title: Efficacy of subcutaneous methylnaltrexone in the treatment of opioid-induced constipation: a responder post hoc analysis.
abstract: OBJECTIVE
  Methylnaltrexone, a selective peripherally acting mu-opioid receptor antagonist, effectively treats opioid-induced constipation (OIC) in patients with advanced illness and shows efficacy in patients with chronic nonmalignant pain. The objective was to identify patients who achieved maximal treatment effect based on response to initial four methylnaltrexone doses.
  
  
  METHODS
  A post hoc analysis of a randomized, double-blind, placebo-controlled study evaluating patients with OIC and chronic nonmalignant pain who received 12 mg subcutaneous methylnaltrexone daily for 4 weeks was performed to determine if response to the first four methylnaltrexone doses predicted overall response during the study. Patients receiving ≥8 doses were included.
  
  
  METHODS
  Patients having ≥3 rescue-free bowel movements (RFBMs)/week; change from baseline in RFBMs/week; percentage of doses with RFBMs within 4 hours after dosing.
  
  
  RESULTS
  Of 137 patients, 58 patients (42.3%) had RFBMs after ≥2 of four doses. Among those with response to ≥2 of four doses, 81% had ≥3 RFBMs/week vs. 43% for those with response to <2 of four (P < 0.0001). Those with RFBMs after ≥2 of first four doses averaged 4.8 RFBMs/week vs. 2.0 RFBMs/week for those with <2 of four (P < 0.0001). Percentage of subsequent injections resulting in RFBMs within 4 hours was 45.9 ± 27.6 for those with response to ≥2 of four doses vs. 17.1 ± 19.1 for those with response to <2 of four (P < 0.0001). Abdominal pain was the most frequently reported adverse event.
  
  
  CONCLUSIONS
  Early response to ≥2 of first four doses of methylnaltrexone identified patients who demonstrated a particularly robust effect of treatment over the duration of use.
authors.affiliation: Pain Management Center, Brigham and Women's Hospital, Boston, Massachusetts 02467, USA. emichna@partners.org
authors.forename: Edward
authors.initials: E
authors.lastname: Michna
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Weil
authors.forename: Marc
authors.initials: M
authors.lastname: Duerden
authors.forename: Seth
authors.initials: S
authors.lastname: Schulman
authors.forename: Wenjin
authors.initials: W
authors.lastname: Wang
authors.forename: Evan
authors.initials: E
authors.lastname: Tzanis
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Dahong
authors.initials: D
authors.lastname: Yu
authors.forename: Amy
authors.initials: A
authors.lastname: Manley
authors.forename: Bruce
authors.initials: B
authors.lastname: Randazzo
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010919:Placebos; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone