Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial

Abstract

Objective:

To determine the efficacy, tolerability, and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteoarthritis (OA) of the knee with pain of moderate or greater severity.

Research design and methods:

This was a 10-week randomized, double-blind, flexible-dose (duloxetine 60/120 mg/day), placebo-controlled trial that enrolled adult outpatients who had persistent moderate pain (≥4 on a 0–10 numerical rating scale) due to OA of the knee, despite, per protocol, having received optimized oral NSAID therapy (specific drug, dose, and frequency at investigator discretion).

Clinical trials registration:

Trial registration: ClinicalTrials.gov identifier: NCT01018680.

Main outcome measure:

Patients entered daily pain ratings in a telephone-based diary. The primary efficacy outcome was the weekly mean of the daily average pain rating at week 8. Safety outcomes were assessed during the entire 10-week study.

Results:

A total of 524 patients randomly received duloxetine 60/120 mg/day (N = 264) or placebo (N = 260). In total, 74% of the patients completed the study. Mean age was 61 years (SD 9.2), 57% were female, and 81% were white. Duloxetine-treated patients had significantly greater pain reduction at week 8 (p < 0.001) than placebo-treated patients. In addition, relative to placebo at week 8, duloxetine-treated patients had significant improvements in physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (p < 0.001), and Patient Global Impression of Improvement (p < 0.001). Compared to placebo, significantly more nausea, dry mouth, constipation, fatigue and decreased appetite were reported by patients taking duloxetine (each p < 0.05). Discontinuation due to adverse events occurred more commonly in the duloxetine group than the placebo group (p = 0.03).

Conclusion:

Duloxetine added to oral NSAID therapy provided additional significant pain reduction, improved function, and patient-rated impression of improvement. Adverse events were consistent with those seen in previous duloxetine trials. The short duration of the study may not reflect the longer term efficacy and safety of NSAID/duloxetine cotherapy.

Keywords::

• Duloxetine
• Efficacy
• Function
• NSAIDs
• Osteoarthritis
• Pain
• Safety

Transparency

Declaration of funding

Financial support was provided by Eli Lilly and Company, Indianapolis, IN, USA. Employees of Lilly were involved in the study design, analysis of data, critical revision of the manuscript, and in the decision to submit the manuscript for publication.

Declaration of financial/other relationships

At the time this manuscript was written, E.P.F., R.C.R., and M.M.W. were full-time employees of Eli Lilly and/or one of its subsidiaries and were minor stockholders of Eli Lilly and Company. M.C.H. currently receives research support from the National Institutes of Health; is a consultant for Abbott Laboratories, Amgen, Astra-Zeneca Pharmaceutical Co., Bioiberica S.A., Bristol Myers Squibb Company, Covidien, Eli Lilly and Company, EMD Serono, Inc., Genentech/Roche, Iroko Pharmaceuticals, Merck & Co. Inc., NiCox S.A., Pfizer Inc., Pozen Inc., Rand Corporation, Smith & Nephew, TransPharma Medical Ltd, and UCB Inc.; is a member or chair of DSMB, National Eye Institute, Novartis Pharma A.G., Savient Pharmaceuticals Inc., and Stryker Biotech LLC; and is a member of the medical advisory board and owns stock in Theralogixx, LLC. TDB is a full-time employee of i3 Data Services, a division of InVentiv Health Company. She was contracted by Eli Lilly for writing services.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors wish to thank all of the participating investigators and patients for their contributions to this study. Appreciation is expressed to Angela Lorio for editorial contributions. Ms Lorio is a scientific editor employed full-time by i3 Statprobe, part of the InVentiv Health Company. Eli Lilly and Company contracted the technical writing of this manuscript with i3 Statprobe. Also acknowledged are: Vladimir Skljarevski, MD; Peng Liu, PhD; Deborah D’Souza MD, PhD; and Barbara McLean for critical review of this manuscript.