Digestive Diseases and Sciences

, Volume 63, Issue 10, pp 2740–2746 | Cite as

Long-Term Outcomes of Immunosuppression-Naïve Steroid Responders Following Hospitalization for Ulcerative Colitis

  • Amar Vedamurthy
  • Louise Xu
  • Jay Luther
  • Francis Colizzo
  • John J. Garber
  • Hamed Khalili
  • Ashwin N. AnanthakrishnanEmail author
Original Article



Requirement for hospitalization in ulcerative colitis (UC) is a marker of severity of disease. However, the paradigm of when to escalate therapy in such patients and the benefits of early immunomodulator initiation is less well established.


To examine the benefits of early therapy escalation in immunosuppression-naïve patients hospitalized with severe ulcerative colitis responsive to steroids.


We identified hospitalized UC patients who were immunosuppression naïve at index hospitalization and responded to intravenous steroids, not requiring medical or surgical rescue therapy. The ‘therapy escalated’ group comprised of those who were initiated on immunomodulators within 3 months of hospitalization. The need for colectomy at 12 months was compared to the ‘not escalated’ group who remained on non-immunosuppressive therapy.


Among 133 immunosuppressive naïve patients hospitalized for ulcerative colitis, 13 (9.8%) who responded to intravenous steroids and did not require rescue therapy underwent colectomy by 1 year. Among 123 patients who escalated to either immunomodulators (n = 46, 37%) or remained on non-immunosuppressive therapy (92% on 5-ASA), there was no difference in the need for colectomy at 1 year (10.8 vs. 7.8%; multivariate OR 1.29, 95% CI 0.35–4.74). There was also no difference in the time to colectomy between the two groups (p = 0.55).


Immunosuppression-naïve ASUC patients who respond to intravenous steroids remain at risk for colectomy. Immunomodulator initiation by 3 months did not reduce risk of colectomy at 1 year. There is an important need for prospective studies identifying thresholds for therapy escalation in UC.


Hospitalization Colectomy Steroids Acute severe ulcerative colitis 


Author’s contributions

AV contributed to study design, data extraction and statistical analysis, drafting of the manuscript, and approval of the final manuscript. LX extracted the data and approved the final manuscript. JL, JJG, FC, HK approved the final manuscript. ANA was involved in study design and supervision, statistical analysis, drafting of the manuscript, and approval of the final manuscript.


Ananthakrishnan is supported in part by grants from the National Institutes of Health (R03 DK112909) and the Crohn’s and Colitis Foundation.

Compliance with ethical standards

Conflict of interest

Ananthakrishnan has served on scientific advisory boards for Abbvie, Takeda, Gilead, and Merck and has received research support from Pfizer.


