Arnold Lesley M, Williams David A, Hudson James I, Martin Susan A, Clauw Daniel J, Crofford Leslie J, Wang Fujun, Emir Birol, Lai Chinglin, Zablocki Rong, Mease Philip J
Women’s Health Research Program, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA.
Arthritis Rheum. 2012 Mar;64(3):885-94. doi: 10.1002/art.33360.
To develop responder definitions for fibromyalgia (FM) clinical trials using key symptom and function domains.
Twenty-four candidate responder definitions were developed by expert consensus and were evaluated in 12 randomized, placebo-controlled trials of 4 medications for the treatment of FM. For each definition, the treatment effects of the medication compared with placebo were analyzed using Cochran-Mantel-Haenszel tests or chi-square tests. A meta-analysis of the pooled results for the 4 medications established risk ratios to determine the definitions that best favored medication over placebo.
Two definitions performed best in the analyses. Both definitions included ≥30% reduction in pain and ≥10% improvement in physical function. The definitions differed in that one (≥30% improvement in FM [FM30] short version) included ≥30% improvement in sleep or fatigue, and the other (FM30 long version) required ≥30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was ≥15% for each medication and was significantly greater compared with placebo. The risk ratio favoring drug over placebo in the pooled analysis for FM30 version 3 (short version) was 1.50 (95% confidence interval [95% CI] 1.24-1.82; P ≤ 0.0001); the risk ratio for FM30 version 6 (long version) was 1.60 (95% CI 1.31-1.96; P ≤ 0.00001).
Among the 24 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for FM clinical trials that include assessments of key symptom and function domains may improve the sensitivity of clinical trials to identify meaningful improvements, leading to improved management of FM.
利用关键症状和功能领域制定纤维肌痛（FM）临床试验的缓解标准。
通过专家共识制定了24个候选缓解标准，并在12项针对4种治疗FM药物的随机、安慰剂对照试验中进行评估。对于每个标准，使用 Cochr an-Mantel-Haenszel检验或卡方检验分析药物与安慰剂相比的治疗效果。对这4种药物的汇总结果进行荟萃分析，确定风险比，以找出最有利于药物优于安慰剂的标准。
两项标准在分析中表现最佳。这两项标准均包括疼痛减轻≥30%和身体功能改善≥10%。这两项标准的不同之处在于，一项（FM[FM30]简版改善≥30%）包括睡眠或疲劳改善≥30%，另一项（FM30长版）要求以下症状中的2项改善≥30%：睡眠、疲劳、抑郁、焦虑或认知。在对两个版本的分析中，每种药物的缓解率均≥15%，且与安慰剂相比显著更高。在FM30版本3（简版）的汇总分析中，药物优于安慰剂的风险比为1.50（95%置信区间[95%CI]1.24 - 1.82；P≤0.0001）；FM30版本6（长版）的风险比为1.60（95%CI 1.31 - 1.96；P≤0.00001）。
在测试的24个缓解标准中，有2个被确定为在识别治疗反应方面最敏感。确定包括关键症状和功能领域评估的FM临床试验缓解标准，可能会提高临床试验识别有意义改善的敏感性，从而改善FM的管理。
