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.
*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: firstname.lastname@example.org).
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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