Optimal use and cost-effectiveness of biologic therapies in inflammatory bowel disease

  • Antonio Di Sabatino
  • Lucio Liberato
  • Monia Marchetti
  • Paolo Biancheri
  • Gino R. Corazza


Inflammatory bowel diseases (IBD), namely Crohn’s disease and ulcerative colitis, are burdened by high medical costs which are mostly dependent on hospital inpatient treatment. New biologic therapies, which target specific cytokines in the inflammatory cascade leading to the intestinal lesions, including tumor necrosis factor (TNF)-α, have revolutionized the management of IBD by offering a therapeutic chance to patients in whom conventional therapies failed. However, the relatively high costs of biologic drugs, together with their potential toxicity due to infections and malignancies, have led to debate regarding their indiscriminate use in IBD patients. The purpose of this review is to deal with the optimal use and cost-effectiveness of the two main monoclonal anti-TNF-α agents currently used in the management of IBD patients, i.e. the chimeric human/murine antibody infliximab and the fully human antibody adalimumab.


Adalimumab Hospitalization Infliximab Mucosal healing Surgery Top-down 



Anti-drug antibodies


Crohn’s disease


C-reactive protein


Inflammatory bowel disease


Quality-adjusted life years


Tumor necrosis factor


Ulcerative colitis


  1. 1.
    MacDonald TT, Monteleone G (2005) Immunity, inflammation, and allergy in the gut. Science 307:1920–1925PubMedCrossRefGoogle Scholar
  2. 2.
    Macdonald TT, Monteleone I, Fantini MC, Monteleone G (2011) Regulation of homeostasis and inflammation in the intestine. Gastroenterology 140:1768–1775PubMedCrossRefGoogle Scholar
  3. 3.
    Cosnes J, Gower-Rousseau C, Seksik P, Cortot A (2011) Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 140:1785–1794PubMedCrossRefGoogle Scholar
  4. 4.
    Baumgart DC, Sandborn WJ (2007) Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 369:1641–1657PubMedCrossRefGoogle Scholar
  5. 5.
    Di Sabatino A, Rovedatti L, Vidali F et al (2011) Recent advances in understanding Crohn’s disease. Intern Emerg Med (Epub ahead of print)Google Scholar
  6. 6.
    Kappelman MD, Rifas-Shiman SL, Porter C et al (2008) Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology 135:1907–1913PubMedCrossRefGoogle Scholar
  7. 7.
    Bodger K (2011) Cost effectiveness of treatments for inflammatory bowel disease. Pharmacoeconomics 29:387–401PubMedCrossRefGoogle Scholar
  8. 8.
    Yu AP, Cabanilla LA, Wu EQ et al (2008) The costs of Crohn’s disease in the United States and other Western countries: a systematic review. Curr Med Res Opin 24:319–328PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen RD, Yu AP, Wu EQ et al (2010) Systematic review: the costs of ulcerative colitis in Western countries. Aliment Pharmacol Ther 31:693–707PubMedCrossRefGoogle Scholar
  10. 10.
    MacDonald TT, Di Sabatino A, Gordon JN (2005) Immunopathogenesis of Crohn’s disease. JPEN J Parenter Enter Nutr 29:S118–S124CrossRefGoogle Scholar
  11. 11.
    Di Sabatino A, Biancheri P, Rovedatti L et al (2011) New pathogenic paradigms in inflammatory bowel disease. Inflamm Bowel Dis (Epub ahead of print)Google Scholar
  12. 12.
    Gordon JN, Di Sabatino A, MacDonald TT (2005) The pathophysiologic rationale for biological therapies in inflammatory bowel disease. Curr Opin Gastroenterol 21:431–437PubMedGoogle Scholar
  13. 13.
    MacDonald TT, Hutchings P, Choy MY et al (1990) Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 81:301–305PubMedCrossRefGoogle Scholar
  14. 14.
    Neurath MF, Fuss I, Pasparakis M et al (1997) Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. Eur J Immunol 27:1743–1750PubMedCrossRefGoogle Scholar
