Efficacy and safety of the fully human anti-tumour necrosis factor α monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis:: a 12 week, phase II study
Efficacy and safety of the fully human anti-tumour necrosis factor α monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis:: a 12 week, phase II study
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DOI：
10.1136/ard.2003.009563
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发表时间：
2003-12-01
影响因子：
27.4
通讯作者：
Kupper, H
中科院分区：
文献类型：
--
作者：
van de Putte, LBA;Rau, R;Kupper, H
目的：评估阿达木单抗（D2 E7）在长期活动性类风湿关节炎（RA）的疾病缓解抗风湿药物（DMARD）难治性患者中的疗效、剂量反应、安全性和耐受性。在一项为期12周的双盲、安慰剂对照研究中，284例患者被随机分配接受阿达木单抗20 mg每周一次皮下注射（n = 72），阿达木单抗40 mg（n = 70）或80 mg（n = 72）或安慰剂（n = 70），不伴随DMARDs.Results：阿达木单抗显著改善RA的所有疗效指标的体征和症状。每次评估时，阿达木单抗的ACR 20应答与安慰剂相比具有显著性（p ≤ 0.01）。此外，阿达木单抗治疗组达到ACR缓解的速度快于安慰剂组，阿达木单抗治疗组82/115（71%）的最终ACR 20缓解率在第2周达到。第12周时，阿达木单抗20、40和80 mg组的ACR 20应答率分别为50.7%、57.1%和54.2%，安慰剂组为10.0%（所有比较的p均小于或等于0.001）; ACR 50率分别为23.9%、27.1%和19.4%，而安慰剂组为1.4（所有比较p均小于或等于0.001）; ACR 70率分别为11.3%、10.0%和8.3%，而安慰剂组为0.0%（所有比较p均小于或等于0.05）。在所有评估中，所有阿达木单抗剂量均显著改善了所有ACR核心标准。40 mg和80 mg剂量提供了相似的获益。所有剂量的阿达木单抗通常耐受良好，仅发生轻度或中度不良事件。阿达木单抗和安慰剂的完成率分别为87%和67%.Conclusions：阿达木单抗单药治疗长期，严重的RA难治性传统DMARDs患者产生了快速，持续的反应，是安全的，耐受性良好，没有剂量限制的副作用。
Objectives: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA).Methods: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg ( n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs.Results: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p less than or equal to 0.01). Additionally, ACR responses with adalimumab were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%, respectively, versus 10.0% for placebo (p less than or equal to 0.001 for all comparisons); ACR50 rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo (p less than or equal to 0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%, respectively, versus 0.0% for placebo (p less than or equal to 0.05 for all comparisons). All adalimumab doses significantly improved all ACR core criteria at all assessments. The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was generally well tolerated, with only mild or moderate adverse events. Completion rates were 87% for adalimumab and 67% for placebo.Conclusions: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.