Safety and efficacy of duloxetine treatment in older and younger patients with osteoarthritis knee pain: a post hoc, subgroup analysis of two randomized, placebo-controlled trials

BACKGROUND: Osteoarthritis (OA) knee pain is common in older patients and contributes to decreased quality of life. Older patients are generally at higher risk of adverse drug reactions due to age-related changes in physiology that affect drug disposition, metabolism, and response. These analyses examined efficacy and safety outcomes of older (≥65 years) versus younger patients from clinical trials of duloxetine in the management of OA knee pain. METHODS: This is a post hoc analysis of two 13-week studies, in which patients were randomized to duloxetine 60 mg/day or placebo. Both studies allowed potential dose changes after 7 weeks of dosing, with Study I re-randomizing duloxetine treated patients to either stay on 60 mg/day or increase to 120 mg/day; while Study II more closely mimicked clinical practice by escalating only non-responding patients to 120 mg/day. For all analyses patients were subgrouped by age: older (≥65 years) and younger (40–64 years). Overall efficacy and safety age-group comparisons of duloxetine versus placebo were performed using pooled data from both studies with all duloxetine dose levels combined. Safety analyses included discontinuation rates, treatment-emergent adverse events, and serious adverse events. To evaluate the effects of increasing the dose in non-responding patients, only Study II data were evaluated. Treatment arms were defined post hoc as placebo, duloxetine 60 mg/day, and duloxetine 60/120 mg/day. RESULTS: At study end, patients in each age group who were treated with duloxetine versus placebo had significantly greater improvement in pain (both, p<.05), and there was no significant effect of age on treatment (p=.72). Increasing the dose to 120 mg in non-responding patients was not found to have a significant advantage. Among treatment-emergent adverse events with duloxetine treatment, only dizziness had a significantly differential treatment effect (p=.02) with greater incidence over placebo in younger patients (6.6% versus 0.6%, p=.02), but not in older patients (1.0% versus 3.2%, p=.29). CONCLUSIONS: Duloxetine was efficacious and generally well tolerated for management of symptomatic knee OA in both older and younger patients, but increasing the dose to 120 mg in non-responding patients did not provide additional benefit.