International Journal of Colorectal Disease

, Volume 29, Issue 11, pp 1329–1338 | Cite as

How fast up the ladder? Factors associated with immunosuppressive or anti-TNF therapies in IBD patients at early stages: results from a population-based cohort

  • Claudia Ott
  • Angela Takses
  • Florian Obermeier
  • Elisabeth Schnoy
  • Bernd Salzberger
  • Martina Müller
Original Article



With the introduction of anti-TNF therapies in the treatment of IBD, the therapeutic strategies have changed to an accelerated step-up care to avoid long-term complications. Little is known about the implementation of these strategies into daily care. We aimed to evaluate this question and to identify factors associated with the early use of immunosuppressants or anti-TNF therapies in a population-based IBD cohort.


Patients with an IBD diagnosed between January 2004 and December 2008 were included. Medical therapies were evaluated at first diagnosis and during a 5-year follow-up. Risk factors associated with the initiation of an immunosuppressive therapy were assessed.


Two hundred and forty-one patients were evaluated (145 Crohn’s disease (CD), 96 ulcerative colitis (UC)). An immunosuppressive or anti-TNF therapy was started in 83 CD (57.2 %) and 40 UC (43 %) patients (p = 0.033, relative risks (RR) 1.77; 95 % confidence interval (CI) 1.05–3.0). After 5 years, 38.8 % CD patients on immunosuppressive therapy were treated with anti-TNF therapies. The use of corticosteroids at first diagnosis, disease localization and surgery were independent predictors for an immunosuppressive or anti-TNF therapy in CD. In UC, the extension of disease was associated with immunosuppressive therapies. The use of steroids and localization in CD patients and an extended disease in UC patients affected the time until an immunosuppressive therapy was started.


We found a high proportion of patients using an immunosuppressive therapy during the early course. Therefore, the accelerated step-up strategy seems to be successfully implemented in the daily care of IBD patients. We were able to identify several factors associated with an immunosuppressive or anti-TNF therapy in CD and UC.


Crohn’s disease Ulcerative colitis Accelerated step-up Immunosuppressive therapy Azathioprine Anti-TNF therapy 


