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Introduction
Osteoarthritis (OA) is a highly prevalent[1-4] chronic joint disease characterized by cartilage loss, synovial inflammation and bone remodelling.[5] Occurring most frequently in the knee,[5] the prevalence of OA in this joint increases with age, from approximately 1% in people aged 25-34 years to >30% in people aged ≥75 years.[6] Radiographic evidence of knee OA is present in 37% of US adults aged ≥60 years.[7]
Signs and symptoms of OA include joint pain, stiffness, restricted motion and crepitus (creaking or crackling) on motion. OA is associated with substantial disability and diminished productivity.[1,2,8,9] A study gauging the effects of specific illnesses on functional status in the elderly determined that the four conditions most associated with disability are knee OA, heart disease, depression and stroke.[8]
NSAIDs are a recommended pharmacotherapy for pain associated with knee OA that does not respond to paracetamol (acetaminophen).[10-14] Though effective, NSAIDs have been associated with risks of gastrointestinal,[15,16] cardiovascular[17-21] and renal adverse events (AEs).[22,23] These risks increase with dose and duration of treatment and with increasing patient age.[16,21,22,24] International guidelines for osteoarthritis care recommend considering use of topical NSAIDs as an alternative to oral NSAIDs.[12,14,25] American Geriatrics Society guidelines published in 2009 recommend topical NSAIDs for pain in the elderly, noting that reduced systemic NSAID exposure with topical formulations is hoped to mitigate the risk of AEs.[26]
In 2007, diclofenac sodium 1% gel (DSG; Voltaren® Gel, Endo Pharmaceuticals Inc., Chadds Ford, PA, USA) became the first topical NSAID approved in the US for the treatment of pain associated with OA in joints amenable to topical therapy, including the knees and the hands. A pharmacokinetic study has shown that peak plasma concentrations of diclofenac were 150-fold lower in patients treated with topical DSG compared with a therapeutically equivalent dose of oral diclofenac.[27] In clinical trials, DSG has been effective in patients with OA of the knee or hands, with an incidence of gastrointestinal and other systemic AEs similar to that of vehicle.[28-30]
This post hoc analysis compares measures of safety and efficacy in patients aged ≥65 years versus 25-64 years using pooled data from three similar, randomized, placebo-controlled, clinical trials of topical DSG for knee OA.
Methods
Study Design
Safety and efficacy data were pooled from three similar 12-week, randomized, double-blind,...