title: 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.
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.
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital, Schleswig-Holstein Campus Kiel, Kiel, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.affiliation: Department of Rheumatology, University Hospital La Paz, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Martin-Mola
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Global Biometrics in Grünenthal Innovation, Grünenthal GmbH, Aachen, Germany.
authors.forename: Cecile
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Falke
authors.affiliation: Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Steigerwald
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage; D059350:Chronic Pain / Q000175:diagnosis / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D038622:Internationality; D017116:Low Back Pain / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000175:diagnosis / Q000188:drug therapy*; D059408:Pain Management / Q000379:methods*; D010636:Phenols / Q000008:administration & dosage*; D000069583:Pregabalin / Q000008:administration & dosage*; D012720:Severity of Illness Index; D000077432:Tapentadol; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D010636:Phenols; D000069583:Pregabalin; D000077432:Tapentadol
keywords: chronic pain; combination therapy; low back pain; neuropathic pain; randomized controlled trial; tapentadol prolonged release