Safety profile of topical diclofenac: a meta-analysis of blinded, randomized, controlled trials in musculoskeletal conditions

Abstract

Background:

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are clinically proven for the management of musculoskeletal conditions. It is important that prescribers and patients are aware of the safety profile of topical NSAIDs.

Objectives:

To evaluate the risk of adverse events (AEs) associated with topical diclofenac for the treatment of acute and chronic musculoskeletal conditions.

Design:

Systematic review and meta-analysis of blinded, randomized, placebo-, vehicle- or active-controlled trials.

Results:

The risk of any type of AE experienced with topical diclofenac was slightly higher compared with placebo/vehicle (RR 1.11), but was more than 50% lower than the risk observed with active topical comparators (RR 0.53). Absolute risk values indicated differences in the risk of AEs depending on the diclofenac formulation used; in particular, lower rates of local skin reactions were observed with diclofenac patches (e.g. 2.5% in placebo/vehicle-controlled studies) and gels (4.2%) compared with diclofenac solutions containing dimethylsulfoxide (34.2%). Dry skin/crusting and rash were the most common local skin reactions reported (9.0% and 3.0% of patients, respectively, in placebo/vehicle-controlled studies), which were usually mild-to-moderate and self-resolving. The discontinuation rate due to local skin reactions with topical diclofenac (1.9%) was low and comparable with non-active comparators (0.7%), and the tolerability of topical diclofenac treatment was rated as ‘good’ to ‘excellent’ by >90% physicians and patients.

Conclusions:

Topical diclofenac appears to be generally well tolerated for cutaneous use in acute and chronic musculoskeletal conditions.

Key words::

• Adverse events
• Meta-analysis
• Non-steroidal anti-inflammatory drugs
• Randomized controlled trials
• Skin reactions
• Topical diclofenac

Transparency

Declaration of funding

Novartis Consumer Health sponsored the professional medical writer, Deborah Nock (DPP-Cordell Ltd), who developed the manuscript, and paid for fast-track submission to CMRO.

Declaration of financial/other relationships

G.F. is an employee of Novartis Consumer Health, SA, Switzerland.

Peer reviewers may receive honoraria from CMRO for their review work. No relevant financial relationships have been declared by any peer reviewer for this manuscript.

Prof Rod Taylor and Prof Maibach received consultancy payment from Novartis Consumer Health for input into the study.

Acknowledgements

The authors would like to thank the following people for their assistance in providing further clarification regarding adverse events in their particular study: Dr Peter Jenoure43, Dr Judith May33, Dr Saranatra Waikakul48 and Dr Lisa Grierson22,37–39,60. The draft of this manuscript was prepared by a professional medical writer (Deborah Nock, DPP-Cordell Ltd), with full review and approval by all authors.