The European Journal of Health Economics

, Volume 14, Issue 6, pp 853–861 | Cite as

Cost-effectiveness analysis of top-down versus step-up strategies in patients with newly diagnosed active luminal Crohn’s disease

  • Monia Marchetti
  • Nicola L. Liberato
  • Antonio Di Sabatino
  • Gino R. Corazza
Original Paper

Abstract

Background

Top-down (TD) strategy with frontline infliximab proved to be more effective than the traditional step-up (SU) approach in newly diagnosed luminal moderate-to-severe CD patients. However, the considerable cost of infliximab calls its universal use as frontline treatment into question. The aim of this study is to evaluate the cost-effectiveness of the TD approach using a Markov decision model.

Methods

Four states were modelled, namely step 1, step 2, step 3 and death. The first three steps were in TD infliximab induction plus azathioprine, infliximab rechallenge plus azathioprine and steroids plus azathioprine, and in SU steroid induction, azathioprine plus steroid rechallenge and infliximab plus azathioprine. Each health state lasted 1 month. The time horizon of the model was 5 years. Transition probabilities and quality of life were estimated from a randomised trial. First- and second-order sensitivity analyses were done to test the robustness of the results.

Results

At baseline analysis, TD improved quality-adjusted life expectancy from 3.76 to 3.90 quality-adjusted life years (QALYs), that is, 0.14 QALYs, while allowing a saving of €773, proving dominant when compared to SU. TD was cost-saving in 66 % of the Monte Carlo simulations and cost <€20,000/QALY in 84 %. At sensitivity analysis the most significant variables were infliximab cost and time horizon: doubling infliximab cost (€1,000 per 100 mg vial) resulted in an incremental cost–utility ratio of €12,114/QALY.

Conclusions

TD is a cost-effective treatment in newly diagnosed CD patients with luminal moderate-to-severe disease, and sensitivity analysis showed the result to be robust.

