Topical NSAIDs for chronic musculoskeletal pain in adults

Background 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. Objectives 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. Search methods 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. Selection criteria 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. Data collection and analysis 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. Main results 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.