  15. 15.
    Targan SR, Hanauer SB, van Deventer SJ et al (1997) 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 337:1029–1035PubMedCrossRefGoogle Scholar
  16. 16.
    Chowers Y, Allez M (2010) Efficacy of anti-TNF in Crohn’s disease: how does it work? Curr Drug Targets 11:138–142PubMedCrossRefGoogle Scholar
  17. 17.
    Di Sabatino A, Ciccocioppo R, Cinque B et al (2004) Defective mucosal T cell death is sustainably reverted by infliximab in a caspase-dependent pathway in Crohn’s disease. Gut 53:70–77PubMedCrossRefGoogle Scholar
  18. 18.
    Nesbitt A, Fossati G, Bergin M et al (2007) Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm Bowel Dis 13:1323–1332PubMedCrossRefGoogle Scholar
  19. 19.
    Di Sabatino A, Pender SLF, Jackson CL et al (2007) Functional modulation of Crohn’s disease myofibroblasts by anti-TNF antibodies. Gastroenterology 133:137–149PubMedCrossRefGoogle Scholar
  20. 20.
    Di Sabatino A, Saarialho-Kere U, Buckley MG et al (2009) Stromelysin-1 and macrophage metalloelastase expression in the intestinal mucosa of Crohn’s disease patients treated with infliximab. Eur J Gastroenterol Hepatol 21:1049–1055PubMedCrossRefGoogle Scholar
  21. 21.
    Danese S, Sans M, Scaldaferri F et al (2006) TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn’s disease. J Immunol 176:2617–2624PubMedGoogle Scholar
  22. 22.
    Sandborn WJ, Hanauer SB, Katz S et al (2001) Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 121:1088–1094PubMedCrossRefGoogle Scholar
  23. 23.
    Bourne T, Fossati G, Nesbitt A (2008) A PEGylated Fab’ fragment against tumor necrosis factor for the treatment of Crohn disease: exploring a new mechanism of action. BioDrugs 22:331–337PubMedCrossRefGoogle Scholar
  24. 24.
    Peyrin-Biroulet L (2010) Anti-TNF therapy in inflammatory bowel diseases: a huge review. Minerva Gastroenterol Dietol 56:233–243PubMedGoogle Scholar
  25. 25.
    Ford AC, Sandborn WJ, Khan KJ et al (2011) Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 106:644–659PubMedCrossRefGoogle Scholar
  26. 26.
    Bergamaschi G, Di Sabatino A, Albertini R et al (2010) Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-alpha treatment. Haematologica 95:199–205PubMedCrossRefGoogle Scholar
  27. 27.
    Rispo A, Scarpa R, Di Girolamo E et al (2005) Infliximab in the treatment of extra-intestinal manifestations of Crohn’s disease. Scand J Rheumatol 34:387–391PubMedCrossRefGoogle Scholar
  28. 28.
    Brooklyn TN, Dunnill MG, Shetty A et al (2006) Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 55:505–509PubMedCrossRefGoogle Scholar
  29. 29.
    Modigliani R, Mary JY, Simon JF et al (1990) Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Evolution on prednisolone. Gastroenterology 98:811–818PubMedCrossRefGoogle Scholar
  30. 30.
    Hanauer SB, Feagan BG, Lichtenstein GR et al (2002) Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 359:1541–1549PubMedCrossRefGoogle Scholar
  31. 31.
    Rutgeerts P, D’Haens GR, Van Assche GA et al (2009) Adalimumab induces and maintains mucosal healing in patients with moderate to severe ileocolonic Crohn’s disease—first results of the Extend Trial. Gastroenterology 136:A116CrossRefGoogle Scholar
  32. 32.
    Schnitzler F, Fidder H, Ferrante M et al (2009) Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis 15:1295–1301PubMedCrossRefGoogle Scholar
  33. 33.
    Peyrin-Biroulet L, Deltenre P, de Suray N et al (2008) Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 6:644–653PubMedCrossRefGoogle Scholar
  34. 34.
    Ardizzone S, Cassinotti A, Duca P et al (2010) Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol (Epub ahead of print)Google Scholar
  35. 35.
