Treatment of osteoarthritis of the knee with a topical diclofenac solution: a randomised controlled, 6-week trial [ISRCTN53366886]

Background: Topical NSAIDs have been proven to relieve the symptoms of osteoarthritis (OA) in short-term studies ( 2 weeks). To justify its chronic use, efficacy of a topical NSAID over a longer term of study should be demonstrated. The efficacy and safety of a topical diclofenac solution over a 6-week treatment course in symptomatic primary OA of the knee was investigated. Methods: 216 men and women, age 40 - 85 years, with radiologically confirmed primary OA of the knee and a flare of pain at baseline following discontinuation of prior therapy were enrolled into this double-blind study. Participants applied either a topical diclofenac solution (Pennsaid(R)) or vehicle control solution ( carrier with no diclofenac); 40 drops 4 times daily directly to the painful knee(s), without massage, for 6 weeks. Pre-planned primary efficacy outcome measures included the core continuous variables pain relief and improved physical function measured by the Western Ontario and McMaster Universities (WOMAC) LK3.1 OA Index, and improved patient global assessment ( PGA). Secondary efficacy measure was reduced stiffness. Safety assessments included adverse events and vital signs. Results: The topical diclofenac group had a significantly greater mean change in score ( final minus baseline) compared to the vehicle control group for pain (- 5.2 vs. - 3.3, p = 0.003), physical function (- 13.4 vs. - 6.9, p = 0.001), PGA (- 1.3 vs. - 0.7, p = 0.0001) and stiffness (- 1.8 vs. - 0.9, p = 0.002). The mean difference between treatment arms (95% confidence interval [CI]) was 1.9 ( 0.7 to 3.2), 6.5 (2.5 to 10.5), 0.6 (0.2 to 0.9), and 0.9 (0.3 to 1.4), respectively. Safety analyses showed that topical diclofenac caused skin irritation, mostly minor local skin dryness, in 42/107 (39%), leading to discontinuation of treatment in 5/107 (5%) participants. Conclusion: This topical diclofenac solution demonstrated relief at 6 weeks of the symptoms of primary osteoarthritis of the knee.