Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis

Choy MC1,2,3, Seah D1, Faleck DM4, Shah SC4,5, Chao CY6,7, An YK8, Radford-Smith G8, Bessissow T6, Dubinsky MC4, Ford AC9,10, Churilov L11, Yeomans ND3, De Cruz PP1,3. Inflamm Bowel Dis. 2019 Jan 3. doi: 10.1093/ibd/izy383. [Epub ahead of print]

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1 Department of Gastroenterology, Austin Hospital, Melbourne, Australia.

2 Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.

3 Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia.

4 The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

5 Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.

6 Division of Gastroenterology, McGill University, Montreal, Canada.

7 Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.

8 Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane Australia.

9 Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.

10 Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.

11 Statistics and Decision Analysis Academic Platform, Florey Institute of Neuroscience & Mental Health, The University of Melbourne, Melbourne, Australia.


BACKGROUND: Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.

METHODS: Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.

RESULTS: Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.

CONCLUSIONS: In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

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