Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis
Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis
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DOI：
10.1016/s0140-6736(17)31744-0
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发表时间：
2017-07-08
期刊：
影响因子：
168.9
通讯作者：
Trelle, Sven
中科院分区：
文献类型：
--
作者：
da Costa, Bruno R.;Reichenbach, Stephan;Trelle, Sven
背景非甾体抗炎药（NSAID）是骨关节炎疼痛治疗的主要药物。我们的目的是评估不同的制剂和剂量的非甾体抗炎药对骨关节炎疼痛的有效性在网络荟萃analysis.Methods对于这个网络荟萃分析，我们认为随机试验比较以下任何干预措施：非甾体抗炎药，扑热息痛，或安慰剂，治疗骨关节炎疼痛。我们检索了科克伦对照试验中心注册库（CENTRAL）和1980年1月1日至2015年2月24日期间发表的试验相关文章的参考文献列表，每组至少100例患者。预先设定的主要和次要结局是疼痛和身体功能，并在治疗开始后的7个时间点重复提取两次。我们使用了多变量贝叶斯随机效应模型的扩展，用于在试验水平上进行随机效应的混合多治疗比较。对于主要分析，使用一级随机游走来解释试验中的多个随访结局数据。在分析中单独考虑使用不同每日总剂量的制剂。为了评估一个潜在的剂量反应关系，我们使用了特定的协变量假设线性对数relative dose.Findings我们确定了8973手稿，从我们的搜索，其中76个随机试验，共58 451例患者被纳入本分析。考虑了23个节点，涉及7种不同的NSAID或对乙酰氨基酚，以及特定的每日给药剂量或安慰剂。与安慰剂相比，所有制剂，无论剂量如何，均改善了疼痛症状的点估计值。对于6种干预（双氯芬酸150 mg/天，依托考昔30 mg/天、60 mg/天和90 mg/天，罗非昔布25 mg/天和50 mg/天），与安慰剂的差异等于或低于预先规定的最低临床重要疼痛减轻效应（效应量[ES] -0.37）的概率至少为95%。在批准的最大日剂量中，双氯芬酸150 mg/天（ES-0. 57，95%可信区间[CrI]-0. 69至-0. 45）和依托考昔60 mg/天（ES-0. 58，-0. 74至-0. 43）是最佳干预的概率最高，达到最小临床重要差异的概率均为100%。治疗效果随着药物剂量的增加而增加，但线性剂量效应的相应检验仅对萘普生有显著性（p=0.034）。我们没有发现任何证据表明治疗效果随治疗时间而变化。模型拟合良好，试验间异质性和不一致性在所有分析中均较低。所有试验均被认为对患者设盲的偏倚风险较低。效果估计没有改变敏感性分析与两个额外的统计模型和会计方法的质量标准在meta-regression analysis.Interpretation的基础上，现有的数据，我们看到没有作用的单药对乙酰氨基酚治疗骨关节炎患者的剂量无关。我们提供了可靠的证据，证明双氯芬酸150 mg/天是目前最有效的NSAID，可改善疼痛和功能。然而，鉴于这些药物的安全性，医生在为个体患者选择制剂和剂量时，需要考虑我们的结果以及所有已知的安全性信息。
Background Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta-analysis.Methods For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose-response relation, we used preparation-specific covariates assuming linearity on log relative dose.Findings We identified 8973 manuscripts from our search, of which 76 randomised trials with a total of 58 451 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] -0.37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES -0.57, 95% credibility interval [CrI] -0.69 to -0.45) and etoricoxib 60 mg/day (ES -0.58, -0.74 to -0.43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for naproxen (p=0.034). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis.Interpretation On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients.