Abstract
A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review.Studies were identified by searching electronic databases, and writing to manufacturers. We identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses.Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo.Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice.
Highlights
We believed that updating the review would improve efficacy estimates for topical NSAIDs, with a prior intent to determine efficacy for individual drugs
The NNT was 4.6 for one patient to experience improvement in chronic musculoskeletal pain at two weeks with topical NSAIDs, compared with placebo
There was no significant difference for smaller versus larger trials using 50 patients per group as a cut off (z = 0.40, p = 0.69), for preferred outcomes versus lower preference outcomes (z = 1.56, p = 0.12), or for patients with knee osteoarthritis compared with other musculoskeletal conditions (z = 0.99, p = 0.32) (Figure 2)
Summary
Searching Relevant studies were sought regardless of publication language, type, date or status. Information was pooled for the number of patients in each trial approximating at least 50% pain relief, or similar measure, for both topical NSAID and control. These were used to calculate NNT with a 95% confidence interval (CI) [10]. Sensitivity analysis Our prior intention was to perform sensitivity analyses on pooled outcomes using the z test [15] for quality score (2 versus 3 or more), validity score (8 or less versus 9 or more), trial size (less than 40 patients per group versus more than 40 patients per group), reported outcome (higher versus lower preference), drug, and condition treated (knee osteoarthritis versus other musculoskeletal). At least three studies had to be available in each category before information was pooled
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