(ĐTĐ) – Topical diclofenac is about as effective as oral diclofenac in knee and hand osteoarthritis (OA), is probably as effective as other oral NSAIDs, and might be a safer choice for elderly patients and others at risk for gastrointestinal adverse effects, according to an intervention review published online September 12 in the Cochrane Database of Systematic Reviews.
Sheena Derry, PhD, and colleagues from the University of Oxford in the United Kingdom based their conclusions about topical NSAIDs on a review of randomized, double-blind studies with placebo or active comparators in which at least a single treatment was a topical NSAID used to treat chronic pain caused by OA, and in which treatment lasted at least 2 weeks. The analysis included data from 7688 participants in 34 studies, 23 of which compared a topical NSAID with placebo.
“Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal conditions,” the authors conclude. “Direct comparison of topical NSAID with an oral NSAID did not show any difference in efficacy.” Topical NSAIDs were associated with more local adverse events, such as mild rash, but with fewer gastrointestinal adverse events than oral NSAIDs.
For topical diclofenac, the number needed to treat (NNT) for at least 50% pain relief vs placebo was 6.4 for diclofenac solution and 11 for diclofenac gel formulation. There were insufficient data to calculate NNTs for other inpidual topical NSAIDs.
“The results presented here show clearly that high quality large studies demonstrate efficacy of topical NSAIDs in 12 week studies, with NNTs similar to those of oral NSAIDs,” the authors write.
Coauthor R. Andrew Moore, from the Pain Research Unit at Oxford University, told Medscape Medical News that in view of the low NNT for diclofenac solution, it would be reasonable for clinicians to view that formulation as good first-line therapy for hand or knee OA, especially in elderly patients.
“It is what [the National Institute for Health and Clinical Excellence] in the UK suggest in their excellent OA guideline,” Dr. Moore said. “This [is] nothing new for us, but then we have been looking at the evidence on topical NSAIDs for almost 20 years…. [And] what we said then is true now. Truer, perhaps.”
Experimental data suggest that creams are generally less effective than gels or sprays, according to the authors. “One of the features of topical NSAIDs is that formulation has the potential to play a big part in efficacy,” Dr. Moore said.
The authors write, “It is probable that topical NSAIDs exert their action both by local reduction of symptoms arising from periarticular structures, and by systemic delivery to intracapsular structures. Tissue levels of NSAIDs applied topically certainly reach levels high enough to inhibit cyclooxygenase-2. Plasma concentrations found after topical administration, however, are only a fraction (usually much less than 5%) of the levels found in plasma following oral administration. Topical application can potentially limit systemic adverse events by increasing local effects, and minimizing systemic concentrations of the drug. We know that upper gastrointestinal bleeding is low with chronic use of topical NSAIDs.”
Roy Altman, MD, professor emeritus, pision of Rheumatology, University of California, Los Angeles, reviewed the study for Medscape Medical News. “I think this Cochrane review was well done and carefully reported,” Dr. Altman said. “The data are convincing. Their results are concordant with our results from the literature and consistent with our recommendations of the American College of Rheumatology guidelines published earlier this year. I suspect topical NSAIDs will eventually be approved for over-the-counter use, as they are in Europe. That will dramatically increase their use.”
This study was supported by Oxford Pain Research in the United Kingdom. Dr. Deery and one coauthor have received research support from charities, government, and industry sources at various times. One coauthor has received research, consulting, and lecture fees from various pharmaceutical companies related to analgesics and other healthcare interventions. Dr. Altman has disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online September 12, 2012. Abstract
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