Objectives To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA).
Methods PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies.
Results 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=−0.30, 95% CI −0.40 to –0.20) and improving function (SMD=−0.35, 95% CI −0.45 to –0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=−0.81, 95% CI −1.12 to –0.52) and piroxicam was most effective for functional improvement (SMD=−1.04, 95% CI −1.60 to –0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs.
Conclusions Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.
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CZ and JW contributed equally.
GL and WZ contributed equally.
Contributors GL, WZ, CZ and JW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: GL, WZ, CZ. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: CZ, JW. Critical revision of the manuscript for important intellectual content: WZ, GL, MSMP, MD, AS. Statistical analysis: JW, XL. Study supervision: GL, WZ.
Funding This work was supported by the National Natural Science Foundation of China (81472130, 81672225, 81601941, 81501923, 81772413, 81702207, 81702206), the Postdoctoral Science Foundation of Central South University (182130), the Young Investigator Grant of Xiangya Hospital, Central South University (2016Q03, 2016Q06), the Scientific Research Project of the Development and Reform Commission of Hunan Province (1199), the Scientific Research Project of Science and Technology Office of Hunan Province (2013SK2018), the Key Research and Development Program of Hunan Province (2016JC2038), the Xiangya Clinical Big Data System Construction Project of Central South University (45), the Clinical Scientific Research Foundation of Xiangya Hospital, Central South University (2015L03), the Fundamental Research Funds for the Central Universities of Central South University (2015zzts112) and the Natural Science Foundation of Hunan Province (2017JJ3491, 2017JJ3492).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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