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Cost Effectiveness of Naloxegol for Opioid-Induced Constipation in the UK

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Abstract

Background and Objectives

Opioid-induced constipation (OIC) is the most common adverse effect reported in patients receiving opioids to manage pain. Initial treatment with laxatives provides inadequate response in some patients. Naloxegol is a peripherally acting µ-opioid receptor antagonist used to treat patients with inadequate response to laxative(s) (laxative inadequate responder [LIR]). A cost-effectiveness model was constructed from the UK payer perspective to compare oral naloxegol 25 mg with placebo in non-cancer LIR patients receiving opioids for chronic pain, and a scenario analysis of naloxegol 25 mg with rescue laxatives compared with placebo with rescue laxatives in the same patient population.

Methods

The model comprised a decision tree for the first 4 weeks of treatment, followed by a Markov model with a 4-week cycle length and the following states: ‘OIC’, ‘non-OIC (on treatment)’, ‘non-OIC (untreated)’ and ‘death’. Two phase III trials with a follow-up period of 12 weeks provided data on treatment efficacy, transition probabilities, adverse event frequency and patient utility. Resource utilisation data were sourced from a UK-based burden of illness study and physician surveys. A UK National Health Service and Personal Social Service perspective was adopted; costs and health-related quality of life gains were discounted at a rate of 3.5 %. The model was run over a time horizon of 5 years, reflecting the average period of opioid use.

Results

Naloxegol has an incremental cost-effectiveness ratio of £10,849 per quality-adjusted life-year gained versus placebo, and £11,179 when rescue laxatives are made available in both arms (2014 values). Model outcomes were only sensitive to variations in utility inputs. However, the probabilistic sensitivity analyses indicate that naloxegol has a 91 % probability of being cost effective at a £20,000 threshold when compared with placebo.

Conclusions

Naloxegol is likely a cost-effective treatment option for LIR patients with OIC. This assessment should be supported by further work on the utility of patients with OIC, including how utility varies with more granular measures of OIC.

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Notes

  1. The Advisory Board consisted of a panel of 11 clinicians and health economists from UK, France, Canada, Germany, Italy, The Netherlands and Sweden who gathered together in July 2013. The meeting was structured as a series of presentations, with a question-and-answer session after each presentation. Specific topics discussed during the meeting included model structure, the natural history of OIC, long-term response rates, discontinuation, adverse events, cost inputs and resource use, and utility. The proposed modelling approach was presented to the Advisory Board and the chair facilitated a discussion of the approach; based on the discussion, the chair proposed an approach for the Advisory Board to consider. Any concerns were resolved through further debate. Where consensus was not possible, scenario analysis was proposed to explore this uncertainty.

References

  1. Kumar L, Barker C, Emmanuel A. Opioid-induced constipation: pathophysiology, clinical consequences, and management. Gastroenterol Res Pract. 2014;2014:141737.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014;6:269–81.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 2009;10(1):35–42.

    Article  PubMed  Google Scholar 

  4. Guijarro P, Alonso-Babarro A, Viqueira A, Fernandez G. Economic burden of opioid induced constipation in Spain. Value Health. 2010;13(7):A369.

    Article  Google Scholar 

  5. Müller-Lissner S. Opioid-induced constipation–mechanisms, relevance and management. Eur Gastroenterol Hepatol Rev. 2010;6(1):54–7.

    Google Scholar 

  6. Webster L, Chey WD, Tack J, Lappalainen J, Diva U, Sostek M. Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation. Aliment Pharmacol Ther. 2014;40(7):771–9.

    Article  CAS  PubMed  Google Scholar 

  7. Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014;370(25):2387–96.

    Article  PubMed  Google Scholar 

  8. AstraZeneca. MOVENTIG® approved in the European Union for opioid-induced constipation. 9 Dec 2014. https://www.astrazeneca.com/media-centre/press-releases/2014/moventig-approved-european-union-opioid-induced-constipation-09122014.html. Accessed 1 Aug 2016.