    Carbonnel F, Gargouri D, Lémann M et al (2000) Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis. Aliment Pharmacol Ther 14:273–279PubMedCrossRefGoogle Scholar
  36. 36.
    Järnerot G, Hertervig E, Friis-Liby I et al (2005) Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 128:1805–1811PubMedCrossRefGoogle Scholar
  37. 37.
    Ferrante M, Vermeire S, Katsanos KH et al (2007) Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm Bowel Dis 13:123–128PubMedCrossRefGoogle Scholar
  38. 38.
    Rutgeerts P, Sandborn WJ, Feagan BG et al (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353:2462–2476PubMedCrossRefGoogle Scholar
  39. 39.
    Dignass A, Van Assche G, Lindsay JO et al (2010) The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 4:28–62PubMedCrossRefGoogle Scholar
  40. 40.
    Orlando A, Armuzzi A, Papi C et al (2011) The Italian Society of Gastroenterology and the Italian Group for the study of Inflammatory Bowel Disease. Clinical Practice Guidelines: the use of tumor necrosis factor-alpha antagonist therapy in inflammatory bowel disease. Dig Liver Dis 43:1–20PubMedCrossRefGoogle Scholar
  41. 41.
    D’Haens GR, Panaccione R, Higgins PD et al (2011) The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol 106:199–212PubMedCrossRefGoogle Scholar
  42. 42.
    Travis SP, Stange EF, Lémann M et al (2008) European evidence-based Consensus on the management of ulcerative colitis: current management. J Crohns Colitis 2:24–62PubMedCrossRefGoogle Scholar
  43. 43.
    D’Haens GR (2010) Top-down therapy for IBD: rationale and requisite evidence. Nat Rev Gastroenterol Hepatol 7:86–92PubMedCrossRefGoogle Scholar
  44. 44.
    D’Haens G, Baert F, van Assche G et al (2008) Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 371:660–667PubMedCrossRefGoogle Scholar
  45. 45.
    Schreiber S, Reinisch W, Colombel JF et al (2007) Early Crohn’s disease shows high levels of remission to therapy with adalimumab: subanalysis of CHARM. Gastroenterology 132:A147Google Scholar
  46. 46.
    Kugathasan S, Saubermann LJ, Smith L et al (2007) Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease. Gut 56:1696–7105PubMedCrossRefGoogle Scholar
  47. 47.
    Beaugerie L, Seksik P, Nion-Larmurier I et al (2006) Predictors of Crohn’s disease. Gastroenterology 130:650–656PubMedCrossRefGoogle Scholar
  48. 48.
    Lewis JD (2011) The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology 140:1817–1826PubMedCrossRefGoogle Scholar
  49. 49.
    Yanai H, Hanauer S (2011) Assessing response and loss of response to biological therapies in IBD. Am J Gastroenterol 106:685–698PubMedCrossRefGoogle Scholar
  50. 50.
    Farrell RJ, Alsahli M, Jeen YT et al (2003) Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 124:917–924PubMedCrossRefGoogle Scholar
  51. 51.
    Vermeire S, Noman M, Van Assche G et al (2007) Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut 56:1226–1231PubMedCrossRefGoogle Scholar
  52. 52.
    Hanauer SB, Wagner CL, Bala M et al (2004) Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2:542–553PubMedCrossRefGoogle Scholar
  53. 53.
    Maser EA, Villela R, Silverberg MS et al (2006) Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol 4:1248–1254PubMedCrossRefGoogle Scholar
  54. 54.
    Reinisch W (2010) How to manage loss of response to anti-TNF in Crohn’s disease? Curr Drug Targets 11:152–155PubMedCrossRefGoogle Scholar
  55. 55.
    Seow CH, Newman A, Irwin SP et al (2010) Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 59:49–54PubMedCrossRefGoogle Scholar
  56. 56.
    Lee TW, Fedorak RN (2010) Tumor necrosis factor-α monoclonal antibodies in the treatment of inflammatory bowel disease: clinical practice pharmacology. Gastroenterol Clin North Am 39:543–557PubMedCrossRefGoogle Scholar