  1. 1.
    Cosnes J, Gower-Rousseau C, Seksik P, Cortot A (2011) Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 140(6):1785–1794PubMedCrossRefGoogle Scholar
  2. 2.
    Hanauer SB, Present DH (2003) The state of the art in the management of inflammatory bowel disease. Rev Gastroenterol Disord 3(2):81–92PubMedGoogle Scholar
  3. 3.
    Lowenberg M, D’Haens G (2012) Mucosal healing in Crohn’s disease: relevance for clinical outcomes. Curr Drug Targets 13(10):1248–1251PubMedCrossRefGoogle Scholar
  4. 4.
    Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, Stokkers P, Hommes D, Rutgeerts P, Vermeire S et al.(2010) Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology, 138(2):463–468; quiz e410-461.Google Scholar
  5. 5.
    Panaccione R, Rutgeerts P, Sandborn WJ, Feagan B, Schreiber S, Ghosh S (2008) Review article: treatment algorithms to maximize remission and minimize corticosteroid dependence in patients with inflammatory bowel disease. Aliment Pharmacol Ther 28(6):674–688PubMedCrossRefGoogle Scholar
  6. 6.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR et al (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353(23):2462–2476PubMedCrossRefGoogle Scholar
  7. 7.
    Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W et al (2002) Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 359(9317):1541–1549PubMedCrossRefGoogle Scholar
  8. 8.
    Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, Schreiber S, Byczkowski D, Li J, Kent JD et al (2007) Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 132(1):52–65PubMedCrossRefGoogle Scholar
  9. 9.
    Schreiber S, Reinisch W, Colombel JF, Sandborn WJ, Hommes DW, Robinson AM, Huang B, Lomax KG, Pollack PF (2013) Subgroup analysis of the placebo-controlled CHARM trial: increased remission rates through 3 years for adalimumab-treated patients with early Crohn’s disease. J Crohn’s Colitis 7(3):213–221CrossRefGoogle Scholar
  10. 10.
    Schreiber S, Colombel JF, Bloomfield R, Nikolaus S, Scholmerich J, Panes J, Sandborn WJ (2010) Increased response and remission rates in short-duration Crohn’s disease with subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol 105(7):1574–1582PubMedCrossRefGoogle Scholar
  11. 11.
    D’Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A et al (2008) Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 371(9613):660–667PubMedCrossRefGoogle Scholar
  12. 12.
    Solberg IC, Lygren I, Jahnsen J, Aadland E, Hoie O, Cvancarova M, Bernklev T, Henriksen M, Sauar J, Vatn MH et al (2009) Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol 44(4):431–440PubMedCrossRefGoogle Scholar
  13. 13.
    Solberg IC, Vatn MH, Hoie O, Stray N, Sauar J, Jahnsen J, Moum B, Lygren I (2007) Clinical course in Crohn’s disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol 5(12):1430–1438PubMedCrossRefGoogle Scholar
  14. 14.
    Cosnes J, Bourrier A, Nion-Larmurier I, Sokol H, Beaugerie L, Seksik P (2012) Factors affecting outcomes in Crohn’s disease over 15 years. Gut 61(8):1140–1145PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Burger D, Travis S (2011) Conventional medical management of inflammatory bowel disease. Gastroenterology, 140(6):1827–1837 e1822.Google Scholar
  16. 16.
    Sands BE (2012) The risks and benefits of early immunosuppression and biological therapy. Dig Dis 30(Suppl 3):100–106PubMedCrossRefGoogle Scholar
  17. 17.
    Ordas I, Feagan BG, Sandborn WJ (2011) Early use of immunosuppressives or TNF antagonists for the treatment of Crohn’s disease: time for a change. Gut 60(12):1754–1763PubMedCrossRefGoogle Scholar
  18. 18.
    Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosnes J (2006) Predictors of Crohn’s disease. Gastroenterology 130(3):650–656PubMedCrossRefGoogle Scholar
  19. 19.
    Lakatos PL, Czegledi Z, Szamosi T, Banai J, David G, Zsigmond F, Pandur T, Erdelyi Z, Gemela O, Papp J et al (2009) Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease. World J Gastroenterol 15(28):3504–3510PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Loly C, Belaiche J, Louis E (2008) Predictors of severe Crohn’s disease. Scand J Gastroenterol 43(8):948–954PubMedCrossRefGoogle Scholar
  21. 21.
    Romberg-Camps MJ, Dagnelie PC, Kester AD, de Kruijs MA H-v, Cilissen M, Engels LG, Van Deursen C, Hameeteman WH, Wolters FL, Russel MG et al (2009) Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease. Am J Gastroenterol 104(2):371–383PubMedCrossRefGoogle Scholar
  22. 22.