Keywords

Cost-effectiveness Crohn’s disease Infliximab Step-up Top-down 

JEL Classification

I00 I19 

References

  1. 1.
    Targan, S.R., Hanauer, S.B., van Deventer, S.J., Mayer, L., Present, D.H., Braakman, T., DeWoody, K.L., Schaible, T.F., Rutgeerts, P.J.: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 study group. N. Engl. J. Med. 337, 1029–1035 (1997)PubMedCrossRefGoogle Scholar
  2. 2.
    Present, D.H., Rutgeerts, P., Targan, S., Hanauer, S.B., Mayer, L., van Hogezand, R.A., Podolsky, D.K., Sands, B.E., Braakman, T., DeWoody, K.L., Schaible, T.F., van Deventer, S.J.: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N. Engl. J. Med. 340, 1398–1405 (1999)PubMedCrossRefGoogle Scholar
  3. 3.
    Sandborn, W.J., Feagan, B.G., Hanauer, S.B., Present, D.H., Sutherland, L.R., Kamm, M.A., Wolf, D.C., Baker, J.P., Hawkey, C., Archambault, A., Bernstein, C.N., Novak, C., Heath, P.K., Targan, S.R.: CDP571 Crohn’s disease study group: an engineered human antibody to TNF (CDP571) for active Crohn’s disease: a randomized double-blind placebo-controlled trial. Gastroenterology 120, 1330–1338 (2001)PubMedCrossRefGoogle Scholar
  4. 4.
    Dignass, A., Van Assche, G., Lindsay, J.O., Lemann, M., Soderholm, J., Colombel, J.F., Danese, S., D’Hoore, A., Gassull, M., Gomollon, F., Hommes, D.W., Michetti, P., O’Morain, C., Oresland, T., Windsor, A., Stange, E.F., Travis, S.P.: European Crohn’s and Colitis Organisation (ECCO): the second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J. Crohn’s Colitis 4, 28–62 (2010)CrossRefGoogle Scholar
  5. 5.
    Lichtenstein, G.R., Abreu, M.T., Cohen, R., Tremaine, W.: American gastroenterological association: American gastroenterological association institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 130, 935–939 (2006)PubMedCrossRefGoogle Scholar
  6. 6.
    D’Haens, G.R., Panaccione, R., Higgins, P.D., Vermeire, S., Gassull, M., Chowers, Y., Hanauer, S.B., Herfarth, H., Hommes, D.W., Kamm, M., Lofberg, R., Quary, A., Sands, B., Sood, A., Watermeyer, G., Lashner, B., Lemann, M., Plevy, S., Reinisch, W., Schreiber, S., Siegel, C., Targan, S., Watanabe, M., Feagan, B., Sandborn, W.J., Colombel, J.F., Travis, S.: The London position statement of the world congress of gastroenterology on biological therapy for IBD with European Crohn’s and colitis organization: when to start, when to stop, which drug to choose, and how to predict response? Am. J. Gastroenterol. 106, 199–212 (2011)PubMedCrossRefGoogle Scholar
  7. 7.
    van Assche, G., Vermeire, S., Rutgeerts, P.: Mucosal healing and anti TNFs in IBD. Curr. Drug Targets 11, 227–233 (2010)PubMedCrossRefGoogle Scholar
  8. 8.
    van Assche, G., Vermeire, S., Rutgeerts, P.: The potential for disease modification in Crohn’s disease. Nat. Rev. Gastroenterol. Hepatol. 7, 79–85 (2010)PubMedCrossRefGoogle Scholar
  9. 9.
    Lémann, M., Mary, J.Y., Duclos, B., Veyrac, M., Dupas, J.L., Delchier, J.C., Laharie, D., Moreau, J., Cadiot, G., Picon, L., Bourreille, A., Sobahni, I., Colombel, J.F.: Group d’Etude therapeutique del affections inflammatoires du tube digestif (GETAID): infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial. Gastroenterology 130, 1054–1061 (2006)PubMedCrossRefGoogle Scholar
  10. 10.
    D’Haens, G., Baert, F., van Assche, G., Caenepeel, P., Vergauwe, P., Tuynman, H., De Vos, M., van Deventer, S., Stitt, L., Donner, A., Vermeire, S., Van de Mierop, F.J., Coche, J.C., van der Woude, J., Ochsenkuhn, T., van Bodegraven, A.A., Van Hootegem, P.P., Lambrecht, G.L., Mana, F., Rutgeerts, P., Feagan, B.G., Hommes, D.: Belgian inflammatory bowel diseae research group; North-Holland gut club: early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 371, 660–667 (2008)PubMedCrossRefGoogle Scholar