  57. 57.
    Sandborn WJ, Hanauer SB, Rutgeerts P et al (2007) Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut 56:1232–1239PubMedCrossRefGoogle Scholar
  58. 58.
    Kooloos WM, de Jong DJ, Huizinga TW, Guchelaar HJ (2007) Potential role of pharmacogenetics in anti-TNF treatment of rheumatoid arthritis and Crohn’s disease. Drug Discov Today 12:125–131PubMedCrossRefGoogle Scholar
  59. 59.
    De Nitto D, Sarra M, Cupi ML et al (2010) Targeting IL-23 and Th17-cytokines in inflammatory bowel diseases. Curr Pharm Des 16:3656–3660PubMedCrossRefGoogle Scholar
  60. 60.
    Biancheri P, Di Sabatino A, Snoek SA et al (2011) Effect of matrix metalloproteinase-3, -8, -10 and -12 on the structure and function of anti-tumor necrosis factor-α agents in inflammatory bowel disease. Dig Liver Dis 43:S132CrossRefGoogle Scholar
  61. 61.
    Meier J, Sturm A (2010) Concomitant use of immunomodulators with anti-TNF in Crohn’s disease: yes or no? Curr Drug Targets 11:176–178PubMedCrossRefGoogle Scholar
  62. 62.
    Lichtenstein GR, Diamond RH, Wagner CL et al (2009) Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 30:210–226PubMedCrossRefGoogle Scholar
  63. 63.
    Colombel JF, Sandborn WJ, Reinisch W et al (2010) Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 362:1383–1395PubMedCrossRefGoogle Scholar
  64. 64.
    Van Assche G, Magdelaine-Beuzelin C, D’Haens G et al (2008) Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology 134:1861–1868PubMedCrossRefGoogle Scholar
  65. 65.
    Toruner M, Loftus EV Jr, Harmsen WS (2008) Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 134:929–936PubMedCrossRefGoogle Scholar
  66. 66.
    Siegel CA, Marden SM, Persing SM et al (2009) Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn’s disease: a meta-analysis. Clin Gastroenterol Hepatol 7:874–881PubMedCrossRefGoogle Scholar
  67. 67.
    Moran G, Dillon J, Green J (2009) Crohn’s disease, hepatosplenic T-cell lymphoma and no biological therapy: are we barking up the wrong tree? Inflamm Bowel Dis 15:1281–1282PubMedCrossRefGoogle Scholar
  68. 68.
    Waugh AW, Garg S, Matic K et al (2010) Maintenance of clinical benefit in Crohn’s disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort. Aliment Pharmacol Ther 32:1129–1134PubMedCrossRefGoogle Scholar
  69. 69.
    Louis E, Vernier-Massouille G, Grimaud JC et al (2009) Infliximab discontinuation in Crohn’s disease patients in stable remission on combined therapy with immunosuppressors: a prospective ongoing cohort study. Gastroenterology 136:A146Google Scholar
  70. 70.
    Armuzzi A, De Vincentis F, Marzo M et al (2009) Long-term scheduled therapy with infliximab in inflammatory bowel disease. Gastroenterology 136:A663CrossRefGoogle Scholar
  71. 71.
    Oussalah A, Danese S, Peyrin-Biroulet L (2010) Efficacy of TNF antagonists beyond one year in adult and pediatric inflammatory bowel diseases: a systematic review. Curr Drug Targets 11:156–175PubMedCrossRefGoogle Scholar
  72. 72.
    Louis E, Belaiche J, Reenaers C (2010) Anti-TNF and Crohn’s disease: when should we stop? Curr Drug Targets 11:148–151PubMedCrossRefGoogle Scholar
  73. 73.
    Feagan BG, Bala M, Yan S et al (2005) Unemployment and disability in patients with moderately to severely active Crohn’s disease. J Clin Gastroenterol 39:390–395PubMedCrossRefGoogle Scholar
  74. 74.
    Blomqvist P, Ekborn A (1997) Inflammatory bowel diseases: health care and costs in Sweden in 1994. Scand J Gastroenterol 32:1134–1139PubMedCrossRefGoogle Scholar
  75. 75.
    Juan J, Estiarte R, Colomè E et al (2003) Burden of illness of Crohn’s disease in Spain. Dig Liver Dis 35:853–861PubMedCrossRefGoogle Scholar
  76. 76.
