Skip to main content
SpringerLink
Log in

A Model-Based Economic Evaluation of Biologic and Non-Biologic Options for the Treatment of Adults with Moderately-to-Severely Active Ulcerative Colitis after the Failure of Conventional Therapy

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Background

Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. Medical management aims to induce and maintain remission and to avoid complications and the necessity for surgical intervention. Colectomy removes the source of inflammation but is associated with morbidity and mortality. Newer anti-tumour necrosis factor (TNF)-α therapies may improve medical outcomes, albeit at an increased cost.

Objective

Our objective was to assess the incremental cost effectiveness of infliximab, adalimumab and golimumab versus conventional therapy and surgery from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon.

Methods

A Markov model was developed with health states defined according to whether the patient is alive or dead, current treatments received, history of colectomy and level of disease control. Transition probabilities were derived from network meta-analyses (NMAs) of trials of anti-TNF-α agents in the moderate-to-severe UC population. Health utilities, colectomy rates, surgical complications and resource use estimates were derived from literature. Unit costs were drawn from standard costing sources and literature and were valued at year 2013/2014 values.

Results

For patients in whom surgery is an option, colectomy is expected to dominate all medical treatment options. For patients in whom colectomy is not an option, infliximab and golimumab are expected to be ruled out due to dominance, whilst the incremental cost-effectiveness ratio (ICER) for adalimumab versus conventional treatment is expected to be approximately £50,278 per quality-adjusted life-year (QALY) gained.

Conclusions

Based on the NMAs, the ICERs for anti-TNF-α therapy versus conventional treatment or surgery are expected to be at best, in excess of £50,000 per QALY gained. The cost effectiveness of withdrawing biologic therapy upon remission and re-treating relapse is unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. National Institute for Health and Care Excellence. Ulcerative colitis: Management in adults, children and young people. NICE Clinical Guideline Number 166. London: NICE; 2013, pp 1–37.

  2. Ford AC, Moayyedi P, Hanauer SB. Ulcerative colitis. Br Med J 2013; 346. http://www.bmj.com/content/346/bmj.f432.long. Accessed 01 May 2014.

  3. Bassi A, Dodd S, Williamson P, Bodger K. Cost of illness of inflammatory bowel disease in the UK: a single centre retrospective study. Gut. 2004;53(10):1471–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bayless TM, Hanauer SB. Advanced therapy in inflammatory bowel disease: volume 1—IBD and ulcerative colitis. 3rd ed. Shelton: Connecticut: People’s Medical Publishing House—USA; 2011.

  5. Royal College of Physicians. Report of the results for the national clinical audit of adult inflammatory bowel disease inpatient care in the UK. 1-67. London: RCP; 2012, p. 1–68.

  6. European Medicines Agency. Summary of product characteristics—infliximab. London: EMA; 2009. p. 1–56.

    Google Scholar 

  7. European Medicines Agency. Summary of product characteristics—adalimumab. London: EMA; 2009. p. 1–292.

    Google Scholar 

  8. European Medicines Agency. Summary of product characteristics—golimumab. London: EMA; 2009. p. 1–199.

    Google Scholar 

  9. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olsen A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462–76.

    Article  CAS  PubMed  Google Scholar 

  10. Reinisch W, Sandborn WJ, Hommes DW, D’Haens G, Hanauer SB, Schreiber S, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60(6):780–7.

    Article  CAS  PubMed  Google Scholar 

  11. Sandborn WJ, van Assche G, Reinisch W, Colombel JF, D’Haens G, Wolf DC, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257–65.

    Article  CAS  PubMed  Google Scholar 

  12. Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):85–95.

    Article  CAS  PubMed  Google Scholar 

  13. Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):96–109.

    Article  CAS  PubMed  Google Scholar 

  14. Suzuki Y, Motoya S, Hanai H, Matsumoto T, Hibi T, Robinson AM, et al. Efficacy and safety of adalimumab in Japanese patients with moderately to severely active ulcerative colitis. J Gastroenterol. 2014;49(2):283–94.

    Article  CAS  PubMed  Google Scholar 

  15. Panaccione R, Ghosh S, Middleton S, Márquez JR, Scott BB, Flint L, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146(2):392–400.

    Article  CAS  PubMed  Google Scholar 

  16. Probert CS, Hearing SD, Schreiber S, Kühbacher T, Ghosh S, Arnott ID, et al. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Gut. 2003;52(7):998–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. National Institute for Health and Care Excellence. Guide to the methods of technology appraisal. London: NICE; 2013. p. 1–102.

    Google Scholar 

  18. Archer R, Tappenden P, Ren S, Martyn St-James M, Harvey R, Basarir H et al. Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy: Clinical effectiveness systematic review and economic model. Final report to the National Institute for Health and Care Excellence. Sheffield: University of Sheffield 2014, p. 1–438.

  19. Cooney RM, Warren BF, Altman DG, Abreu MT, Travis SP. Outcome measurement in clinical trials for ulcerative colitis: towards standardisation. Trials 2007;8(17). http://www.trialsjournal.com/content/8/1/17. Accessed 01 June 2014).

  20. Woehl A, Hawthorne AB, McEwan P. The relation between disease activity, quality of life and health utility in patients with ulcerative colitis. Gut. 2008;57(Suppl1):A153.

    Google Scholar 

  21. Arseneau KO, Sultan S, Provenzale DT, Onken J, Bickston SJ, Foley E, et al. Do patient preferences influence decisions on treatment for patients with steroid-refractory ulcerative colitis? Clin Gastroenterol Hepatol. 2006;4(9):1135–42.

