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Am Fam Physician. 2017;96(9):573-574

Author disclosure: No relevant financial affiliations.

Clinical Question

Are topical nonsteroidal anti-inflammatory drugs (NSAIDs) more effective than oral NSAIDs or placebo for chronic musculo-skeletal pain associated with osteoarthritis in adults?

Evidence-Based Answer

Topical diclofenac and ketoprofen are slightly more effective than placebo for relieving chronic pain associated with osteoarthritis in adults. Evidence is lacking to determine the effectiveness of topical NSAIDs compared with oral NSAIDs.1 (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Osteoarthritis is one of the most common presentations in outpatient primary care practices, with the knee being the joint most often involved.2 Topical NSAIDs are used to treat chronic musculoskeletal pain because they are thought to be as effective as and have fewer adverse effects than oral NSAIDs. In this updated Cochrane review, the authors sought to determine the effectiveness of topical NSAIDs vs. placebo and oral NSAIDs, as well as compare adverse effect profiles.1

This Cochrane review included 39 studies with a total of 10,631 patients who had knee osteoarthritis.1 All studies were considered to have at least moderate methodologic quality and small to moderate risk of bias. The primary outcome of the review was clinical success, defined by any of the following: (1) reduction of pain by at least 50%, (2) a very good or excellent global assessment rating of treatment, or (3) no pain or slight pain with movement of the joint. Secondary outcomes included adverse effects or withdrawals from treatment. No reports addressed topical NSAID use for other joints or for soft tissue pain. All studies included dosing of topical NSAIDs at least once daily, but dosages varied or were not always recorded.

Of the 39 studies, 33 compared a topical NSAID with placebo. Of these 33 studies, only those with topical ketoprofen and diclofenac had enough participants to allow for data pooling. Clinical success with diclofenac was better than with placebo (relative risk [RR] = 1.9; 95% confidence interval [CI], 1.5 to 2.3), with a number needed to treat (NNT) of 5 (95% CI, 3.7 to 7.4). Plaster formulations in the form of a medicated patch demonstrated more clinical success than placebo (NNT = 3.1; 95% CI, 2.3 to 4.6), as did medication in the form of gels or solutions (NNT = 7.5; 95% CI, 4.6 to 20). Ketoprofen also improved clinical success compared with placebo (NNT = 6.9; 95% CI, 5.4 to 9.3).

Nearly all adverse effects were due to skin irritation. Only diclofenac demonstrated a significant risk of adverse effects (number needed to harm [NNH] = 16; 95% CI, 12 to 23). Patients treated with diclofenac also were more likely than those treated with placebo to stop treatment (NNH = 51; 95% CI, 30 to 170).

Only five studies included a blinded comparison between topical and oral NSAID administration. Three of the studies used topical diclofenac; the others used piroxicam (Feldene) and ketoprofen. The oral NSAID used was either ibuprofen, diclofenac, or celecoxib (Celebrex). Analysis of these five studies revealed no statistically significant difference in clinical improvement between the oral and topical therapies.

In the studies comparing patients treated with topical vs. oral medication, local adverse effects were more common among those using topical NSAIDs (NNH = 6.4; 95% CI, 5.3 to 8.0; five studies, 1,651 patients). Gastrointestinal adverse effects were less common in the topical NSAID group than in the oral NSAID group.

General expert consensus supports the use of topical NSAIDs as a safe and effective treatment for chronic pain associated with osteoarthritis of the hand and knee.3 The American Academy of Orthopaedic Surgeons includes topical and oral NSAIDs in its updated 2013 guideline recommendations for the treatment of knee osteoarthritis.4 The National Institute for Health and Care Excellence published a guideline in 2014 recommending a trial of topical NSAIDs for hand and knee osteoarthritis as a first-line therapy before initiating oral NSAIDs.5

The practice recommendations in this activity are available at

The opinions expressed in this paper reflect those of the authors alone and do not reflect the opinions of the Department of the Army, Defense Health Agency, the Department of Defense, or the U.S. government.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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