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

Objective To evaluate the effectiveness and tolerability of tapentadolPR monotherapy versus tapentadolPR/ pregabalincombination 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 tapentadolPR 300 mg/day over 3 weeks. Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadolPR (500 mg/day) or tapentadolPR (300 mg/day)/ pregabalin(300 mg/day) during an 8-week comparative period. Results In the per-protocol population (n = 288), the effectiveness of tapentadolPR was clinically and statistically comparable to tapentadolPR/ pregabalinbased 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 tapentadolPR 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 somnolencewas significantly lower with tapentadolPR (16.9%) than tapentadolPR/ pregabalin(27.0%; P = 0.0302). Conclusions TapentadolPR 500 mg is associated with comparable improvements in pain intensity and quality-of-life measures to tapentadolPR 300 mg/ pregabalin300 mg, with improved central nervous system tolerability, suggesting that tapentadolPR monotherapy may offer a favorable treatment option for severe low back pain with a neuropathic component.