Clinical meaningfulness of duloxetine's effect in Chinese patients with chronic pain due to osteoarthritis: post hoc analyses of a phase 3 randomized trial

Abstract

Purpose: To evaluate the analgesic effect of duloxetine in Chinese patients with osteoarthritis (OA) of the knee/hip at individual patient level and report the relationship between pain intensity reduction, overall improvement, and physical functioning.

Patients and methods: Post hoc analysis of 13-week, phase 3, parallel-group, randomized, placebo-controlled study of duloxetine in Chinese patients with OA pain. Patients were randomized (1:1, computer-generated, interactive web-response system) to duloxetine (60 mg once daily, n=202) or placebo (n=207). Patients, investigators, and study staff were blinded throughout the study. Duloxetine's efficacy was evaluated using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and the Osteoarthritis Research Society International and Outcome Measures in Rheumatology (OARSI-OMERACT) responder criteria. Analyses were conducted on all randomized patients with a baseline and at least one post-baseline observation.

Results: At study endpoint, the percentage of patients experiencing ≥30% pain intensity reduction (30% responders) was significantly higher in the duloxetine group than in the placebo group (63.4% vs 49.7%; P=0.008). The percentage of patients experiencing ≥50% pain intensity reduction (50% responders) in the duloxetine group was numerically higher than in the placebo group (42.8% vs 34.5%; P=0.098). Most of the 30% and 50% responders to duloxetine treatment felt either "very much improved" or "much improved" on the Patient Global Impression-Improvement at endpoint. The 30% and 50% responders to duloxetine treatment also experienced greater improvements in the Western Ontario and McMaster Universities Osteoarthritis Index physical function scores at endpoint compared with non-responders. The overall percentage of OARSI-OMERACT responders was significantly higher in the duloxetine group vs the placebo group (70.1% vs 54.9%; P=0.003).

Conclusion: Based on IMMPACT and OARSI-OMERACT criteria, the analgesic effect of duloxetine was associated with clinically relevant benefits in Chinese patients with OA of the knee/hip.

Clinicaltrialsgov identifier: NCT01931475.

Keywords: Chinese; chronic pain; clinical meaningfulness; duloxetine; efficacy; osteoarthritis.

Conflict of interest statement

Disclosure Eli Lilly and Company was involved in the study design, data collection, data analysis, and preparation of the manuscript. YW and C-NW are employees of Lilly Suzhou Pharmaceutical Co. Ltd. LY is a former employee of Lilly Suzhou Pharmaceutical Co. Ltd.; work on the manuscript was completed during tenure as a Lilly employee. VS is an employee of Eli Lilly and Company. HD is an employee of Eli Lilly de Mexico. LY and HD have stock/equity ownership in Eli Lilly and Company. SL has nothing to declare. The authors report no other conflicts of interest in this work.

Figures

Figure 1

Time course of response rate, all randomized patients. Notes: Percentage of patients achieving at least 30% pain intensity reduction (A) and percentage of patients achieving at least 50% pain intensity reduction (B). *P<0.05 comparing duloxetine with placebo. Abbreviations: Nx, number of all randomized patients with non-missing data at baseline and endpoint (baseline observation carried forward); QD, once daily.

Figure 2

Relationship between BPI and PGI: association between pain intensity reduction and overall functional improvement at study endpoint (last observation carried forward). Notes: The percentages of patients in different PGI-I categories were computed for patients experiencing <30% and ≥30% pain intensity reductions, and for patients experiencing <50% and ≥50% pain intensity reductions in the 24-hour BPI average pain, duloxetine group patients (A). Percent changes in the 24-hour BPI average pain compared with PGI-I assessment recorded at study endpoint, all randomized patients (B). Error bars represent SDs. Abbreviations: n, number of patients in the indicated category; BPI, Brief Pain Inventory; Nx, number of all randomized patients with non-missing data at baseline and endpoint (last observation carried forward); PGI-I, Patient Global Impression of Improvement; QD, once daily.

Figure 3

Improvements in WOMAC physical function from baseline to endpoint by categorical response status of pain reduction, duloxetine group patients. Notes: *P<0.001 comparing responders with non-responders (for both ≤30% pain intensity reduction and ≤50% pain intensity reduction). Error bars represent SDs. Abbreviations: n, number of patients in the indicated category; Nx, number of all randomized patients with non-missing data at baseline and endpoint (last observation carried forward); WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; QD, once daily.