Enomoto, Hiroyuki Biomedicine, Medicines Development Unit, Eli Lilly Japan K.K., Kobe, Japan
Ishida, Mitsuhiro Clinical Research Development, Shionogi & Co. Ltd, Osaka, Japan
Tsuji, Toshinaga Medical Affairs Department, Shionogi & Co. Ltd, Osaka, Japan
Ochiai, Toshimitsu Biostatistics Center, Shionogi & Co. Ltd, Osaka, Japan
Konno, Shinichi Department of Orthopaedic Surgery, Fukushima Medical University, Fukushima, Japan
Purpose: To assess long-term safety, tolerability, and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis.
Methods: In this open-label extension study (NCT02335346), Japanese patients with kneeosteoarthritis and pain (Brief Pain Inventory [BPI] – Severity average pain score ≥4 at start of randomized trial) who had previously received duloxetine 60 mg/day or placebo for 14 weeks in a double-blind randomized trial entered the extension and received duloxetine 60 mg/day for 48 weeks. The primary outcome was safety/tolerability, secondary outcomes were change in BPI-Severity (BPI-S) average pain, BPI-Interference (BPI-I), Patient Global Impression-Improvement (PGI-I), Clinical Global Impression-Improvement (CGI-I), 36-item Short-Form Health Survey (SF36), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and exploratory outcomes were knee range of motion (efficacy outcome) and Kellgren–Lawrence grade (safety outcome).
Results: Of 323 patients who completed the randomized trial, 93 (50 placebo, 43 duloxetine) entered the extension. Most patients (85, 91.4%) experienced an adverse event, most commonly constipation, nasopharyngitis, somnolence, and dry mouth (≥10% of patients). There were eight serious adverse events in seven patients and no deaths. No obvious duloxetine-related changes were observed in laboratory tests, vital signs, or electrocardiograms. The change from baseline in BPI-S average pain score was significant throughout the extension. Significant reductions in BPI-I, PGI-I, CGI-I, WOMAC, and SF36 scores were also maintained through 52 weeks. There were no substantial changes in range of motion or Kellgren–Lawrence grade.
Conclusion: In Japanese patients with chronic knee pain due to osteoarthritis, long-term treatment with duloxetine was well tolerated and associated with sustained improvements in pain and health-related quality of life without radiographic deterioration.
chronic pain due to knee osteoarthritis
quality of life
Western Ontario and McMaster Universities Osteoarthritis Index
Journal of Pain Research
Dove Press Ltd
Faculty of Medicine