Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study
Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study
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DOI：
10.1007/s10067-015-2988-9
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发表时间：
2016-04-01
影响因子：
3.4
通讯作者：
Montero, Enrique
中科院分区：
文献类型：
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作者：
Chopra, Arvind;Chandrashekara, S.;Montero, Enrique
本研究的目的是评估itolizumab联合甲氨蝶呤治疗对甲氨蝶呤反应不足的活动性类风湿关节炎（RA）患者的安全性和有效性。在这项开放标签的2期研究中，70名符合美国风湿病学会（ACR）标准且潜伏性结核病阴性的患者被随机分为四个组：每周0.2、0.4或0.8 mg/kg伊托单抗联合口服甲氨蝶呤和单独使用甲氨蝶呤（2:2:2:1）。患者治疗12周，随访期间单独使用甲氨蝶呤12周。12周的依托单抗治疗耐受性良好。44例患者报告了不良事件（ae）；除6例严重ae外，其余均为轻度或中度ae。输注相关反应主要发生在第一次输注后，第11次输注后无反应发生。血清中未检测到抗伊托单抗抗体。在完整的分析集中，所有伊托单抗剂量都显示出疗效。12周时，50%的患者达到ACR20, 58.3%的患者达到中度或良好的28关节计数疾病活动评分（DAS-28）反应；在第24周，22名和31名患者出现了这些反应。简表36健康调查和健康评估问卷残疾指数得分有显著改善。总体而言，itolizumab联合甲氨蝶呤在12周内对RA具有良好的耐受性和有效性，在整个24周的评估期内持续有效。（印度临床试验登记处，“http://ctri.nic.in/Clinicaltrials/login.php”， CTRI/2008/091/000295）。
The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, "http://ctri.nic.in/Clinicaltrials/login.php", CTRI/2008/091/000295).