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

ObjectiveTo 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. MethodsEligible 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 300mg/day over 3weeks. Patients with 1-point decrease in pain intensity and average pain intensity 4 were randomized to tapentadol PR (500mg/day) or tapentadol PR (300mg/day)/pregabalin (300mg/day) during an 8-week comparative period. ResultsIn 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 500mg/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). ConclusionsTapentadol PR 500mg is associated with comparable improvements in pain intensity and quality-of-life measures to tapentadol PR 300mg/pregabalin 300mg, 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.