  9. National Institute for Health and Care Excellence (NICE). Guide to the methods of technology appraisal. NICE process and methods guide no. 9. 2013. https://www.nice.org.uk/process/pmg9/chapter/foreword. Accessed 5 June 2015.

  10. Dunlop W, Uhl R, Khan I, Taylor A, Barton G. Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: a UK cost-utility analysis. J Med Econ. 2012;15(3):564–75.

    Article  PubMed  Google Scholar 

  11. Napp Pharmaceuticals Ltd. Oxycodone/naloxone 10mg/5mg and 20mg/10mg prolongedreleasetablets (Targinact®), no. 541/09. Scottish Medicines Consortium. Scotland: NHS; 2009. https://www.scottishmedicines.org.uk/files/oxycodonenaloxone_Targinact_.pdf.

  12. Earnshaw SR, Klok RM, Iyer S, McDade C. Methylnaltrexone bromide for the treatment of opioid-induced constipation in patients with advanced illness—a cost-effectiveness analysis. Aliment Pharmacol Ther. 2010;31(8):911–21.

    CAS  PubMed  Google Scholar 

  13. Pharmaceutical Benefits Advisory Committee (PBAC). Public Summary Document: oxycodone hydrochloride and naloxone hydrochloride dihydrate, tablets, 5 mg–2.5 mg, 10 mg–5 mg, 20 mg–10 mg and 40 mg–20 mg (controlled release). Targin®, 2010. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2010-07/pbac-psd-Oxycodone-july10. Accessed 9 Sept 2016.

  14. Scottish Medicines Consortium (SMC). Oxycodone/naloxone 10 mg/5 mg and 20 mg/10 mg prolonged release tablets (Targinact®). No. 541/09. 2009. http://www.scottishmedicines.org.uk/files/oxycodonenaloxone_Targinact_.pdf. Accessed 20 May 2015.

  15. National Institute for Health and Care Excellence (NICE). Premeeting briefing: naloxegol for treating opioid-induced constipation. 2015. https://www.nice.org.uk/guidance/TA345/documents/constipation-opioidinduced-naloxegol-committee-papers2. Accessed 1 Aug 2016.

  16. AstraZeneca. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of NKTR-118 in patients with non-cancer-related pain and opioid-induced constipation (OIC). KODIAC 4 clinical study report. AstraZeneca; 2013. (Data on file).

  17. AstraZeneca. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of NKTR-118 in patients with non-cancer-related pain and opioid-induced constipation (OIC). KODIAC 5 clinical study report. AstraZeneca; 2013. (Data on file).

  18. Office for National Statistics. United Kingdom, interim life tables, 1980–1982 to 2008–2010 2011. http://www.ons.gov.uk/ons/datasets-and-tables/index.html?pageSize=50&sortBy=none&sortDirection=none&newquery=interim+life+table+united+kingdom. Accessed 20 May 2015.

  19. National Health Service England and Wales. NHS Electronic Drug Tariff. 2016. http://www.drugtariff.nhsbsa.nhs.uk/#/00336026-DD_1/DD00336022/Home. Accessed 1 Aug 2016.

  20. British National Formulary (BNF) [available by subscription]. 2014. https://www.bnf.org/. Accessed 29 Sept 2014.

  21. MedeConnect Healthcare Insight. GP omnibus chronic pain and OIC research. AZN055205938. 2014.

  22. National schedule of reference costs year: 2012–13. NHS trusts and PCTs combined. Inflated to 2014. https://www.gov.uk/government/publications/nhs-reference-costs-2012-to-2013. Accessed 1 Sept 2014.

  23. Unit costs of health & social care 2011. PSSRU. Inflated to 2014. http://www.pssru.ac.uk/project-pages/unit-costs/. Accessed 1 Sept 2014.

  24. Unit costs of health & social care 2012. PSSRU. Inflated to 2014. http://www.pssru.ac.uk/project-pages/unit-costs/. Accessed 1 Sept 2014.

