Derry Sheena, Moore R Andrew, Rabbie Roy
Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Cochrane Database Syst Rev. 2012 Sep 12;9(9):CD007400. doi: 10.1002/14651858.CD007400.pub2.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken orally, but they are also available in topical preparations to be applied to or rubbed onto the skin of a painful joint, typically one affected by arthritis, with the aim of relieving pain locally. Topical NSAIDs are widely used in some parts of the world for acute and chronic painful conditions, but have not been universally accepted until recently. One of the problems has been that older clinical studies were generally short, lasting four weeks or less, and short duration studies are not regarded as adequate in ongoing painful conditions.
To examine the use of topical NSAIDs in chronic musculoskeletal pain, focusing on studies of high methodological quality, and examining the measured effect of the preparations according to study duration. The principal aim was to estimate treatment efficacy in longer duration studies of at least 8 weeks.
A series of electronic searches, together with bibliographic searches, and searches of in-house databases were combined with electronic searches of clinical trial registers and manufacturers of topical NSAIDs, or companies known to be actively researching topical NSAIDs. There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily.
Randomised, double blind studies with placebo or active comparators, where at least one treatment was a topical NSAID product, in any topical formulation (cream, gel, patch, solution), in studies lasting at least two weeks.
Two review authors independently assessed study quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk (RR) and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment.
Information was available from 7688 participants in 34 studies from 32 publications; 23 studies compared a topical NSAID with placebo. Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal conditions. The best data were for topical diclofenac in osteoarthritis, where the NNT for at least 50% pain relief over 8 to 12 weeks compared with placebo was 6.4 for the solution, and 11 for the gel formulation. There were too few data of good quality to calculate NNTs for other individual topical NSAIDs compared with placebo. Direct comparison of topical NSAID with an oral NSAID did not show any difference in efficacy. There was an increase in local adverse events (mostly mild skin reactions) with topical NSAIDs compared with placebo or oral NSAIDs, but no increase in serious adverse events. Gastrointestinal adverse events with topical NSAID did not differ from placebo, but were less frequent than with oral NSAIDs.A substantial amount of data from unpublished studies was unavailable. Much of this probably relates to formulations that have never been marketed.
AUTHORS' CONCLUSIONS: Topical NSAIDs can provide good levels of pain relief; topical diclofenac solution is equivalent to that of oral NSAIDs in knee and hand osteoarthritis, but there is no evidence for other chronic painful conditions. Formulation can influence efficacy. The incidence of local adverse events is increased with topical NSAIDs, but gastrointestinal adverse events are reduced compared with oral NSAIDs.
非甾体抗炎药(NSAIDs)通常口服,但也有局部用制剂,可涂抹或揉搓在疼痛关节的皮肤上,通常是受关节炎影响的关节,目的是局部缓解疼痛。局部用NSAIDs在世界某些地区被广泛用于治疗急慢性疼痛病症,但直到最近才被普遍接受。问题之一是,以往的临床研究通常时间较短,持续四周或更短,而短期研究对于持续存在的疼痛病症而言被认为是不够的。
研究局部用NSAIDs在慢性肌肉骨骼疼痛中的应用,重点关注方法学质量高的研究,并根据研究持续时间考察制剂的实测效果。主要目的是评估至少8周的较长时间研究中的治疗效果。
一系列电子检索,结合文献检索以及内部数据库检索,并与临床试验注册库和局部用NSAIDs制造商或已知积极研究局部用NSAIDs的公司进行电子检索相结合。每个治疗组必须至少有10名参与者,且治疗至少每天应用一次。
随机、双盲研究,有安慰剂或活性对照,其中至少一种治疗为局部用NSAIDs产品,剂型不限(乳膏、凝胶、贴剂、溶液),研究持续至少两周。
两位综述作者独立评估研究质量和有效性,并提取数据。达到各结局的参与者数量用于计算与安慰剂或其他活性治疗相比的相对危险度(RR)以及治疗所需人数(NNT)或伤害所需人数(NNH)。
从32篇出版物中的34项研究的7688名参与者中获取了信息;23项研究将局部用NSAIDs与安慰剂进行了比较。局部用NSAIDs在减轻慢性肌肉骨骼疾病引起的疼痛方面比安慰剂显著更有效。最佳数据来自双氯芬酸局部用制剂治疗骨关节炎,与安慰剂相比,在8至12周内至少50%缓解疼痛的NNT,溶液剂型为6.4,凝胶剂型为11。与安慰剂相比,其他个别局部用NSAIDs的高质量数据太少,无法计算NNT。局部用NSAIDs与口服NSAIDs的直接比较未显示疗效有任何差异。与安慰剂或口服NSAIDs相比,局部用NSAIDs的局部不良事件有所增加(大多为轻度皮肤反应),但严重不良事件未增加。局部用NSAIDs的胃肠道不良事件与安慰剂无差异,但比口服NSAIDs更少见。大量未发表研究的数据无法获取。其中大部分可能与从未上市的剂型有关。
局部用NSAIDs可提供较好的疼痛缓解效果;双氯芬酸局部用溶液在膝和手部骨关节炎中的效果与口服NSAIDs相当,但在其他慢性疼痛病症中尚无证据支持。剂型可影响疗效。局部用NSAIDs的局部不良事件发生率增加,但与口服NSAIDs相比,胃肠道不良事件减少。