    Article  PubMed  Google Scholar 

  22. Solberg IC, Lygren I, Jahnsen J, Aadland E, Høie O, Cvancarova M, et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol. 2009;44(4):431–40.

    Article  PubMed  Google Scholar 

  23. Arai K, Koganei K, Kimura H, Akatani M, Kitoh F, Sugita A, et al. Incidence and outcome of complications following restorative proctocolectomy. Am J Surg. 2005;190(1):39–42.

    Article  PubMed  Google Scholar 

  24. BMJ Group and the Royal Pharmaceutical Society of Great Britain. Br Natl Formul. 2014. https://www.medicinescomplete.com/mc/bnf/current/. Accessed 01 May 2014.

  25. Tsai HH, Punekar YS, Morris J, Fortun P. A model of the long-term cost effectiveness of scheduled maintenance treatment with infliximab for moderate-to-severe ulcerative colitis. Aliment Pharmacol Therapeut. 2008;28(10):1230–9.

    Article  CAS  Google Scholar 

  26. Merck, Sharp, Dohme. Manufacturer’s submission of evidence to the National Institute for Health and Care Excellence: Infliximab. Hertfordshire: MSD; 2014.

  27. Department of Health. NHS Reference Costs 2012/13. London: DH. https://www.gov.uk/government/publications/nhs-reference-costs-2012-to-2013. Accessed 04 May 2014.

  28. Buchanan J, Wordsworth S, Ahmad T, Perrin A, Vermeire S, Sans M, et al. Managing the long term care of inflammatory bowel disease patients: The cost to European health care providers. J Crohn Colitis. 2011;5(4):301–16.

    Article  Google Scholar 

  29. Dias S, Welton N, Sutton A, Ades A. NICE Decision Support Unit Technical Support Document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. Sheffield: University of Sheffield; 2011. p. 1–98.

    Google Scholar 

  30. Thomas A, O’Hara B, Ligges U, Sturtz S. Making BUGS open. R News. 2015;6:12–7.

    Google Scholar 

  31. Office for National Statistics. Interim life tables 2009–2011. 2013. http://www.ons.gov.uk/ons/rel/lifetables/interim-life-tables/2009-2011/stb-2009-2011.html. Accessed 05 May 2014.

  32. Swinburn P, Elwick H, Bean K, Curry A, Patel S, Bodger K, et al. The impact of surgery on health related quality of life in ulcerative colitis. Gut. 2012;61(Suppl2):A237.

    Google Scholar 

  33. Van der Valk ME, Mangen MJ, Dijkstra G, Bodegraven AA, Fiddler H, De Jong DJ et al. Is there a difference in quality of life and costs between ulcerative colitis patients with a pouch or an ileostomy? Dig Dis Wk; 2012.

  34. Richards DM, Hughes SA, Irving MH, Scott NA. Patient quality of life after successful restorative proctocolectomy is normal. Colorectal Dis. 2001;3(4):223–6.

    Article  CAS  PubMed  Google Scholar 

  35. Kuruvilla K, Osler T, Hyman NH. A comparison of the quality of life of ulcerative colitis patients after IPAA vs ileostomy. Dis Colon Rectum. 2012;55(11):1131–7.

    Article  PubMed  Google Scholar 

  36. Curtis L. Unit costs of health and social care 2014. 1–294. Personal Social Services Research Unit: Kent; 2014.

  37. Xie F, Blackhouse G, Assasi N, Gaebel K, Robertson D, Goeree R. Cost-utility analysis of infliximab and adalimumab for refractory ulcerative colitis. Cost Eff Resour Alloc. 2009;7:20.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank MSD and AbbVie for providing additional data over the course of the National Institute for Health and Care Excellence (NICE) appraisal for which the model was developed.

Author Contributions

Paul Tappenden and Hasan Basarir developed the health economic model. Rachel Archer and Marrissa Martyn-St James undertook the systematic review of clinical effectiveness evidence. Shijie Ren, Rebecca Harvey and John Stevens undertook the network meta-analyses. Sami Hoque and Alan Lobo provided ongoing clinical advice during the model development. All authors contributed to the preparation of this manuscript. Paul Tappenden will act as the overall guarantor for this work.

Author information

Authors and Affiliations

  1. Health Economics and Decision Science, ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, Sheffield, England, UK

    Paul Tappenden, Shijie Ren, Rachel Archer, Rebecca Harvey, Marrissa Martyn-St James, Hasan Basarir & John Stevens

  2. Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, University of Sheffield, Sheffield, UK

    Alan Lobo

  3. Barts Health NHS Trust, London, UK

    Sami Hoque

Authors
  1. Paul Tappenden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shijie Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rachel Archer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rebecca Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marrissa Martyn-St James
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hasan Basarir
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John Stevens
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alan Lobo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sami Hoque
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Tappenden.

Ethics declarations

Conflict of interest

This study was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme to inform the NICE Technology Appraisal Programme (Project Number 12/51/01). Alan Lobo has received money for attending an advisory board for Takeda Pharmaceuticals. Paul Tappenden, Shijie Ren, Rachel Archer, Rebecca Harvey, Marrissa Martyn-St James, Hasan Basarir, John Stevens and Sami Hoque do not have any conflicts of interest to declare.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 22 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tappenden, P., Ren, S., Archer, R. et al. A Model-Based Economic Evaluation of Biologic and Non-Biologic Options for the Treatment of Adults with Moderately-to-Severely Active Ulcerative Colitis after the Failure of Conventional Therapy. PharmacoEconomics 34, 1023–1038 (2016). https://doi.org/10.1007/s40273-016-0409-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40273-016-0409-9

Keywords

Search

Navigation