  25. Unit costs of health & social care 2013. PSSRU. Inflated to 2014. http://www.pssru.ac.uk/project-pages/unit-costs/. Accessed 1 Sept 2014.

  26. Lawson R, Marsh K, Altincatal A, King F. How does non-malignant opioid-induced constipation impact health state utility? [Poster no. PGI36]. ISPOR 17th Annual European Congress, 8–12 Nov 2014, Amsterdam.

  27. Hatswell AJ, Vegter S. Measuring quality of life in opioid-induced constipation: mapping EQ-5D-3 L and PAC-QOL. Health Econ Rev. 2016;6(1):14.

    Article  PubMed  PubMed Central  Google Scholar 

  28. European Medicines Agency. Relistor. Summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000870/WC500050562.pdf. Accessed 1 Sept 2014.

  29. eMC. Targinact 5 mg/2.5 mg, 10 mg/5 mg, 20 mg/10 mg and 40 mg/20 mg prolonged-release tablets SPC. 2015. http://www.medicines.org.uk/emc/medicine/22908. Accessed 1 Sept 2014.

  30. Latimer N. NICE DSU technical support document 14: survival analysis for economic evaluations alongside clinical trials-extrapolation with patient-level data. Report by the Decision Support Unit (DSU). 2011. http://www.nicedsu.org.uk/NICE%20DSU%20TSD%20Survival%20analysis.updated%20March%202013.v2.pdf. Accessed 8 June 2015.

  31. Rome Foundation Inc. Rome III diagnostic criteria for functional gastrointestinal disorders. Appendix A. Rome III: the functional gastrointestinal disorders. Third edition 2006. http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Accessed 8 June 2015.

  32. Hasal K. Five categories of lower gastrointestinal functional bowel disorders in revised Rome IV criteria. Digestive Disease Week, 21–24 May 2016, San Diego.

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Author contributions

All authors contributed equally to the development of the economic model and the writing and review of this article.

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Authors and Affiliations

  1. AstraZeneca Global Payer and Pricing (GPEP), 101 Orchard Ridge Drive, Gaithersburg, MD, 20878, USA

    Richard Lawson & Frederic King

  2. AstraZeneca Global Payer and Pricing (GPEP), Da Vinci Building, Melbourn Science Park, Hertfordshire, SG8 6EE, UK

    James Ryan

  3. Evidera Inc., 7101 Wisconsin Ave, Suite 1400, Bethesda, MD, 20814, USA

    Jo Wern Goh

  4. Evidera Inc., Metro Building 6th Floor, 1 Butterwick, London, W6 8DL, UK

    Eszter Tichy & Kevin Marsh

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Correspondence to Kevin Marsh.

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Funding

AstraZeneca provided the funding for the study described in this article and for the production of the article itself. AstraZeneca is the manufacturer of naloxegol.

Conflict of interest

Richard Lawson, James Ryan and Frederic King are all employees and shareholders of AstraZeneca, which manufactures naloxegol and provided funding for the project described in this article and the article itself. Kevin Marsh, Jo Wern Goh and Eszter Tichy are all employees of Evidera, which provides consulting and other research services to pharmaceutical, medical device and other organisations. In their salaried positions, they work with a variety of companies and are precluded from receiving payment or honoraria directly from these organisations for services rendered. Evidera received funding from AstraZeneca to undertake the analysis and support the manuscript development.

Overall guarantor

Kevin Marsh serves as overall guarantor for this study and article.

Ethical approval

For this type of study, formal consent is not required, so we did not submit our study to an independent ethics committee or institutional review board. This article does not contain any studies with human participants or animals performed by any of the authors.

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Lawson, R., Ryan, J., King, F. et al. Cost Effectiveness of Naloxegol for Opioid-Induced Constipation in the UK. PharmacoEconomics 35, 225–235 (2017). https://doi.org/10.1007/s40273-016-0454-4

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