Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study
Received 17 April 2018
Accepted for publication 7 June 2018
Published 31 July 2018 Volume 2018:11 Pages 1391—1403
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Michael E Schatman
Yuji Uchio,1 Hiroyuki Enomoto,2 Mitsuhiro Ishida,3 Toshinaga Tsuji,4 Toshimitsu Ochiai,5 Shinichi Konno6
1Department of Orthopaedic Surgery, Shimane University School of Medicine, Shimane, Japan; 2Bio-medicine, Medicines Development Unit, Eli Lilly Japan K.K., Kobe, Japan; 3Clinical Research Development, Shionogi & Co. Ltd, Osaka, Japan; 4Medical Affairs Department, Shionogi & Co. Ltd, Osaka, Japan; 5Biostatistics Center, Shionogi & Co. Ltd, Osaka, Japan; 6Department 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 knee osteoarthritis 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.
Keywords: analgesics, chronic pain due to knee osteoarthritis, duloxetine, quality of life, Western Ontario and McMaster Universities Osteoarthritis Index
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