizumab over placebo for time to relapse of TAK without new safety concerns. Further investigation is warranted to confirm the efficacy of tocilizumab in patients with refractory TAK. JapicCTI-142616.
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