There is some evidence that topical nonsteroidal anti-inflammatory drugs (NSAIDs) are more effective compared with placebo at improving short-term pain relief and function (up to 8 weeks) for people with osteoarthritis (mainly of the knee). There are limited data that compare the efficacy and safety of topical NSAIDs and oral NSAIDs in people with osteoarthritis, but topical NSAIDs may be as effective as oral NSAIDs at reducing pain in people with osteoarthritis of the knee. With respect to adverse effects, topical NSAIDs may be less likely than oral NSAIDs to cause gastrointestinal adverse effects in the first 12 weeks of use, although topical NSAIDs are associated with skin irritation. The RCT data do not allow a conclusive judgement on whether using topical NSAIDs reduces the incidence of serious NSAID-related adverse effects, but they seem to be preferred to using oral NSAIDs as early treatment for osteoarthritis, particularly for people who do not have widespread painful osteoarthritis. No data were found comparing the risks and benefits of topical NSAID use with paracetamol.

• The National Institute for Health and Clinical Excellence (NICE) looked at studies that investigated the efficacy and safety of topical NSAIDs compared with oral NSAIDs or placebo with respect to symptoms, function, and quality of life in adults with osteoarthritis. Two systematic reviews and two additional RCTs on topical NSAIDs were appraised [Lin et al, 2004; Trnavsky et al, 2004; Niethard et al, 2005; Towheed, 2006].

Topical NSAIDs compared with placebo

• A systematic review (13 RCTs, n = 1412) investigated the efficacy of topical NSAIDs compared with placebo in people with osteoarthritis [Lin et al, 2004]. Literature searches were performed up to July 2005.
• Meta-analysis found that compared with placebo, topical NSAIDs:
• Significantly reduced pain in weeks 1 and 2 (effect size 0.41, 95% CI 0.18 to 0.63, p < 0.05).
• Did not significantly reduce pain in weeks 3 and 4 (effect size 0.08, 95% CI –0.04 to 0.2, p-value not reported).
• As well as different drugs being used in the trials, there were also differences in the osteoarthritis site.
• Another systematic review (four RCTs, n = 1412) investigated the efficacy and safety of topical diclofenac solution compared with placebo in people with osteoarthritis of the knee [Towheed, 2006]. Literature searches were performed up to February 2005.
• Meta-analysis found that compared with placebo, over a mean of 8.5 weeks, topical diclofenac:
• Significantly reduced WOMAC pain scores (SMD –0.33, 95% CI –0.48 to –0.18).
• Significantly improved WOMAC stiffness scores (SMD –0.30, 95% CI –0.45 to –0.15).
• Significantly improved physical function scores (SMD –0.35, 95% CI –0.50 to –0.20).
• The first subsequent RCT (n = 50) investigated the efficacy and safety of ibuprofen 5% cream compared with placebo in people with osteoarthritis of the knee [Trnavsky et al, 2004].
• Compared with placebo, topical ibuprofen cream was found to be statistically significantly better in terms of:
• Pain at rest.
• Pain on motion.
• Overall pain.
• Patient function.
• Global assessment.
• In terms of safety, no adverse events or withdrawals were reported in either group.
• The second RCT (n = 238) investigated the efficacy of topical diclofenac gel compared with placebo in people with osteoarthritis of the knee [Niethard et al, 2005].
• Compared with placebo, topical diclofenac gel was found to statistically significantly:
• Reduce pain intensity.
• Improve overall response.
• Improve WOMAC scores.

Topical NSAIDs compared with oral NSAIDs

• A systematic review (13 RCTs, n = 1412) investigated the efficacy of topical NSAIDs compared with oral NSAIDs in people with osteoarthritis [Lin et al, 2004]. Literature searches were performed up to July 2005.
• An RCT (n = 622) compared topical diclofenac with oral diclofenac for 12 weeks.
• Oral diclofenac significantly improved WOMAC function score compared with topical diclofenac.
• There was no significant difference in WOMAC pain, WOMAC stiffness, or WOMAC physical function scores, or in patient global assessment.
• The authors considered that there were no clinically relevant differences between the two treatments.
• Topical diclofenac was found to be more favourable compared with oral diclofenac in terms of gastrointestinal and severe gastrointestinal adverse events. However, oral diclofenac was found to be more favourable compared with dry skin reactions and rash.
• Meta-analyses comparing adverse events with topical NSAIDs versus oral NSAIDs found:
• The rate ratio of local skin adverse reactions was significantly greater in people taking topical NSAIDs compared with oral NSAIDs.
• No significant difference between oral and topical NSAIDs in the number of people with adverse events, GI adverse events, or central nervous system adverse events.
• Additional RCT analyses were performed but their findings did not provide any further insight into differences in efficacy and safety between topical and oral NSAIDs.

Economic analyses

• NICE evaluated studies that conducted economic evaluations involving topical NSAIDs. Comparing topical ibuprofen with oral ibuprofen, the NICE guideline development group concluded that:
• In a population at low risk of adverse events, oral ibuprofen is likely to be a cost-effective treatment compared with topical ibuprofen.
• In a higher risk population, treatment with topical ibuprofen is likely to be less expensive than treatment with oral ibuprofen.

[National Collaborating Centre for Chronic Conditions, 2008]