Diclofenac Diethylamine 2.32% Gel Noninferior to 1.16% Gel for Ankle Sprain Pain

Among patients with ankle sprain, diclofenac diethylamine (DDEA) 2.32% gel applied twice daily had similar outcomes as DDEA 1.16% gel applied 4 times daily, according to the results of a randomized, double-blind, noninferiority study published in BMC Musculoskeletal Disorders.

This study was conducted at 15 sites in China between 2019 and 2020. Patients (N=302) with grades 1 or 2 ankle sprain and pain on movement scores 50 mm or greater on a 100-mm visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive DDEA 2.32% gel twice daily with a twice-daily placebo gel (n=150) or DDEA 1.16% gel 4 times daily (n=152). The primary outcome was pain on movement on day 5, and the noninferiority margin was defined as a VAS score of 13 mm.

The mean age of study participants was 34 years. Grade 1 ankle sprain was reported by 62.7% and 63.8% of participants in the DDEA 2.32% and DDEA 1.16% gel arms, respectively, with mean pain on movement scores reported as 68.5 (SD, 10.7) and 67.2 (SD, 9.7) mm.

Change in pain on movement scores from baseline to day 5 were -42.8 mm among the DDEA 2.32% gel recipients compared with -43.1 mm among the DDEA 1.16% gel recipients. The least-squares mean difference (LSMD) in pain on movement scores was 1.11 mm (P =.595), which was within the noninferiority margin.

No significant group differences were observed on days 3, 5, and 8 for the secondary outcomes of tenderness as measured by algometry, ankle joint function measured with Karlsson scoring, and swelling using the Figure of Eight method. At day 5, no group difference in patient diary sum of pain intensity over a 12-hour interval after first dose was reported (LSMD, -0.50; 95% CI, -1.91 to 0.92; P =.492).

In the DDEA 2.32% gel treatment arm, 11 patients reported 13 adverse events, and in the DDEA 1.16% gel treatment arm, 12 patients reported 13 adverse events. Treatment-emergent adverse events included allergic dermatitis (n=2), skin exfoliation (n=2), application site inflammation (n=1), and arthralgia (n=1).

A major limitation of this study was its lack of a placebo comparator.

These data indicate that for pain associated with ankle sprain, DDEA 2.32% gel applied twice a day could be a viable treatment alternative to DDEA 1.16% gel applied 4 times a day. The study authors state, “In a real-world setting, the added convenience of BID versus QID administration should increase treatment adherence, resulting in better efficacy and patient satisfaction.”

Disclosure: This study was sponsored by GSK Consumer Healthcare. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies, including consulting for and employment at GSK Consumer Healthcare. Please see the original reference for a full list of authors’ disclosures.