title: Impact of Treatment with Naloxegol for Opioid-Induced Constipation on Patients' Health State Utility.
abstract: Opioid-induced constipation (OIC) is the most common side effect of opioid treatment. Treatment for OIC typically involves a laxative. However, some patients have an inadequate response to these (laxative inadequate responders, or LIR). This has led to the development of treatments such as naloxegol. This analysis estimates the impact of naloxegol on the health state utility of LIR patients, examines if this utility impact is driven by the change in OIC status, and estimates the utility impact of relief of OIC.
  
  
  
  The analysis was conducted using data from two 12-week randomized controlled trials, KODIAC 4 (ClinicalTrials.gov identifier, NCT01309841) and KODIAC 5 (ClinicalTrials.gov identifier, NCT01323790), plus KODIAC 7 (ClinicalTrials.gov identifier, NCT01395524), a 12-week extension to KODIAC 4. All were designed to assess the efficacy and safety of oral naloxegol (12.5 and 25 mg) compared to placebo. Health state utility data were collected through the EuroQol-five dimensions questionnaire (EQ-5D-3L). Descriptive analysis was undertaken to estimate how EQ-5D utility scores and EQ-5D domain responses varied with treatment, OIC status, and over time. A repeated measure mixed-effects model was used to predict the change from baseline in health state utility score over time.
  
  
  
  Compared with placebo, LIR patients treated with naloxegol 25 mg reported a 0.08 improvement in the EQ-5D overall score after 12 weeks of treatment. The analyses also suggest that change in OIC status is a key driver of the impact of OIC treatment on health state utility. When other factors are controlled, relieving OIC is associated with a 0.05 improvement in health state utility, although treatment with naloxegol is associated with an improvement in health state utility over and above the improvement in OIC status.
  
  
  
  These analyses suggest that treatment with naloxegol improves patients' health state utility; driven predominantly by the relief of patients' constipation.
  
  
  
  AstraZeneca.
authors.affiliation: AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA. Richard.Lawson1@astrazeneca.com.
authors.forename: Richard
authors.initials: R
authors.lastname: Lawson
authors.affiliation: AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: King
authors.affiliation: Evidera, Metro Building, 6th Floor, 1 Butterwick, London, W6 8DL, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: Evidera, 430 Bedford Street, Suite 300, Lexington, MA, 02420, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Altincatal
authors.affiliation: AstraZeneca, Melbourn Science Park, Melbourn, Herts, SG8 6EE, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Cimen
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011788:Quality of Life
chemical_list: D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D011092:Polyethylene Glycols; C000589308:naloxegol
keywords: Constipation; EQ-5D; Gastroenterology; Health related quality of life; Laxative inadequate responder (LIR); Naloxegol; OIC; Opioid-induced constipation; Pain; Utility