Effectiveness and Safety of Tapentadol Prolonged Release (<scp>PR</scp>) Versus a Combination of Tapentadol <scp>PR</scp> and Pregabalin for the Management of Severe, Chronic Low Back Pain With a Neuropathic Component: A Randomized, Double‐blind, Phase 3b Study

Abstract

OBJECTIVE: To evaluate the effectiveness and tolerability of tapentadol PR monotherapy versus tapentadol PR/pregabalin combination therapy for severe, chronic low back pain with a neuropathic component. METHODS: Eligible patients had painDETECT "unclear" or "positive" ratings and average pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) at baseline. Patients were titrated to tapentadol PR 300 mg/day over 3 weeks. Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadol PR (500 mg/day) or tapentadol PR (300 mg/day)/pregabalin (300 mg/day) during an 8-week comparative period. RESULTS: In the per-protocol population (n = 288), the effectiveness of tapentadol PR was clinically and statistically comparable to tapentadol PR/pregabalin based on the change in pain intensity from randomization to final evaluation (LOCF; LSMD [95% CI], -0.066 [-0.57, 0.43]; P < 0.0001 for noninferiority). Neuropathic pain and quality-of-life measures improved significantly in both groups. Tolerability was good in both groups, in line with prior trials in the high dose range of 500 mg/day for tapentadol PR monotherapy, and favorable compared with historical combination trials of strong opioids and anticonvulsants for combination therapy. The incidence of the composite of dizziness and/or somnolence was significantly lower with tapentadol PR (16.9%) than tapentadol PR/pregabalin (27.0%; P = 0.0302). CONCLUSIONS: Tapentadol PR 500 mg is associated with comparable improvements in pain intensity and quality-of-life measures to tapentadol PR 300 mg/pregabalin 300 mg, with improved central nervous system tolerability, suggesting that tapentadol PR monotherapy may offer a favorable treatment option for severe low back pain with a neuropathic component.