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

Abstract

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.

Intra-articular lornoxicam loaded PLGA microspheres: enhanced therapeutic efficiency and decreased systemic toxicity in the treatment of osteoarthritis

“…The local drug concentration after oral administration is low and the gastrointestinal toxic and side effect are serious (Matsuno et al 2009;Simon et al 2009), while surgery for treatment of OA has shortcomings including high cost, limited efficacy and poor patient compliance (Moseley et al 2002;Rat et al 2010). Moreover, the absorption of transdermal preparations is poor and local skin irritation is inevitable.…”

Tolerability of diclofenac sodium 1% gel with concomitant medications known to interact with diclofenac

“…9 Similarly, numerous other studies of topical NSAIDs have reported effective relief of OA pain with low rates of dose-related gastrointestinal, cardiovascular, renal, and other systemic AEs; the frequency of these AEs has typically been higher in studies of oral NSAIDs. [7][8][9]17,18 A limitation of this study is that the sample size was not large enough to allow for an analysis of AEs in patients with DDIs based on age and other demographic variables. However, a pooled analysis of 3 trials in which 721 patients with OA of the knees were treated with DSG found no difference in efficacy and similarly low AE rates in patients aged , 65 years versus those aged $ 65 years.…”

Managing osetoarthritis

“…28 Multiple formulations have been trialled including topical ketoprofen 29 and diclofenac sodium 1.5% topical solution in dimethyl sulfoxide. 27 Safety with diclofenac sodium 1% gel has also been shown in the older population in a 12-month, post hoc analysis of patients with knee osteoarthritis. The overall rates of cardiovascular and gastrointestinal adverse events were similar for people under and over 65 years of age.…”

“…27,28 Efficacy is greater than placebo and comparable to oral NSAIDs. 28 Multiple formulations have been trialled including topical ketoprofen 29 and diclofenac sodium 1.5% topical solution in dimethyl sulfoxide.…”