title: Treatment with prolonged-release oxycodone/naloxone improves pain relief and opioid-induced constipation compared with prolonged-release oxycodone in patients with chronic severe pain and laxative-refractory constipation.
abstract: OBJECTIVE
  Laxative-refractory opioid-induced constipation (OIC) is defined as OIC despite using 2 laxatives with a different mechanism of action (based on the Anatomical Therapeutic Chemical Classification System level 4 term [contact laxatives, osmotically acting laxatives, softeners/emollients, enemas, and others]). OIC has a significant impact on the treatment and quality of life of patients with severe chronic pain. This noninterventional, observational, real-life study in Belgium investigated the efficacy of prolonged-release oxycodone/naloxone combination (PR OXN) treatment regarding pain relief and OIC compared with previous prolonged-release oxycodone (PR OXY) treatment for laxative-refractory OIC in daily clinical practice.
  
  
  METHODS
  Laxative-refractory OIC patients with severe chronic pain were treated with PR OXN for 12 weeks (3 visits). Pain relief (assessed on a numerical rating scale) and OIC (assessed by using the Bowel Function Index [BFI]) were evaluated at each visit. A responder was defined as a patient who had: (1) no worsening of pain at the last visit compared with visit 1 or a numerical rating scale ≤4 at visit 3/last visit; and (2) a reduction in BFI ≥12 units at visit 3/last visit compared with visit 1; or (3) a BFI ≤28.8 at visit 3/last visit.
  
  
  RESULTS
  Sixty-eight laxative-refractory OIC patients with severe chronic pain (mean (sd) age 59.8 (13.3) years, 67.6% female and 91.2% non-malignant pain) were treated for 91 days with PR OXN (median daily dose, 20 mg). Treatment with PR OXN resulted in a significant and clinically relevant decrease of pain of 2.1 units (P < 0.001; 95% CI, 1.66-2.54) and of BFI by 48.5 units (P < 0.001; 95% CI, 44.4-52.7) compared with PR OXY treatment; use of laxatives was also significantly reduced (P < 0.001). Approximately 95% of patients were responders, and quality of life (as measured by using the EQ-5D) improved significantly. Adverse events were opioid related, and PR OXN treatment was well tolerated.
  
  
  CONCLUSIONS
  Treatment with PR OXN resulted in a significant and clinically relevant reduction in OIC compared with previous PR OXY treatment for these patients with severe chronic pain and laxative-refractory OIC. Treatment with PR OXN also resulted in a significant improvement in pain relief and quality of life. ClinicalTrials.gov identifier: NCT01710917.
authors.affiliation: University Hospital Brussel (VUB), Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Poelaert
authors.affiliation: Mundipharma Pharmaceuticals BV, the Netherlands.
authors.forename: Gineke
authors.initials: G
authors.lastname: Koopmans-Klein
authors.affiliation: Les Cliniques ISOSL, sites Valdor-Péri, Lièges, Belgium.
authors.forename: Alioune
authors.initials: A
authors.lastname: Dioh
authors.affiliation: Clinique Sainte-Elisabeth, Heusy.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Louis
authors.affiliation: AZ Sint-Jan, Brugge, Belgium.
authors.forename: Mayken
authors.initials: M
authors.lastname: Gorissen
authors.affiliation: AZ Sint-Lucas, Gent.
authors.forename: David
authors.initials: D
authors.lastname: Logé
authors.affiliation: Mundipharma Comm. VA, Belgium.
authors.forename: Joeri
authors.initials: J
authors.lastname: Van Op den Bosch
authors.affiliation: Mundipharma Pharmaceuticals BV, the Netherlands. Electronic address: yvonne.vanmegen@mundipharma.nl.
authors.forename: Yvonne J B
authors.initials: YJ
authors.lastname: van Megen
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D003248:Constipation / Q000139:chemically induced / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D006801:Humans; D054368:Laxatives / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000009:adverse effects / Q000627:therapeutic use*; D010098:Oxycodone / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D054368:Laxatives; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone
keywords: laxative refractory; laxatives; opioid-induced constipation; pain; quality of life