Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study

Abstract

Purpose: Duloxetine is efficacious for chronic low back pain (CLBP). This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919) assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation) have enhanced responses to duloxetine.

Patients and methods: Patients (N = 456) with CLBP for ≥6 months and Brief Pain Inventory (BPI) average pain severity score of ≥4 were randomized (1:1) to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction). Subgroup analyses included early pain reduction (≥30%, 10%-30%, or <10% at Week 4) and early TR-AESIs (with or without TR-AESIs by Week 2). Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL), and response rate (≥30% or ≥50% pain reduction at Week 14).

Results: Patients with ≥30% early pain reduction (n = 108) or early TR-AESIs (n = 50) had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226), whereas patients with 10%-30% (n = 63) or <10% (n = 48) pain reduction did not; patients without early TR-AESIs (n = 180) had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction) were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%-30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.

Conclusion: Early pain reduction or TR-AESIs may predict which CLBP patients are most likely to respond to duloxetine with improvements in pain and QOL.

Keywords: Brief Pain Inventory; adverse events; duloxetine; low back pain; quality of life; responder.

Conflict of interest statement

Disclosure TT, NI, MI, and TO are employees and minor stock holders of Shionogi & Co. Ltd. SK has received consulting fees and honoraria from Eli Lilly Japan K.K. and Shionogi & Co. Ltd, and has received research grants from Shionogi & Co. Ltd. The authors report no other conflicts of interest in this work.

Figures

Figure 1

Least squares mean (95% confidence interval) change from baseline in Brief Pain Inventory average pain severity score through Week 14 in patients with chronic low back pain treated with duloxetine 60 mg/day or placebo (white squares; n = 226). Notes: Duloxetine subgroups were patients who had ≥30% (black circles; n = 108), 10%–30% (gray circles; n = 63), or <10% pain reduction (white circles; n = 48) at Week 4. Mean (standard deviation) Brief Pain Inventory average pain severity scores at baseline were 5.2 (1.1), 5.2 (1.1), 5.0 (1.1), and 5.1 (1.0) for the ≥30% pain reduction, 10%–30% pain reduction, <10% pain reduction, and placebo groups, respectively. ***P ≤ 0.001 and ****P ≤ 0.0001 compared with placebo. Abbreviations: CI, confidence interval; LS, least squares.

Figure 2

Proportion of patients with chronic low back pain who achieved (A) ≥30% or (B) ≥50% pain reduction after 14 weeks of duloxetine 60 mg/day treatment (black bars) among those with ≥30% (n = 108), 10%–30% (n = 63), or <10% pain reduction (n = 48) at Week 4, and among those receiving placebo (white bar; n = 226). Note: *P < 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001 compared with placebo.

Figure 3

Least squares mean (95% confidence interval) change from baseline in Brief Pain Inventory Interference quality-of-life domains through Week 14 in patients with chronic low back pain treated with duloxetine 60 mg/day or placebo (white squares; n = 226). Notes: Duloxetine subgroups were patients who had ≥30% (black circles; n = 108), 10%–30% (gray circles; n = 63), or <10% pain reduction (white circles; n = 48) at Week 4. Brief Pain Inventory Interference domains included (B) general activity, (C) mood, (D) walking ability, (E) normal work, (F) relationships with others, (G) sleep, and (H) enjoyment of life, as well as (A) the average of the 7 domains. *P < 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001 compared with placebo. Abbreviations: CI, confidence interval; LS, least squares.

Figure 4

Adverse events of special interest ([A] nausea, [B] somnolence, [C] constipation) in patients with chronic low back pain treated with duloxetine 60 mg/day for 14 weeks (n = 230). Note: Adverse events are shown according to the time to onset and the duration.

Figure 5

Least squares mean (95% confidence interval) change from baseline in Brief Pain Inventory average pain severity score through Week 14 in patients with chronic low back pain treated with duloxetine 60 mg/day or placebo (white squares; n = 226). Notes: Duloxetine subgroups were patients who did (black circles; n = 50) or did not (gray circles; n = 180) have an adverse event of special interest (nausea, somnolence, constipation) between baseline and Week 2. Mean (standard deviation) Brief Pain Inventory average pain severity scores at baseline were 5.2 (1.1), 5.1 (1.1), and 5.1 (1.0) for the early adverse event, no early adverse event, and placebo groups, respectively. *P < 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001 compared with placebo. Abbreviations: CI, confidence interval; LS, least squares.

Figure 6

Proportion of patients with chronic low back pain who achieved (A) ≥30% or (B) ≥50% pain reduction after 14 weeks of duloxetine 60 mg/day treatment (black bars) among those with (n = 50) or without (n = 180) adverse events of special interest between baseline and Week 2, and among those receiving placebo (white bar; n = 226). Note: **P ≤ 0.01 compared with placebo. Abbreviation: AESIs, adverse events of special interest.

Figure 7

Least squares mean (95% confidence interval) change from baseline in Brief Pain Inventory Interference quality-of-life domains through Week 14 in patients with chronic low back pain treated with duloxetine 60 mg/day or placebo (white squares; n = 226). Notes: Duloxetine subgroups were patients who did (black circles; n = 50) or did not (gray circles; n = 180) have an adverse event of special interest between baseline and Week 2. Brief Pain Inventory Interference domains included (B) general activity, (C) mood, (D) walking ability, (E) normal work, (F) relationships with others, (G) sleep, and (H) enjoyment of life, as well as (A) the average of the 7 domains. *P < 0.05, **P ≤ 0.01, and ***P ≤ 0.001 compared with placebo. Abbreviations: CI, confidence interval; LS, least squares.