Back to Journals » Journal of Pain Research » Volume 11

Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study

Authors Uchio Y, Enomoto H, Ishida M, Tsuji T, Ochiai T, Konno S

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 anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Michael 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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]