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Published in: Digestive Diseases and Sciences 10/2018

01-10-2018 | Original Article

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

Authors: Amar Vedamurthy, Louise Xu, Jay Luther, Francis Colizzo, John J. Garber, Hamed Khalili, Ashwin N. Ananthakrishnan

Published in: Digestive Diseases and Sciences | Issue 10/2018

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Abstract

Background

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.

Aim

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

Methods

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.

Results

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).

Conclusion

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.
Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and outcome of acute severe colitis. J Crohn’s Colitis. 2010;4:431–437.CrossRef Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and outcome of acute severe colitis. J Crohn’s Colitis. 2010;4:431–437.CrossRef
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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. 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.
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.CrossRefPubMed Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.CrossRefPubMed
13.
go back to reference Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885.CrossRefPubMed Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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. 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.
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
25.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference 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. 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.
28.
go back to reference Steinhart AH, Baker JP, Brzezinski A, Prokipchuk EJ. Azathioprine therapy in chronic ulcerative colitis. J Clin Gastroenterol. 1990;12:271–275.CrossRefPubMed Steinhart AH, Baker JP, Brzezinski A, Prokipchuk EJ. Azathioprine therapy in chronic ulcerative colitis. J Clin Gastroenterol. 1990;12:271–275.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
31.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
32.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Long-Term Outcomes of Immunosuppression-Naïve Steroid Responders Following Hospitalization for Ulcerative Colitis
Authors
Amar Vedamurthy
Louise Xu
Jay Luther
Francis Colizzo
John J. Garber
Hamed Khalili
Ashwin N. Ananthakrishnan
Publication date
01-10-2018
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 10/2018
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5176-3

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