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Systematic Review: Sequential Rescue Therapy in Severe Ulcerative Colitis Do the Benefits Outweigh the Risks?

Narula, Neeraj MD*,†; Fine, Michael MD*; Colombel, Jean-Frederic MD, PhD; Marshall, John K. MD, MSc*; Reinisch, Walter MD, PhD*

doi: 10.1097/MIB.0000000000000350
Clinical Review Articles

Background: The options for medical management of acute severe steroid-refractory ulcerative colitis (UC) are limited. Recent guidelines recommend against use of sequential rescue therapy in the setting of failed medical management with initial salvage therapy. A systematic review was conducted to assess outcomes of sequential rescue therapy with infliximab (IFX) and calcineurin inhibitors like cyclosporine (CsA) or tacrolimus (Tac) in patients with steroid-refractory UC.

Methods: A literature search identified studies that investigated treatment with IFX and CsA or Tac in acute severe UC. Outcomes of interest included short-term symptomatic response to treatment, rates of remission, adverse drug reactions, serious infections, mortality, and colectomy at 3 and 12 months.

Results: Overall, ten studies with 314 participants were eligible for inclusion. After sequential treatment, patients achieved short-term treatment response in 62.4% (95% confidence interval [CI], 57.0%–67.8%) of cases and remission in 38.9% (95% CI, 33.5%–44.3%). Colectomy rates were 28.3% (95% CI, 21.7%–34.5%) at 3 months and 42.3% (95% CI, 36.0%–48.6%) at 12 months. Adverse events were encountered by 23.0% (95% CI, 17.7%–28.3%) of patients, including serious infections in 6.7% (95% CI, 3.6%–9.8%) and mortality in 1% (95% CI, 0%–2.1%).

Conclusions: The risk of sequential therapy in steroid-refractory UC seems lower than initially reported. Caution must be exercised however because of very low-quality evidence. In contrast to recent guidelines, the current analysis does not support a decision for or against use of sequential rescue therapy, which should only be performed at specialized referral centers familiar with the use of calcineurin inhibition.

Article first published online 1 April 2015.Supplemental Digital Content is Available in the Text.

*Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada; and

Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai Hospital, New York, New York.

Reprints: Neeraj Narula, MD, Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, One Gustave L. Levy Place, Box 1069, New York, NY 10029 (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

W. Reinisch has served as a speaker, a consultant, and/or an advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM-Pharma, Aptalis, Astellas, AstraZeneca, Avaxia, BioClinica, Biogen Idec, Bristol-Myers Squibb, Cellerix, Chemo-Centryx, Celgene, Centocor, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grünenthal, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trials, Schering-Plough, Setpoint Medical, Shire, Takeda, Therakos, TiGenix, UCB, Vifor, Yakult, Zyngenia, and 4SC. J-F. Colombel has served as a consultant, an advisory board member, or a speaker for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Ferring, Genentech, Giuliani SPA, Merck & Co., Mitsubishi, Nestle Nutrition Science Partners Ltd., Pfizer Inc., Prometheus Laboratories, Receptos, Takeda/Millennium Pharmaceuticals Inc., UCB Pharma, Vertex, and Dr. August Wolff GmbH & Co. J. K. Marshall has served as a consultant, an advisory board member, or a speaker for AbbVie, Aptalis, AstraZeneca, Celltrion, Cubist, Ferring, Forest, Janssen, Optimer, Procter & Gamble, Shire, Takeda, and Warner Chilcott. The remaining authors have no conflicts of interest to disclose.

Received December 10, 2014

Accepted January 22, 2015

© Crohn's & Colitis Foundation of America, Inc.
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