  11. 11.
    Baert, F.J., Moortgat, L., Van Assche, G.A., Caenepeel, P., Vergauwe, P.L., De Vos, M., Stokkers, P.C., Hommes, D.W., Vermeire, S., Ritgeerts, P.J., Feagan, B.G., D’Haens, G.: Mucosal healing predicts sustained clinical remission in early Crohn’s disease. Gastroenterology 134(suppl. 1), A640 (2008)Google Scholar
  12. 12.
    Silverstein, M.D., Loftus, E.V., Sandborn, W.J., Tremaine, W.J., Feagan, B.G., Nietert, P.J., Harmsen, W.S., Zinsmeister, A.R.: Clinical course and costs of care for Crohn’s disease: Markov model analysis of a population-based cohort. Gastroenterology 117, 49–57 (1999)PubMedCrossRefGoogle Scholar
  13. 13.
    Faraawi, R., Khraishi, M., Choquette, D., Bensen W., Nantel F.: The remitrac infusion registry: safety and management of infliximab infusions in a real-life setting. Gastroenterology 134 (Suppl 1), A-662 (2008)Google Scholar
  14. 14.
    Buxton, M.J., Lacey, L.A., Feagan, B.G., Niecko, T., Miller, D.W., Townend, R.J.: Mapping from disease-specific measures to utility: an analysis of the relationship between the inflammatory bowel disease questionnaire and Crohn’s disease activity index in Crohn’s disease and measures of utility. Value Health 10, 214–220 (2007)PubMedCrossRefGoogle Scholar
  15. 15.
    Casellas, F., Arenas, J., Badet, J.: Impairment of health-related quality of life in patients with inflammatory bowel disease: a Spanish multicenter study. Inflamm. Bowel Dis. 11, 488–496 (2005)PubMedCrossRefGoogle Scholar
  16. 16.
    Marchal, L., D’Haens, G., Van Assche, G., Vermeire, S., Noman, M., Ferrante, M., Hiele, M., Bueno De Mesquita, M., D’Hoore, A., Penninckx, F., Rutgeerts, P.: The risk of post-operative complications associated with infliximab therapy for Crohn’s disease: a controlled cohort study. Aliment. Pharmacol. Ther. 19, 749–754 (2004)PubMedCrossRefGoogle Scholar
  17. 17.
    Jewell, D.P., Satsangi, J., Lobo, A., Probert, C., Forbes, A., Ghosh, S., Shaffer, J., Frenz, M., Drummond, H., Troy, G., Turner, S., Younge, L., Evans, L., Moosa, M., Rodgers-Gray, B., Buchan, S.: Infliximab use in Crohn’s disease: impact on health care resources in the UK. Eur. J. Gastroenterol. Hepatol. 17, 1047–1052 (2005)PubMedCrossRefGoogle Scholar
  18. 18.
    National Institute for Health and Clinical Excellence (NICE). Guide to the methods of technology appraisal (June 2008). Available at: http://www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf. Accessed 8 Apr 2012
  19. 19.
    Hanauer, S.B., Feagan, B.G., Lichtenstein, G.R., Mayer, L.F., Schreiber, S., Colombel, J.F., Rachmilewitz, D., Wolf, D.C., Olson, A., Bao, W., Rutgeerts, P.: ACCENT I study group: maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 359, 1541–1549 (2002)PubMedCrossRefGoogle Scholar
  20. 20.
    Marshall, J., Blackhouse, G., Goeree, R., Brazier N., Irvine E., Faulkner L., Dipchand C., O’Brien B.: Infliximab for the treatment of Crohn’s disease: a systematic review and cost–utility analysis. Canadian Coordinating Office for Health Technology Assessment, Ottawa (2002). Technology report no 24. Available at: http://cadth.ca/media/pdf/122_infliximab_tr_e.pdf. Accessed 8 Apr 2012
  21. 21.
    Jaisson-Hot, I., Flouriè, B., Descos, L., Colin, C.: Management for severe Crohn’s disease: a lifetime cost–utility analysis. Int. J. Technol. Assess. Health Care 20, 274–279 (2004)PubMedCrossRefGoogle Scholar
  22. 22.
    Lindsay, J., Punekar, Y.S., Morris, J., Chung-Faye, G.: Health economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn’s disease—modelling outcomes in active luminal and fistulising disease in adults. Aliment. Pharmacol. Ther. 28, 76–87 (2008)PubMedCrossRefGoogle Scholar
