The burden of musculoskeletal pain and the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in its treatment. Ten underpinning statements from a global pain faculty.

This document presents the conclusions of a detailed discussion on the role of topical NSAIDs during a round table Global Pain Faculty meeting held in Amsterdam in 2019 and subsequent discussions online. The aim of this evidence-based document is to describe the impact of musculoskeletal pain both in terms of the large numbers of sufferers and its economic impact. The document considers the place of topical therapies alongside other pharmacological and non-pharmacological treatments and presents the evidence for the benefits and harms of topical NSAIDS including indicators of efficacy for three main topical NSAIDs- diclofenac, ibuprofen and ketoprofen - based on almost 15,000 participants in randomized controlled trials for acute and chronic musculoskeletal pain. These topical NSAIDs have the largest body of evidence. For acute pain, numbers needed to treat to achieve at least 50% reduction in pain are as follows with 95% confidence intervals in brackets: Diclofenac emulgel 1.8(1.5-2.1) (5170 participants), Ibuprofen gel 2.7 (1.7-4.2) (436 participants), Ketoprofen gel 2.2 (1.7-2.8) (683 participants). For chronic pain, the NNTs are Diclofenac any formulation 9.5(7-14) (5995 participants). Ketoprofen 6.9(5.5-9.3) (2573 participants). Randomized controlled trial evidence suggests that adverse events for active topical NSAIDs are similar to placebo. Finally the gaps in knowledge are considered with suggestions on how further research might help. The global pain faculty was brought together by GSK under an unrestricted educational grant.

Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain.

Aim: The objective was to systematically review the efficacy and safety of topical diclofenac in both acute and chronic musculoskeletal pain in adults.Methods: We used standard Cochrane methods. Searches were conducted in MEDLINE, EMBASE and The Cochrane Register of Studies; date of the final search was November 2018. Included studies were randomized, double blinded, with ten or more participants per treatment arm. The primary outcome of "clinical success" was defined as participant-reported reduction in pain of at least 50%. Details of adverse events (AEs) were recorded.Results: For acute pain, 23 studies (5170 participants) were included. Compared to placebo, number needed to treat (NNT) for different formulations were as follows: diclofenac plaster, 4.7 (95% CI 3.7-6.5); diclofenac plaster with heparin, 7.4 (95% CI 4.6-19); and diclofenac Emulgel, 1.8 (95% CI 1.5-2.1). 4.1% (78/1919) reported a local AE. For chronic pain, 21 studies (26 publications) with 5995 participants were included. Formulations included gel, solution with or without DMSO, emulsion and plaster. A clinical success rate of ∼60% (NNT 9.5 [95% CI 7-14.7]) was achieved with a variety of formulations. Local AEs (∼14%) were similar for both diclofenac and placebo.Conclusion: This systematic review of 11,000+ participants demonstrates that topical diclofenac is effective for acute pain, such as sprains, with minimal AEs. The effectiveness of topical diclofenac was also demonstrated in chronic musculoskeletal pain but with a higher NNT (worse) compared with acute pain. Formulation does play a part in effectiveness but needs further studies.