    Wolters FL, Russel MG, Sijbrandij J, Ambergen T, Odes S, Riis L, Langholz E, Politi P, Qasim A, Koutroubakis I et al (2006) Phenotype at diagnosis predicts recurrence rates in Crohn’s disease. Gut 55(8):1124–1130PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Thia KT, Sandborn WJ, Harmsen WS, Zinsmeister AR, Loftus EV Jr (2010) Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort. Gastroenterology 139(4):1147–1155PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Roth LS, Chande N, Ponich T, Roth ML, Gregor J (2010) Predictors of disease severity in ulcerative colitis patients from Southwestern Ontario. World J Gastroenterol 16(2):232–236PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Hoie O, Wolters F, Riis L, Aamodt G, Solberg C, Bernklev T, Odes S, Mouzas IA, Beltrami M, Langholz E et al (2007) Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide population-based cohort. Am J Gastroenterol 102(8):1692–1701PubMedCrossRefGoogle Scholar
  26. 26.
    Ott C, Obermeier F, Thieler S, Kemptner D, Bauer A, Scholmerich J, Rogler G, Timmer A (2008) The incidence of inflammatory bowel disease in a rural region of Southern Germany: a prospective population-based study. Eur J Gastroenterol Hepatol 20(9):917–923PubMedCrossRefGoogle Scholar
  27. 27.
    Gasche C, Scholmerich J, Brynskov J, D’Haens G, Hanauer SB, Irvine EJ, Jewell DP, Rachmilewitz D, Sachar DB, Sandborn WJ et al (2000) A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 6(1):8–15PubMedCrossRefGoogle Scholar
  28. 28.
    Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, D’Haens G, D’Hoore A, Mantzaris G, Novacek G et al (2012) Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohn’s Colitis 6(10):991–1030CrossRefGoogle Scholar
  29. 29.
    Dignass A, Preiss JC, Aust DE, Autschbach F, Ballauff A, Barretton G, Bokemeyer B, Fichtner-Feigl S, Hagel S, Herrlinger KR et al (2011) Updated German guideline on diagnosis and treatment of ulcerative colitis, 2011. Z Gastroenterol 49(9):1276–1341PubMedCrossRefGoogle Scholar
  30. 30.
    Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, Danese S, D’Hoore A, Gassull M, Gomollon F et al (2010) The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohn’s Colitis 4(1):28–62CrossRefGoogle Scholar
  31. 31.
    Hoffmann JC, Preiss JC, Autschbach F, Buhr HJ, Hauser W, Herrlinger K, Hohne W, Koletzko S, Krieglstein CF, Kruis W et al (2008) Clinical practice guideline on diagnosis and treatment of Crohn’s disease. Z Gastroenterol 46(9):1094–1146PubMedCrossRefGoogle Scholar
  32. 32.
    Lakatos PL, Golovics PA, David G, Pandur T, Erdelyi Z, Horvath A, Mester G, Balogh M, Szipocs I, Molnar C et al (2012) Has there been a change in the natural history of Crohn’s disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977–2009. Am J Gastroenterol 107(4):579–588PubMedCrossRefGoogle Scholar
  33. 33.
    Jess T, Riis L, Vind I, Winther KV, Borg S, Binder V, Langholz E, Thomsen OO, Munkholm P (2007) Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm Bowel Dis 13(4):481–489PubMedCrossRefGoogle Scholar
  34. 34.
    Mossop H, Davies P, Murphy MS (2008) Predicting the need for azathioprine at first presentation in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 47(2):123–129PubMedCrossRefGoogle Scholar
  35. 35.
    Chow DK, Sung JJ, Wu JC, Tsoi KK, Leong RW, Chan FK (2009) Upper gastrointestinal tract phenotype of Crohn’s disease is associated with early surgery and further hospitalization. Inflamm Bowel Dis 15(4):551–557PubMedCrossRefGoogle Scholar
  36. 36.
    Lau A, Chande N, Ponich T, Gregor JC (2008) Predictive factors associated with immunosuppressive agent use in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 28(5):606–613PubMedCrossRefGoogle Scholar
  37. 37.
    Szamosi T, Banai J, Lakatos L, Czegledi Z, David G, Zsigmond F, Pandur T, Erdelyi Z, Gemela O, Papp M et al (2010) Early azathioprine/biological therapy is associated with decreased risk for first surgery and delays time to surgery but not reoperation in both smokers and nonsmokers with Crohn’s disease, while smoking decreases the risk of colectomy in ulcerative colitis. Eur J Gastroenterol Hepatol 22(7):872–879PubMedCrossRefGoogle Scholar
  38. 38.
    Rubin DT, Uluscu O, Sederman R (2012) Response to biologic therapy in Crohn’s disease is improved with early treatment: an analysis of health claims data. Inflamm Bowel Dis 18(12):2225–2231PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Claudia Ott
    • 1
  • Angela Takses
    • 1
  • Florian Obermeier
    • 1
  • Elisabeth Schnoy
    • 1
  • Bernd Salzberger
    • 1
  • Martina Müller
    • 1
  1. 1.Department of Internal Medicine IUniversity of RegensburgRegensburgGermany

Personalised recommendations