title: Tapentadol prolonged release versus strong opioids for severe, chronic low back pain: results of an open-label, phase 3b study.
abstract: BACKGROUND
  This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50-250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to World Health Organization (WHO) step III opioids but tolerating treatment poorly. Equianalgesic ratios for tapentadol to prior strong opioids were calculated.
  
  
  METHODS
  Patients rotated directly from prior WHO step III opioids to tapentadol. Patients received tapentadol PR (50-250 mg b.i.d.) during 5-week titration and 7-week maintenance periods. Tapentadol immediate release (IR) 50 mg (≤ twice/day, ≥ 4 h apart) was allowed (total daily dose of tapentadol PR and IR ≤ 500 mg/day). The primary endpoint was responder rate 1 at week 6 (percentage of patients with the same or less pain intensity [11-point numerical rating scale (NRS; 3-day average)] vs week -1).
  
  
  RESULTS
  Responder rate 1 at week 6 (last observation carried forward [LOCF]) was 80.9% (76/94; P < 0.0001 vs. the null responder hypothesis rate [<60%]), resulting in a positive trial despite premature termination (136 recruited of 180 planned). Significant improvements from baseline in pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR (P < 0.05). Equianalgesic ratios were calculated for PR formulations alone and for PR and IR formulations combined for tapentadol to oxycodone, buprenorphine, fentanyl, morphine, and hydromorphone. The prevalences of adverse events reported as the reason for switching to tapentadol (most commonly constipation and nausea) decreased over time.
  
  
  CONCLUSIONS
  Tapentadol PR (50-250 mg b.i.d.) provided at least comparable pain relief and improved tolerability versus prior strong opioids in patients with severe, chronic low back pain responding to WHO step III therapy. Conversion from strong opioids to tapentadol PR, with its two mechanisms of action, went smoothly considering overall effectiveness and tolerability outcomes. Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies.
authors.affiliation: Unit of Pain and Palliative Care, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gálvez
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
authors.forename: Guy
authors.initials: G
authors.lastname: Hans
authors.forename: Dietmar
authors.initials: D
authors.lastname: Falke
authors.forename: Ilona
authors.initials: I
authors.lastname: Steigerwald
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002047:Buprenorphine / Q000627:therapeutic use; D059350:Chronic Pain / Q000188:drug therapy*; D003248:Constipation / Q000139:chemically induced / Q000517:prevention & control; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use; D006801:Humans; D004091:Hydromorphone / Q000627:therapeutic use; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy*; D010098:Oxycodone / Q000627:therapeutic use; D010147:Pain Measurement; D010636:Phenols / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010636:Phenols; D002047:Buprenorphine; D009020:Morphine; D010098:Oxycodone; D000077432:Tapentadol; D004091:Hydromorphone; D005283:Fentanyl