A long-term, open-label study to confirm the safety of topical diclofenac solution containing dimethyl sulfoxide in the treatment of the osteoarthritic knee.

To assess the long-term safety of a topical solution of diclofenac sodium in a vehicle containing dimethyl sulfoxide (TDiclo), subjects with radiologically confirmed, symptomatic osteoarthritis of the knee(s) applied the clinical dose of TDiclo (40 drops, four times daily) to each painful knee for up to 52 weeks. Safety assessment included adverse events, skin irritation scores of the treated knee(s), ocular examinations, and routine laboratory tests. There were 793 subjects (mean age, 62.5 years) who applied TDiclo to one or both (72%) knees for an average of 204 days, including 463 subjects for 6 months and 144 for 1 year. The most frequent adverse events were at the application site with no increase in incidence with prolonged exposure: dry skin (25.3%), contact dermatitis without vesicles (13.0%) or with vesicles (9.5%). Skin irritation score was 0 (normal) in 61.0% of subjects, 0.5 (dryness or flaking) in 23.9%, 1 or 2 (erythema without or with induration) in 6.9%, and 3 or 4 (erythema with induration and vesicles/bullae) in 8.2%. Subject dropouts included 114 (14.4%) with an application site skin adverse event. Individual subject laboratory test shift to abnormal occurred for hemoglobin (3.2%), aspartate aminotransferase (6.4%), alanine aminotransferase (7.3%), and creatinine (4.2%), but few shifts (less than 0.3% per variable) were clinically significant. No increased risk of cardiovascular or cataract events was noted. This long-term study of TDiclo revealed a safety profile comparable to that shown in multiple, shorter, well-controlled, double-blind trials with the predominant adverse effect noted being an application site reaction.

Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis.

While topical non-steroidal anti-inflammatory drugs are considered safe, their long-term efficacy for osteoarthritis has been suspect. We conducted a 12-week, double-blind, double-dummy, randomized controlled trial of topical diclofenac (TDiclo) in a vehicle solution containing dimethyl sulfoxide (DMSO) in 775 subjects with radiologically confirmed, symptomatic primary osteoarthritis of the knee. This 5-arm study compared TDiclo with a placebo solution, the DMSO vehicle, oral diclofenac (ODiclo) and the combination of TDiclo+ODiclo for relieving the signs and symptoms of knee osteoarthritis. Subjects applied study solution, 40 drops four times daily, and took one study tablet daily for 12 weeks. Co-primary efficacy variables were WOMAC pain and physical function and a patient overall health assessment. Secondary variables were WOMAC stiffness and patient global assessment (PGA) of the knee osteoarthritis. TDiclo was superior to placebo for pain (-6.0 vs. -4.7, P=0.015), physical function (-15.8 vs. -12.3, P=0.034), overall health (-0.95 vs. -0.37, P<0.0001), and PGA (-1.36 vs. -1.01, P=0.016), and was superior to DMSO vehicle for all efficacy variables. No significant difference was observed between DMSO vehicle and placebo or between TDiclo and ODiclo. The commonest adverse event associated with TDiclo was dry skin (18.2%). Fewer digestive system and laboratory abnormalities were observed with TDiclo than with ODiclo. Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events. TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to, but tolerability better than ODiclo. DMSO vehicle was no more efficacious than placebo.