Maintenance of effect of duloxetine in Chinese patients with pain due to osteoarthritis: 13-week open-label extension data

Abstract

Background: The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data.

Methods: This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed.

Results: Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was - 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was - 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event.

Conclusion: The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase.

Trial registration: ClinicalTrials.gov identification number NCT01931475 . Registered 29 August 2013.

Keywords: China; Chronic pain; Duloxetine; Osteoarthritis.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by ethics review boards (ERB) covering each site, including: ERB of China-Japan Friendship Hospital; Ethics Committee of Guanghua Hospital; ERB of the Third Xiangya Hospital of Central South University; ERB of Anhui Provincial Hospital; Shanghai Changhai Hospital Ethics Committee; ERB of Jilin University China-Japan Union Hospital; Clinical Medical Ethics Committee of the First Affiliated Hospital of Bengbu Medical College; ERB of the Second Xiangya Hospital of Central South University; ERB of the First Affiliated Hospital of Anhui Medical University; ERB of Tianjin Medical University General Hospital; ERB of West China Hospital of Sichuan University; ERB of the General Hospital of Shenyang Military Region; ERB of the First Affiliated Hospital of Jinan University; ERB of Nanfang Hospital; ERB of Pingxiang People’s Hospital; and ERB of Zhuzhou Central Hospital.

Written informed consent was obtained from all patients before participation in the study.

Consent for publication

Not applicable.

Competing interests

GW, LB, XL, ZL, DZ, JC, and DH have no conflicts of interest to report. HD, LY, CW, TW, and VS are or were employees and minor shareholders of Eli Lilly and Company.

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Figures

Fig. 1

Patient disposition. Abbreviations: DLX_DLX = patients who received duloxetine during both the placebo-controlled and the extension phases; PLA_DLX = patients who received placebo during the placebo-controlled phase and duloxetine during the extension phase

Fig. 2

Least-squares mean change in BPI average pain rating for patients who entered the extension phase. Mixed-model repeated measures analysis. Abbreviations: BPI = Brief Pain Inventory; DLX = duloxetine; PLA = placebo

Fig. 3

Response rates at the end of the extension phase. The response rates were based on the change from baseline of the placebo-controlled phase to endpoint (last observation carried forward) in Brief Pain Inventory average pain rating. Abbreviations: DLX = duloxetine; PLA = placebo