A Study of Topical Diclofenac for Glatiramer Acetate Injection Reactions

Background: Glatiramer acetate (GA, Copaxone™) is a daily subcutaneous treatment for multiple sclerosis (MS).  GA may cause skin and subcutaneous reactions including erythema, pain, pruritis and swelling that impact drug tolerance and adherence.  Diclofenac sodium gel (DSG) is a non-steroidal anti-inflammatory topical agent that provides local penetration with very little systemic exposure.  Thus, DSG is a potential therapeutic agent to reduce injection site reactions (ISR) to GA.

Objectives: To test the efficacy and tolerability of DSG in managing injection reactions associated with Copaxone subcutaneous injection.

Methods: Forty subjects with MS taking GA and having ISR were randomized to double-blind, crossover treatments of 2 weeks on 1% DSG and 2 weeks on matching placebo (PBO) in random order.  Regimen was 1-2gm applied topically immediately post-GA injection, repeated as needed to a maximum 4x/day (maximum daily dosage =8gm/day).  Subjects completed diaries once daily to measure injection site reactions over the past 24 hours.  The primary outcomes were: 1) Local ISR Score (LISR, a 6-item questionnaire with Yes/No responses to the presence or absence of the following:  pain, redness, warmth, swelling, bleeding, or bubble at site, with 1 point assigned to each positive response, for a maximum LISR score of 6.0); and 2) Pain score (0-10, visual analog scale).  Statistical analysis (t-test or equivalent non-parametric method) will assess mean values for the two treatment periods. 

Results: Forty subjects completed the study with no early withdrawls.  The average age = 48 years, average EDSS = 3.85, percent female = 83%, average baseline LISR score = 4.25.  

Conclusions: Final results will be presented at the Consortium meeting, including LISR score, sub-scale analyses of LISR components, pain ratings, global impression of change and adverse events. This study explores the utility of topical diclofenac gel in managing injection site reactions due to glatiramer acetate.