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

Narula N1, Fine M, Colombel JF, Marshall JK, Reinisch W. Inflamm Bowel Dis. 2015 Apr 1. [Epub ahead of print]
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1*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.


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.

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