A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis

Abstract

PurposeTo examine the efficacy and safety of duloxetine in Japanese patients with knee pain due to osteoarthritis.Patients and methodsPatients were randomized to receive duloxetine 60 mg/day or placebo for 14 weeks in a double-blind manner (ClinicalTrials.gov Identifier: NCT02248480). The primary efficacy endpoint was mean change in Brief Pain Inventory pain severity (BPI-Severity) average pain. Secondary endpoints included improvement in other BPI-Severity scales, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, health-related quality of life (HRQoL) scales, range of motion of the knee joint, safety and tolerability, and structural changes on X-ray images.ResultsOf the 354 randomized patients, 161 in the duloxetine group and 162 in the placebo group completed the study. BPI-Severity average pain improved significantly with duloxetine vs. placebo (−2.57 vs. −1.80; adjusted mean difference: −0.77; 95% CI: −1.11 to −0.43; P<0.0001). Secondary efficacy endpoints and most HRQoL scales showed greater improvements in the duloxetine group than the placebo group. Adverse events observed in ≥5% of patients that were more frequent in the duloxetine than placebo group were somnolence, constipation, dry mouth, nausea, malaise, and decreased appetite. There were no marked changes in range of motion of the knee joint (efficacy), X-ray images, or Kellgren–Lawrence grade (safety) in either group.ConclusionDuloxetine reduced pain and improved function in patients with knee osteoarthritis, without causing X-ray abnormalities or altered knee joint mobility. Reduced pain was associated with improved HRQoL. Adverse events were consistent with duloxetine’s known safety profile.

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

“…In addition, duloxetine improved the sensitivity to non‐noxious mechanical stimuli measured by a pain behavioral test in the intervertebral disc‐related radiculopathy model in rats, which is truly regarded as a model for neuropathic pain . With regard to clinical results, several studies conducted in the United States, Europe, and Asia have shown significant improvements in pain, joint junction and function, and health‐related quality of life for patients with hip or knee OA who were treated with duloxetine compared with placebo without serious adverse events . Because duloxetine has been already recommended as the first‐line drug for neuropathic pain based on strong GRADE recommendations for use, our hypothesis that duloxetine is effective for neuropathic pain in OA can be considered reasonable.…”

“…The Osteoarthritis Research Society International (OARSI) guidelines recommend duloxetine as treatment for multiple‐joint OA with or without comorbidities . Some RCTs and meta‐analyses revealed the efficacy and safety of duloxetine for OA pain . Moreover, the SNRIs, including duloxetine, are regarded as the first therapeutic agents for neuropathic pain .…”

Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta‐analysis of randomised controlled trials

“…With regard to randomisation and allocation concealment, one study 23 showed an unclear risk and the remaining five studies [20][21][22]24,25 all showed a low risk. Furthermore, all six studies appeared to be at low risk with regard to blindness, incomplete outcome data, and selective reporting, but they were unclear for other biases.…”

Osteoarthritis: epidemiology, classification, risk factors, and progression, clinical presentation, diagnosis, and treatment

“…В рандомизированном двойном слепом плацебо-контролируемом исследовании японских ученых оценивались эффективность и безопасность дулоксетина у пациентов с ОА коленных суставов в течение 14 нед. Показано значимое уменьшение боли, скованности, функциональной недостаточности и улучшение качества жизни в группе дулоксетина [34].…”