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

Abstract

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.

Keywords: acute severe ulcerative colitis; colectomy; infliximab.

FIGURE 1.

PRISMA flowchart.

FIGURE 2.

Forest plot using random-effects model for overall pooled colectomy-free survival (proportions).

FIGURE 2.

Forest plot using random-effects model for overall pooled colectomy-free survival (proportions).

FIGURE 3.

Forest plot using random-effects models assessing CFS at month 1, 3, and 12 for (A) 5-mg/kg multiple-dose vs 5-mg/kg single-dose induction and (B) dose-intensified vs 5-mg/kg standard-schedule induction.

FIGURE 4.

Forest plot using random-effects model to assess mean differences in covariates between dose-intensified and 5-mg/kg standard-schedule cohorts.