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Topical NSAIDs for joint disease
  • Relevant BNF section: 10.3.2


Over 20 proprietary topical preparations of non-steroidal anti-inflammatory drugs (NSAIDs) are now available, both 'over the counter' and on prescription. They are licensed for the treatment of pain due to 'non-serious' arthritic conditions and/or soft tissue injuries. In the early 1990s, we could find little evidence to support the use of these products rather than simple analgesics or oral NSAIDs for acute soft tissue injuries, and even less for chronic inflammatory and degenerative joint diseases.1,2 Here, we reconsider the place of topical NSAIDs, concentrating on their use in chronic arthritic conditions.

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  • Relevant BNF section: 10.3.2


Topical NSAIDs available on prescription include benzydamine, diclofenac, felbinac, ibuprofen, ketoprofen, mucopolysaccharide polysulphate + salicylic acid and piroxicam preparations, and these come in a range of formulations such as creams, foams, gels, or sprays. Of these, all but one (topical benzydamine) are licensed for use in chronic arthritic conditions.

There is little reliable published information on how topical NSAIDs are distributed after application to the skin. The relevant summaries of product characteristics often refer only to 'data on file', some of which is animal-based rather than clinical evidence. Of interest, in a published study involving 10 patients, after topical application of diclofenac to one knee and placebo to the other, levels of diclofenac in both knees differed little, with at least 85% of the diclofenac in the joints apparently reaching them via the circulation rather than by tissue penetration.3 The results of several other small studies suggest that, compared with oral administration of an NSAID, topical administration leads to lower concentrations of the drug in the plasma, synovial fluid and fascia but higher concentrations in the subcutaneous tissue and underlying muscle.1,2,48 However, they also suggest that levels in synovial fluid with topical NSAIDs may approach the therapeutically effective levels expected from oral use of the drugs, although multiple applications may be needed.1,2,48

Clinical studies

There are few reliable trials of topical NSAIDs in chronic arthropathies. In particular, studies involving comparison with other treatments (e.g. rubefacients, paracetamol, or rest, ice, compression and elevation), or of combined use with oral treatments are lacking. A systematic review of treatment with topically applied NSAIDs has included 25 controlled trials (13 with placebo controls and 12 with active controls) lasting 1-4 weeks and involving a total of 2433 patients with a chronic pain condition (i.e. single-joint arthritis or other rheumatological disorders).9 All the available topical NSAIDs were included in at least one of the placebo-controlled trials but none was included in more than two, so combined estimates for individual products could not be calculated. It is not clear from the review which trials were conducted under double-blind conditions.

In only seven of the 13 placebo-controlled studies was the topical NSAID investigated more effective than placebo in terms of pain reduction. In the overall analysis of the placebo-controlled studies, treatment efficacy was assessed using 'dichotomous' outcomes (i.e. presence or absence of at least 50% improvement in pain). Accordingly, one of the 13 studies, which assessed a combination gel containing 3% diclofenac + 2.5% sodium hyaluronate was excluded from the overall analysis because the trial outcomes were not 'dichotomous'.10 In this study, pain relief did not differ between the active treatment group and the placebo group (p=0.057). Pooled relative benefit for the other 12 placebo-controlled trials used in the analysis was around 2 and the number needed to treat was around 3.

Of the 12 studies in the systematic review comparing a topical NSAID with an active control, only three studies compared topical NSAIDs with oral NSAIDs. No difference in terms of effectiveness was seen between the different preparations, but in any case, according to the authors of the systematic review, the studies were too small to allow reliable comparison. The other nine studies compared one topical NSAID with another but no detailed analysis of these trials was given.

Limitations of the systematic review include the heterogeneity of the conditions studied and the dichotomous outcomes measured in the individual trials. These factors limit the applicability of the overall results in routine management. In addition, the authors of the review reported being unable to get all existing unpublished data and therefore could not exclude publication bias.

Unwanted effects

Local unwanted effects with topical NSAIDs typically include itching, rashes, erythema and eczema, which have been estimated to occur in around 1-4% of patients.4,9 Gastrointestinal unwanted effects, including bleeding in patients with current or past ulceration,1113 asthma14,15 or acute renal impairment1618 have been reported rarely with one or more topical NSAIDs. Studies of the long-term unwanted effects of topical NSAIDs, or of their relative safety compared to oral NSAIDs, are lacking.

Costs of topical NSAIDs to the NHS

The cost to the NHS of 100g of a topical NSAID ranges from about £1 to £7 depending on the product. According to the Prescription Pricing Authority (PPA), just under 3 million prescription items were dispensed for topical NSAIDs in both 1997 and 1998; the net ingredient cost of these items for each year was nearly £20million.


We remain unconvinced of the value of topical NSAIDs for the treatment of chronic arthritic pain. There is some evidence from short-term studies that topical NSAIDs are more effective than placebo in reducing underlying joint pain but the data are weak. There is little or no published evidence on topical NSAIDs either in comparison to, or in combination with, standard treatments such as paracetamol, rubefacients or oral NSAIDs. More data are needed on the long-term efficacy and relative systemic safety of topical NSAIDs. We see no reason for topical NSAIDs to be available on the NHS as a treatment for chronic arthritic pain.


[M=meta-analysis; R=randomised controlled trial]

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