Efficacy and Safety of Duloxetine on Osteoarthritis Knee Pain: A Meta-Analysis of Randomized Controlled Trials.

Objectives: The aim of this meta-analysis was to evaluate the efficacy and safety of duloxetine for management of osteoarthritis knee (OAK) pain.

Methods: A systematic literature search of articles for management of OAK using duloxetine were performed in PubMed, EBSCO, EMBASE, ScienceDirect, MEDLINE, ClinicalTrials.gov, Google Scholar, and Cochrane Central Register of Controlled Trials from the available date of inception until the latest issue (October 2013). Potentially relevant randomized controlled trials (RCTs) regarding to comparison of efficacy and safety of duloxetine with placebo for managing OAK pain were included. Also, studies with specific data regarding to pain reductions and response rate, Patient Global Impression of Improvement (PGI-I), functional improvement, Western Ontario and McMaster Osteoarthritis Index (WOMAC), adverse events (AEs), treatment-emergent AEs (TEAEs), mortality were included and analyzed, and those with confounding conditions were excluded. Studies were assessed for quality using the Jadad five-point score for RCTs. Finally, a meta-analysis of all RCTs eligible for inclusion criteria was performed using Review Manager 5.1 meta-analysis software.

Results: Three RCTs that enrolled 1,011 patients were included in our meta-analysis. There were statistically significant differences between patients taking duloxetine and those taking placebo with regard to the reductions in pain intensity (992 patients, mean difference [MD] = -0.88, 95% confidence interval [CI] -1.11--0.65, P < 0.0001), a moderate improvement in pain intensity (>= 30% response rate; 989 patients, risk ratio [RR] = 1.49, 95% CI 1.31-1.70, P < 0.0001), a substantial improvement in pain intensity (>=50% response rate; 989 patients, RR = 1.69, 95% CI 1.27-2.25, P = 0.0004). Statistically significant differences in PGI-I (976 patients, MD = -0.47, 95% CI -0.63 to -0.30, P < 0.0001) and WOMAC-physical function subscale (977 patients, MD = -4.25, 95% CI -5.82 to -2.68, P < 0.0001) were observed. Similarly, more AEs, TEAEs, and discontinuations for any reason were associated with the use of duloxetine than with placebo (1,011 patients, RR = 2.15, 95% CI 1.48-3.11, P < 0.0001; 1,011 patients, RR = 1.32, 95% CI 1.16-1.49, P < 0.0001; 1,011 patients, RR = 1.43, 95% CI 1.14-1.78, P = 0.002, respectively). However, differences in serious AEs were not significantly statistically different. Moreover, no deaths occurred during these three studies.

Conclusion: This analysis suggests duloxetine (60/120 mg quaque die (QD)), compared with placebo control, resulted in a greater reduction in pain, improved function and patient-rated impression of improvement, and acceptable adverse effects for the treatment of OAK pain after approximately 10-13 weeks of treatment.