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Three Part Question

In [adult patients with musculoskeletal conditions] do [topical nonsteroidal anti-inflammatory drugs compared to placebo] provide [safe and effective pain relief]?

Clinical Scenario

A 48-year-old male presents to the emergency department (ED) with a left ankle injury. X-rays showed no acute fracture. The patient has a history of chronic alcohol abuse, hepatitis C, opioid abuse, and gastric ulcers. Therefore, he is unable to take acetaminophen, nonsteroidal anti-inflammatory drugs (NSAID), or narcotics.

Search Strategy

Medline 1966-05/18 using PubMed, CINAHL, Cochrane Library (2018), and Embase.
[(exp Anti-Inflammatory Agents, Non-Steroidal/administration and dosage) AND (exp Pain/drug therapy) AND (exp topical)]. Limit to humans and English language.

Search Outcome

77 studies were identified; one systematic review from the Cochrane Library addressed the clinical question. This review considered 61 clinical trials for inclusion. Since its publication, there have been two additional prospective RCTs published.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Serinken et al 2016 Turkey	100 ED patients with ankle sprain randomized to 2.5% ketoprofen gel (2g) or placebo.	RCT	Pain reduction at 15 minutes using a visual analog scale (VAS)	Ketoprofen 27 vs. placebo (p<0.0001)	Superiority trial, small sample size, no block randomization, no data on efficacy after 30 min.
			Pain reduction at 30 minutes (VAS)	Ketoprofen 42 vs. placebo 20 (p<0.0001)
Lai et al 2017 Germany	385 ED patients with ankle sprain randomized to 1% diclofenax/3% menthol, 1% diclofenac, 3% menthol, or placebo	RCT	Pain intensity on movement from 24 to 72 hours using area under the curve (AUC); secondary outcomes included pain relief, swelling, and complete recovery	No statistically significant difference in pain reduction as measured by the adjusted mean AUC or secondary outcomes	Long interval between injury and treatment (up to 24 hours); no stratification by time since injury; 40 patients with protocol violations
Derry et al 2015 United Kingdom	61 RCT studies (8386 participants) of adults presenting with acute musculoskeletal pain	Systematic review	Number needed to treat (NNT) to achieve a 50% reduction in pain or equivalent measure within 1 week	Diclofenac gel NNT 1.8; Ibuprofen gel NNT 3.9; Ketoprofen gel NNT 2.5	There were insufficient data to compare reliably individual topical NSAIDs with each other or the same oral NSAID; primary outcome of clinical success was not always well-defined, and was measured using different scales.

Comment(s)

Oral analgesics are commonly prescribed for the treatment of acute pain, but these agents often produce adverse systemic effects. Topical administration of NSAIDs can produce clinically effective drug concentrations at a peripherally located site of injury or inflammation, minimizing systemic absorption and adverse effects. The available evidence suggests that topical NSAIDs can be recommended for short-term pain relief in patients with acute soft tissue injuries. Gel formulations of diclofenac, ibuprofen, and ketoprofen, seem to provide the best results. Local skin reactions were generally mild and transient, and did not differ from placebo

Clinical Bottom Line

Topical NSAIDS provide adequate pain relief in acute musculoskeletal sprains, with a high safety profile.

References

1. Seriken M, Eken C, Elicabuk H. Topical Ketoprofen Versus Placebo in Treatment of Acute Ankle Sprain in the Emergency Department Foot Ankle Int 2016 Sep;37(9):989-93
2. Lai PM, Collaku A, Reed K Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial J Int Med Res 2017 Apr;45(2):647-661
3. Derry S, Moore RA, Gaskell H, McIntyre M, Wiffen PJ Topical NSAIDs for acute musculoskeletal pain in adults Cochrane Database Syst Rev 2015 Jun 11;(6):CD007402.