Duloxetine 60 mg for chronic low back pain: post hoc responder analysis of double-blind, placebo-controlled trials

Abstract

Introduction: Duloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP.

Patients and methods: This was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12-14 weeks) in adult patients with CLBP. Primary outcome was proportion of patients with ≥30% reduction in Brief Pain Inventory (BPI) average pain ("pain reduction") at 12-14 weeks. The proportion of patients with ≥30% and ≥50% (secondary outcome) pain reduction in duloxetine and placebo groups was compared. Variables for responder analyses were early improvement (≥15% pain reduction at Week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites according to the Michigan Body Map (≥2 vs 1 [isolated CLBP]; 1 trial); relative risk (RR) and 95% confidence interval (CI) were calculated.

Results: Compared with placebo (n = 653), a greater proportion of duloxetine-treated patients (n = 642) achieved ≥30% (59.7% vs 47.8%; P < 0.001) and ≥50% pain reduction (48.6% vs 35.1%; P < 0.001). Among duloxetine-treated patients, early improvement was associated with greater likelihood of ≥30% (RR [95% CI], 2.91 [2.30-3.67]) or ≥50% (3.24 [2.44-4.31]) pain reduction. Women were slightly more likely than men to achieve ≥30% (RR [95% CI], 1.14 [1.00-1.30]) or ≥50% (1.17 [0.99-1.38]) pain reduction. Response rates were similar between age, CLBP duration, and baseline BPI average pain score subgroups. Patients with ≥2 painful sites were more likely to respond to duloxetine 60 mg relative to placebo than patients with isolated CLBP (RR, duloxetine vs placebo [95% CI]: ≥30% reduction, ≥2 painful sites 1.40 [1.18-1.66], isolated CLBP 1.07 [0.78-1.48]; ≥50% reduction, ≥2 painful sites 1.51 [1.20-1.89], isolated CLBP 1.23 [0.81-1.88]).

Conclusion: Early pain reduction was indicative of overall response. Patients with multiple painful sites had more benefit from duloxetine than patients with isolated CLBP.

Keywords: Brief Pain Inventory; Michigan Body Map; SNRI; chronic pain; low back pain; multiple painful sites.

Figure 1

Proportion of patients with CLBP who achieved ≥30% or ≥50% reduction in BPI Severity average pain after 12–14 weeks treatment with duloxetine 60 mg (black bars; n = 642) or placebo (white bars; n = 653). Abbreviations: BPI, Brief Pain Inventory; CLBP, chronic low back pain.

Figure 2

(A, B) Responder analysis (A, ≥30% reduction in BPI average pain; B, ≥50% reduction in BPI average pain) for patients with CLBP treated with duloxetine 60 mg for 12–14 weeks. Notes: Response rates and RR (95% CI) are shown for the following factors: early improvement, defined as ≥15% reduction in BPI average pain at Week 2 (yes vs no); number of painful body sites according to the MBM (≥2 vs 1; Japanese trial only14); sex (F vs M); age (<65 y vs ≥65 y); CLBP duration (<5 years vs ≥5 years); and baseline BPI average pain score (≥6 vs <6). Abbreviations: BPI, Brief Pain Inventory; CI, confidence interval; CLBP, chronic low back pain; F, female; M, male; MBM, Michigan Body Map; RR, relative risk; y, years.

Figure 3

(A, B) Effect of the number of painful body sites (according to the MBM) on the RR (duloxetine 60 mg vs placebo) of achieving ≥30% reduction (A) or ≥50% reduction (B) in BPI average pain in patients with 1 (isolated CLBP), ≥2, 2, 3, 4, or ≥5 painful sites. Abbreviations: BPI, Brief Pain Inventory; CI, confidence interval; CLBP, chronic low back pain; DLX, duloxetine 60 mg; MBM, Michigan Body Map; PLC, placebo; RR, relative risk.