Pooled safety analysis of diclofenac sodium topical solution 1.5% (w/w) in the treatment of osteoarthritis in patients aged 75 years or older

Abstract

Background

This study aimed to determine the safety of diclofenac sodium topical solution 1.5% (w/w) in 45.5% dimethyl sulfoxide (TDiclo) for the treatment of knee or hand osteoarthritis in persons aged 75 years or older.

Methods

A pooled analysis of safety data from seven multicenter, randomized, blinded, Phase III clinical trials (4–12 weeks’ duration) of TDiclo was conducted. The analysis focused on a subset of patients (n = 280) aged 75 years or older with a primary diagnosis of osteoarthritis of the knee (six trials) or hand (one trial). Patients received one of three topical treatments: TDiclo (n = 138); placebo (2.33% or 4.55% dimethyl sulfoxide, n = 39); or control (45.5% dimethyl sulfoxide, n = 103). Treatment groups were compared using Chi-square analysis, Fisher’s Exact test, or analysis of variance.

Results

The most common adverse events involved the skin or subcutaneous tissue, primarily at the application site. The incidence of dry skin was higher in the TDiclo (36.2%; P < 0.0001) and dimethyl sulfoxide control (18.4%; P = 0.0142) groups than in the placebo group (2.6%); the incidence of other skin or subcutaneous tissue adverse events was similar between the groups. Relatively few patients (<18%) experienced gastrointestinal adverse events, and group differences were not detected. In the TDiclo group, constipation (3.6%), diarrhea (3.6%), and nausea (3.6%) were the most common gastrointestinal adverse events. Cardiovascular and renal/ urinary adverse events were rare, and group differences were not detected. There was one case (0.7%) each of hypertension, spider veins, and vasodilation in the TDiclo group. Changes from baseline to the final visit in blood pressure and hepatic/renal enzyme levels were also similar between the groups.

Conclusion

TDiclo appears to be well tolerated for the treatment of osteoarthritis in persons aged 75 years or older.

Keywords:

• adverse events
• analgesic
• arthritis
• gastrointestinal
• nonsteroidal anti-inflammatory drugs
• tolerability

Disclosure

SHR has served as a consultant/advisory board member and speaker for Covidien. He holds stock in Transdel Pharmaceuticals. PF is an employee of Mallinckrodt Inc, which sponsored the study and the preparation of this manuscript. Technical editorial and writing support for the preparation of this manuscript was provided by Karamarie Fecho, Synchrony Medical, LLC, West Chester, PA.