Background/Purpose: Topical agents are recommended for the initial treatment of patients with knee osteoarthritis (OA). Diclofenac sodium gel 1% (DSG 1%), a topical nonsteroidal anti-inflammatory drug (NSAID), demonstrated significant improvements in the signs and symptoms of knee OA and a higher percentage of patients meeting the Osteoarthritis Research Society International criteria for a response relative to a vehicle placebo in a trial of patients with OA of the knee. This post-hoc analysis was conducted to determine the percentage of patients in this study achieving a minimal clinically important improvement (MCII, the smallest improvement considered meaningful by an individual patient) in OA signs and symptoms.   

Methods: This study was a 12-week, prospective, randomized, double-blind, multicenter, parallel group study that compared DSG 1% with placebo in subjects with OA of the knee. MCII responders were defined as having an improvement of ≥20% over baseline in Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) pain, function, and stiffness and in pain on movement (POM) per the definition used by Tubach F et al. (Arthritis Care Res (Hoboken). 2012;64(11):1699-707). The percentage of responders was analyzed using logistic regression with treatment and stratification factors (number of knees treated and Kellgren-Lawrence grade) included in the model. Time to MCII response was analyzed using the log-rank test with the same stratification factors.

Results: This analysis included 207 DSG 1%-treated and 212 vehicle-treated patients. Significant differences in the percentage of patients reaching an MCII were evident at Week 1 (DSG 1% vs vehicle, odds ratio [95% confidence limits]): WOMAC pain, 74.9% vs 61.8%, OR 1.87 [1.23, 2.85], P=.004; POM, 71.5% vs 59.9%, OR 1.71 [1.13, 2.59], P=.011; WOMAC function, 69.6% vs 58%, OR 1.70 [1.13, 2.56], P=.011; WOMAC stiffness, 75.4% vs 64.6%, OR 1.70 [1.11, 2.60], P=.015. Time to first MCII response was lower with DSG 1% for all measures: WOMAC pain, P=.001; POM, P=.013; WOMAC function, P=.018; WOMAC stiffness, P=.01. Significant differences in responder rates between groups were evident at most subsequent time points, with a higher percentage of patients with an MCII response with DSG 1% at Week 12 for all endpoints.

Conclusion: The MCII, a metric that considers patient perspectives on clinical improvements, was applied to data from a published clinical trial first time. In this analysis, most patients treated with DSG 1% achieved clinically meaningful relief within 1 week that was sustained for ≥12 weeks. Despite a relatively high vehicle response rate, a significantly higher percentage of patients had MCII responses with DSG 1%.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinically-relevant-improvements-in-knee-osteoarthritis-pain-with-diclofenac-sodium-gel-1/