24 - Clinically Meaningful Results with Voltaren® Arthritis Pain (Topical Diclofenac Sodium 1%), a Non-surgical Treatment Option for Osteoarthritis of the Knee

¹Remitigate Therapeutics, Delmar, NY, USA. ²GSK Consumer Healthcare, Warren, NJ, USA

Purpose
With osteoarthritis (OA) affecting 1 in 7 adults living in the United States, it is crucial to find effective and well tolerated ways to manage pain associated with OA.^1,2 Topical nonsteroidal anti-inflammatory drugs (NSAIDs) act locally and are strongly recommended for patients with knee osteoarthritis as a pharmacologic approach to pain management.³ Further, it is recommended that topical NSAIDs be used prior to the use of oral NSAIDs to minimize systemic exposure.3 Diclofenac sodium gel 1% (DSG 1%), a topical NSAID, provided better pain relief than vehicle alone for patients with knee OA in 3 clinical trials.^4-6 A post-hoc meta-analysis of these trials was conducted to determine the percentage of patients achieving a minimal clinically important improvement (MCII) in pain and other symptoms of OA to gain insight into the clinical impact of the benefits of DSG 1% for patients. The MCII is defined as the smallest improvement in symptoms viewed as clinically meaningful for patients.7 Thus, the MCII represents an improvement of relevance in a clinical trial and the minimal meaningful change at an individual level.
Methods
All 3 studies pooled for this analysis we reconducted in US centers, and were 12-week, prospective, randomized, double-blind, multi-center, parallel group studies with similar endpoints comparing DSG 1% with vehicle in subjects with knee OA.^4-6 An MCII responder was defined as a patient who had an improvement of ≥20% relative to baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, or stiffness or in pain on movement (POM), a definition consistent with the Osteoarthritis Research Society International(OARSI)-Outcome Measures in Rheumatology(OMERACT) responder criteria.^8,9 The percentage of MCII responders was analyzed using the Cochran-Mantel-Haenszel test stratified by study. Time to MCII response was analyzed using the log-rank test stratified by study. Heterogeneity of treatment effect across studies was investigated using the Breslow-Day test.
Results
The pooled analysis included 719 DSG 1%-treated patients and 705 vehicle only-treated patients (ITT Efficacy population, N=1426). By Week 1, there was a significant difference in the number of subjects reaching MCII for all endpoints (DSG 1% vs vehicle): WOMAC pain, 67.9% vs 57.2% (P<.0001); POM, 65.8% vs 51.6% (P<.0001); WOMAC function, 58.3% vs 47.8% (P<.0001); WOMAC stiffness, 64.5% vs 53.3% (P<.0001). Mean time to first MCII was shorter with DSG 1% vs vehicle for all measures: WOMAC pain, 25.5 vs 32.2 days (P<.0001); POM, 26.6 vs 34.9 days (P<.0001); WOMAC function, 30.5 vs 38.8 days (P<.0001); WOMAC stiffness, 28.0 vs 35.2 days (P=.0001). Significant differences in the percentage of patients with an MCII between groups were still evident at Week 12 for all endpoints. No evidence of heterogeneity of treatment effect was found between studies, indicating the results from this meta-analysis were robust and reliable.
Conclusions
MCII signifies an improvement of relevance in a clinical trial by taking the patient’s perception into account. As applied to this post-hoc meta-analysis, the majority of DSG 1%-treated patients achieved clinically meaningful relief from OA pain and other symptoms within 1 week. Responses sustained over 12 weeks further suggested the clinical relevance of the meaningful patient benefits observed in the 3 original studies. Topical DSG 1%, which limits systemic NSAID exposure, was also generally well-tolerated in the original studies. It provides patients with an alternative to oral NSAIDs.^4,10

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2. US Bone and Joint Initiative. The Burden of Musculoskeletal Diseases in the United States (BMUS). https://www.boneandjointburden.org/fourth¬edition/iiib10/osteoarthritis. Accessed 6/30/20


3. Kolasinski et al. Arthritis Rheum. 2020;72(2):220-33.


4. Baraf et al. Phys Sportsmed. 2010;38(2):19-28.


5. Barthel et al. Semin Arthritis Rheum. 2009;39(3):203-12.


6. Data on File. GSK Consumer Health, Inc.


7. Kvien et al. Ann Rheum Dis. 2007;66 Suppl 3:iii40-1.


8. Tubach et al. Arthritis Care Res (Hoboken). 2012;64(11):1699-707.


9. McAlindon et al. Osteoarthritis Cartilage. 2014;22(3):363-88.


10. Kienzler, Gold, Nollevaux. J Clin Pharmacol. 2010;50(1):50-61.