  23. 23.
    Bodger, K., Kikuchi, T., Hughes, D.: Cost-effectiveness of biological therapy for Crohn’s disease: Markov cohort analyses incorporating United Kingdom patient-level cost data. Aliment. Pharmacol. Ther. 30, 265–274 (2009)PubMedCrossRefGoogle Scholar
  24. 24.
    Bernstein, C.N., Nabalamba, A.: Hospitalization, surgery, and readmission rates of IBD in Canada: a population-based study. Am. J. Gastroenterol. 101, 110–118 (2006)PubMedCrossRefGoogle Scholar
  25. 25.
    Yu, A.P., Cabanilla, L.A., Wu, E.Q., Mulani, P.M., Chao, J.: The costs of Crohn’s disease in the United States and other Western countries: a systematic review. Curr. Med. Res. Opin. 24, 319–328 (2008)PubMedCrossRefGoogle Scholar
  26. 26.
    Rubenstein, J.H., Chong, R.Y., Cohen, R.D.: Infliximab decreases resource use among patients with Crohn’s disease. J. Clin. Gastroenterol. 35, 151–156 (2002)PubMedCrossRefGoogle Scholar
  27. 27.
    Sprakes, M.B., Ford, A.C., Suares, N.C., Warren, L., Greer, D., Donnellan, C.F., Jennings, J.S., Everett, S.M., Hamlin, P.J.: Costs of care for Crohn’s disease following the introduction of infliximab: a single-centre UK experience. Aliment. Pharmacol. Ther. 32, 1357–1363 (2010)PubMedCrossRefGoogle Scholar
  28. 28.
    Saro, C., da la Coba, C., Casado, M.A., Morales, J.M., Otero, B.: Resource use in patients with Crohn’s disease treated with infliximab. Aliment. Pharmacol. Ther. 26, 1313–1323 (2007)PubMedCrossRefGoogle Scholar
  29. 29.
    Yu, A.P., Johnson, S., Wang, S.T., Atanasov, P., Tang, J., Wu, E., Chao, J., Mulani, P.M.: Cost-utility of adalimumab versus infliximab maintenance therapies in the United States for moderately to severely active Crohn’s disease. Pharmacoeconomics 27, 609–621 (2009)PubMedCrossRefGoogle Scholar
  30. 30.
    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. 7: 20 (2009). Available at: http://www.resource-allocation.com/content/pdf/1478-7547-7-20.pdf. Accessed 8 Apr 2012
  31. 31.
    Gregor, J.C., McDonald, J.W.D., Klar, N., Wall, R., Atkinson, K., Lamba, B., Feagan, B.G.: An evaluation of utility measures in Crohn’s disease. Inflamm. Bowel Dis. 3, 265–276 (1997)PubMedGoogle Scholar
  32. 32.
    Juan, J., Estiarte, R., Colomé, E., Artes, M., Jimenez, F.J., Alonso, J.: Burden of illness of Crohn’s disease in Spain. Dig. Liver Dis. 35, 853–861 (2003)PubMedCrossRefGoogle Scholar
  33. 33.
    Feagan, B.G., Bala, M., Yan, S., Olson, A., Hanauer, S.: Unemployment and disability in patients with moderately to severely active Crohn’s disease. J. Clin. Gastroenterol. 39, 390–395 (2005)PubMedCrossRefGoogle Scholar
  34. 34.
    Lichtenstein, G.R., Yan, S., Bala, M., Hanauer, S.: Remission in patients with Crohn’s disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries. Am. J. Gastroenterol. 99, 91–96 (2004)PubMedCrossRefGoogle Scholar
  35. 35.
    Colombel, J.F., Sandborn, W.J., Reinisch, W., Mantzaris, G.J., Kornbluth, A., Rachmilewitz, D., Lichtiger, S., D’Haens, G., Diamond, R.H., Broussard, D.L., Tang, K.L., van der Woude, C.J., Rutgeerts, P.: SONIC study group: infliximab, azathioprine, or combination therapy for Crohn’s disease. N. Engl. J. Med. 32, 1383–1395 (2010)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Monia Marchetti
    • 1
  • Nicola L. Liberato
    • 2
  • Antonio Di Sabatino
    • 3
  • Gino R. Corazza
    • 3
  1. 1.Department of Internal MedicineCardinal Massaia HospitalAstiItaly
  2. 2.Department of Internal MedicineAzienda Ospedaliera della Provincia di Pavia, Ospedale C. MiraCasorate PrimoItaly
  3. 3.First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche IntestinaliFondazione IRCCS Policlinico S. Matteo and University of PaviaPaviaItaly

Personalised recommendations