    Odes S (2006) Cost analysis and cost determinants in a European inflammatory bowel disease inception cohort with 10 years of follow-up evaluation. Gastroenterology 131:719–728PubMedCrossRefGoogle Scholar
  77. 77.
    Gibson PR, Weston AR, Shann A et al (2007) Relationship between disease severity, quality of life and health-care resource use in a cross-section of Australian patients with Crohn’s disease. J Gastroenterol Hepatol 22:1306–1312PubMedCrossRefGoogle Scholar
  78. 78.
    Odes S (2008) How expensive is inflammatory bowel disease? A critical analysis. World J Gastroenterol 14:6641–6647PubMedCrossRefGoogle Scholar
  79. 79.
    Bassi A, Dodd S, Williamson P et al (2004) Cost of illness of inflammatory bowel disease in the UK: a single centre retrospective study. Gut 53:1471–1478PubMedCrossRefGoogle Scholar
  80. 80.
    Bernstein CN, Papineau N, Zajaczkowski J et al (2000) Direct hospital costs for patients with inflammatory bowel disease in a Canadian tertiary care university hospital. Am J Gastroenterol 95:677–683PubMedCrossRefGoogle Scholar
  81. 81.
    van Langenberg DR, Simon SB, Holtmann GJ et al (2010) The burden of inpatients costs in inflammatory bowel disease and opportunities to optimize care: a single metropolitan Australian center experience. J Crohns Colitis 4:413–421PubMedCrossRefGoogle Scholar
  82. 82.
    Feagan BG, Vreeland MG, Larson LR et al (2000) Annual cost of care for Crohn’s disease: a payor perspective. Am J Gastroenterol 95:1955–1960PubMedCrossRefGoogle Scholar
  83. 83.
    Hay JW, Hay AR (1992) Inflammatory bowel disease: costs-of-illness. J Clin Gastroenterol 14:309–317PubMedCrossRefGoogle Scholar
  84. 84.
    Colombel JF, Sandborn WJ, Louis E et al (2011) Economic impact of deep remission in adalimumab-treated patients with Crohn’s disease: results from EXTEND. J Crohns Colitis 5:S41CrossRefGoogle Scholar
  85. 85.
    Hay AR, Hay JW (1992) Inflammatory bowel disease: medical costs algorithms. J Clin Gastroenterol 14:308–327Google Scholar
  86. 86.
    Dretzke J, Edlin R, Round J et al (2011) A systematic review and economic evaluation of the use of tumour necrosis factor-alpha (TNF-α) inhibitors, adalimumab and infliximab, for Crohn’s disease. Health Technol Assess 15:1–244PubMedGoogle Scholar
  87. 87.
    Lichtenstein GR, Yan S, Bala M et al (2004) Remission in patients with Crohn’s disease is associated with improvement in employment and quality of life and a decrease in hospitalization and surgeries. Am J Gastroenterol 99:91–96PubMedCrossRefGoogle Scholar
  88. 88.
    Feagan GB, Panaccione R, Sandborn WJ et al (2008) Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn’s disease: results from the CHARM study. Gastroenterology 135:1493–1499PubMedCrossRefGoogle Scholar
  89. 89.
    Jewell DP, Satsangi J, Lobo A et al (2005) Infliximab use in Crohn’s disease: impact on health care resources in the UK. Eur J Gastroenterol Hepatol 17:1047–1052PubMedCrossRefGoogle Scholar
  90. 90.
    Rubenstein JH, Chong RY, Cohen RD (2002) Infliximab decreases resource use among patients with Crohn’s disease. J Clin Gastroenterol 35:151–156PubMedCrossRefGoogle Scholar
  91. 91.
    Sprakes MB, Ford AC, Lisa W et al (2009) Infliximab therapy significantly reduces subsequent disease-related costs in Crohn’s disease patients: a 2-year follow-up study. Gastroenterology 136:A347–A348CrossRefGoogle Scholar
  92. 92.
    Clark W, Raftery J, Song F et al (2003) Systematic review and economic evaluation of the effectiveness of infliximab for the treatment of Crohn’s disease. Health Technol Assess 7:1–67PubMedGoogle Scholar
  93. 93.
    Marshall JK, Blackhouse G, Goeree R et al (2002) Infliximab for the treatment of Crohn’s disease: a systematic review and cost-utility analysis. Technology report no. 24. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); http://www.ccohta.ca
