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

Abstract

BackgroundInfliximab 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.MethodsStudies 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.ResultsForty-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.ConclusionsIn 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.

Letter: should we intensify infliximab in acute severe ulcerative colitis? Author's reply

“…Furthermore, the need for earlier prediction models is highlighted by the varying practices in relation to timing and selection of patients for rescue therapies. 5 I also agree with Drs. Laharie and Riviere on the lack of evidence for proposing accelerated induction regimens in ASUC as seen in the two recent updated meta-analyses of observational studies.…”

“…6,7 Nevertheless, the recently published UK IBD guidelines 8 recommend its use in this setting and, based on national surveys, the use of accelerated induction is frequent. 5,9 The ongoing prospective studies may provide us with more robust evidence to settle this important debate.Until then, physicians should use their judgement based on available risk prediction models and involve patients and colorectal surgeons in shared decision-making when choosing their treatment approach.…”

Editorial: accelerated infliximab induction—it's time to settle the debate! Authors' reply

“…We also agree that almost all of the cohort studies so far have not reported data to support the use of accelerated induction dosing regimens despite compelling pharmacokinetic and pharmacodynamic data. 3 In the recent systematic review from Choy et al, 4 while multiple dosing of infliximab was better than a single dose in reducing colectomy, there was no benefit in any of the intensive dosing regimes (more frequent doses of 5 mg/kg or higher front loading dose of 10 mg/kg) in short-term or long-term colectomy rates. This is similar to the findings from our own meta-analysis which failed to show a benefit from intensified dosing.…”

Letter: infliximab induction regimens in steroid‐refractory acute severe colitis—a propensity score analysis

“…In particular no significant difference in early or late colectomy rates has been found between accelerated and standard regimens in two recent systematic reviews. 2,3 Clinicians' perception of disease severity often drives the selection of standard vs accelerated therapy. Sebastian et al 1 are to be commended for their use of propensity scoring analysis in their study as a means of addressing provider bias.…”