  1. 1.
    Bernstein CN, Wajda A, Svenson L, et al. The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am J Gastroenterol. 2006;101:1559.CrossRefPubMedGoogle Scholar
  2. 2.
    Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and outcome of acute severe colitis. J Crohn’s Colitis. 2010;4:431–437.CrossRefGoogle Scholar
  3. 3.
    Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2:1041–1048.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Turner D, Walsh CM, Steinhart AH, Griffiths AM. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5:103–110.CrossRefPubMedGoogle Scholar
  5. 5.
    Aratari A, Papi C, Clemente V, et al. Colectomy rate in acute severe ulcerative colitis in the infliximab era. Dig Liver Dis. 2008;40:821–826.CrossRefPubMedGoogle Scholar
  6. 6.
    Ho GT, Chiam P, Drummond H, Loane J, Arnott ID, Satsangi J. The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort. Aliment Pharmacol Ther. 2006;24:319–330.CrossRefPubMedGoogle Scholar
  7. 7.
    Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–1845.CrossRefPubMedGoogle Scholar
  8. 8.
    Arts J, D’Haens G, Zeegers M, et al. Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis. Inflamm Bowel Dis. 2004;10:73–78.CrossRefPubMedGoogle Scholar
  9. 9.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.CrossRefPubMedGoogle Scholar
  10. 10.
    Sandborn W, van Assche G, Reinisch W. Adalimumab in the treatment of moderate-to-severe ulcerative colitis: ULTRA 2 trial results. Gastroenterol Hepatol (N Y). 2013;9:317–320.Google Scholar
  11. 11.
    Panccione R, Ghosh S, Middleton S, et al. Infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis: the UC success trial. Gastroenterology. 2011;140:134.CrossRefGoogle Scholar
  12. 12.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.CrossRefPubMedGoogle Scholar
  13. 13.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885.CrossRefPubMedGoogle Scholar
  14. 14.
    Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology. 1999;117:761–769.CrossRefPubMedGoogle Scholar
  15. 15.
    Sipponen T, Savilahti E, Kärkkäinen P, et al. Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti-TNF-alpha therapy for Crohn’s disease. Inflamm Bowel Dis. 2008;14:1392–1398.CrossRefPubMedGoogle Scholar
  16. 16.
    Bouguen G, Levesque BG, Feagan BG, et al. Treat to Target: A Proposed New Paradigm for the Management of Crohn’s Disease. Clin Gastroenterol Hepatol. 2015;13:1042–1050.e1042.CrossRefPubMedGoogle Scholar
  17. 17.
    D’Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet. 2008;371:660–667.CrossRefPubMedGoogle Scholar
  18. 18.
    Khanna R, Bressler B, Levesque BG, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet. 2015;386:1825–1834.CrossRefPubMedGoogle Scholar
  19. 19.
    Bojic D, Radojicic Z, Nedeljkovic-Protic M, Al-Ali M, Jewell DP, Travis SP. Long-term outcome after admission for acute severe ulcerative colitis in Oxford: the 1992–1993 cohort. Inflamm Bowel Dis. 2009;15:823–828.CrossRefPubMedGoogle Scholar
  20. 20.
    Ananthakrishnan AN, Issa M, Beaulieu DB, et al. History of medical hospitalization predicts future need for colectomy in patients with ulcerative colitis. Inflamm Bowel Dis. 2009;15:176–181.CrossRefPubMedGoogle Scholar
  21. 21.
    Nalichowski R, Keogh D, Chueh HC, Murphy SN. Calculating the benefits of a Research Patient Data Repository. In: AMIA Annual Symposium Proceedings AMIA Symposium; 2006:1044.Google Scholar
  22. 22.
    Lee HS, Yang SK, Soh JS, et al. Short- and long-term outcomes of acute severe ulcerative colitis in Korea: the 1999–2005 cohort. Inflamm Bowel Dis. 2015;21:1825–1831.CrossRefPubMedGoogle Scholar
  23. 23.
    Jain S, Kedia S, Sethi T, et al. Predictors of long-term outcomes in patients with acute severe colitis: a Northern Indian cohort study. J Gastroenterol Hepatol. 2018;33:615–622.CrossRefPubMedGoogle Scholar
  24. 24.
    Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006;55:47–53.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hawthorne AB, Logan RF, Hawkey CJ, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ (Clin Res Ed). 1992;305:20–22.CrossRefGoogle Scholar
  26. 26.
    Jewell DP, Truelove SC. Azathioprine in ulcerative colitis: final report on controlled therapeutic trial. Br Med J. 1974;4:627–630.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Sood A, Midha V, Sood N, Avasthi G. Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis. Ind J Gastroenterol. 2003;22:79–81.Google Scholar
  28. 28.
    Steinhart AH, Baker JP, Brzezinski A, Prokipchuk EJ. Azathioprine therapy in chronic ulcerative colitis. J Clin Gastroenterol. 1990;12:271–275.CrossRefPubMedGoogle Scholar
  29. 29.
    Carbonnel F, Colombel JF, Filippi J, et al. Methotrexate is not superior to placebo for inducing steroid-free remission, but induces steroid-free clinical remission in a larger proportion of patients with ulcerative colitis. Gastroenterology. 2016;150:380–388.e384.CrossRefPubMedGoogle Scholar
  30. 30.
    Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. Gastroenterology. 1996;110:1416–1421.CrossRefPubMedGoogle Scholar
  31. 31.
    Solberg IC, Lygren I, Jahnsen J, 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;44:431–440.CrossRefPubMedGoogle Scholar
  32. 32.
    Solberg IC, Vatn MH, Hoie O, et al. Clinical course in Crohn’s disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol. 2007;5:1430–1438.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Amar Vedamurthy
    • 1
  • Louise Xu
    • 2
  • Jay Luther
    • 3
  • Francis Colizzo
    • 3
  • John J. Garber
    • 3
  • Hamed Khalili
    • 3
  • Ashwin N. Ananthakrishnan
    • 3
    • 4
    Email author
  1. 1.Department of Hospital MedicineMassachusetts General HospitalBostonUSA
  2. 2.Department of MedicineMassachusetts General HospitalBostonUSA
  3. 3.Division of GastroenterologyMassachusetts General HospitalBostonUSA
  4. 4.Massachusetts General Hospital Crohn’s and Colitis CentreBostonUSA

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