  94. 94.
    Jaisson-Hot I, Flourie B, Descos L et al (2004) Management for severe Crohn’s disease: a lifetime cost-utility analysis. Int J Technol Assess Health Care 20:274–279PubMedCrossRefGoogle Scholar
  95. 95.
    Bodger K, Kikuchi T, Hughes D (2009) Cost-effectiveness of biological therapy for Crohn’s disease: Markov cohort analyses incorporating United Kingdom patient-level cost data. Aliment Pharmacol Ther 30:165–174CrossRefGoogle Scholar
  96. 96.
    Lindsay J, Punekar YS, Morris J et al (2008) Health-economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn’s disease—modelling outcomes in active luminal and fistulizing disease in adults. Aliment Pharmacol Ther 28:76–87PubMedCrossRefGoogle Scholar
  97. 97.
    Loftus EV, Johnson SJ, Yu AP et al (2009) Cost-effectiveness of adalimumab for the maintenance of remission in patients with Crohn’s disease. Eur J Gastroenterol Hepatol 21:1302–1309PubMedCrossRefGoogle Scholar
  98. 98.
    Yu AP, Johnson S, Wang ST et al (2009) Cost utility of adalimumab versus infliximab maintenance therapies in the United States for moderately to severely active Crohn’s disease. Pharmacoeconomics 27:609–621PubMedCrossRefGoogle Scholar
  99. 99.
    Arseneau KO, Cohn SM, Cominelli F et al (2001) Cost-utility of initial medical management for Crohn’s disease perianal fistulae. Gastroenterology 120:1640–1656PubMedCrossRefGoogle Scholar
  100. 100.
    Marchetti M, Di Sabatino A, Liberato L et al (2011) Cost-effectiveness of top-down versus step-up strategies in patients with newly diagnosed active luminal Crohn’s disease. Dig Liver Dis 43:S133CrossRefGoogle Scholar
  101. 101.
    Bryan S, Andronis L, Hyde C et al (2010) Infliximab for the treatment of acute exacerbations of ulcerative colitis. Health Technol Assess 14:9–15PubMedGoogle Scholar
  102. 102.
    Tsai HH, Punekar YS, Morris J et al (2008) A model of the long-term cost-effectiveness of scheduled maintenance treatment with infliximab for moderate-to-severe ulcerative clitis. Aliment Pharmacol Ther 28:1230–1239PubMedCrossRefGoogle Scholar
  103. 103.
    Waljee AK, Morris AM, Waljee JF et al (2011) Individual health discount rate in patients with ulcerative colitis. Inflamm Bowel Dis 17:1328–1332PubMedCrossRefGoogle Scholar
  104. 104.
    Burger D, Travis S (2011) Conventional medical management of inflammatory bowel disease. Gastroenterology 140:1827–1837PubMedCrossRefGoogle Scholar
  105. 105.
    Peyrin-Biroulet L, Desreumaux P, Sandborn WJ, Colombel JF (2008) Crohn’s disease: beyond antagonists of tumour necrosis factor. Lancet 372:67–81PubMedCrossRefGoogle Scholar
  106. 106.
    Plevy SE, Targan SR (2011) Future therapeutic approaches for inflammatory bowel diseases. Gastroenterology 140:1838–1846PubMedCrossRefGoogle Scholar
  107. 107.
    Caprioli F, Pallone F, Monteleone G (2011) Cytokine therapies in Crohn’s disease: where are we now and where should we go? Inflamm Allergy Drug Targets 10:47–53PubMedGoogle Scholar
  108. 108.
    MacDonald TT (2010) Inside the microbial and immune labyrinth: totally gutted. Nat Med 16:1194–1195PubMedCrossRefGoogle Scholar

Copyright information

© SIMI 2011

Authors and Affiliations

  • Antonio Di Sabatino
    • 1
    • 2
  • Lucio Liberato
    • 1
  • Monia Marchetti
    • 1
  • Paolo Biancheri
    • 1
  • Gino R. Corazza
    • 1
  1. 1.First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche intestinali, Fondazione IRCCS Policlinico S. MatteoUniversity of PaviaPaviaItaly
  2. 2.Clinica Medica I, Fondazione IRCCS Policlinico San MatteoPaviaItaly

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