UNASSIGNED: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them.
UNASSIGNED: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed.
UNASSIGNED: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54).
UNASSIGNED: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy.
To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC.
We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics.
From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction.
In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.

Pharmacokinetic data suggest that standard induction dosing schedules may not be sufficient in patients with acute severe colitis (ASUC). Hence, intensified induction regimes are increasingly used in the rescue treatment of hospitalized patients with ASUC to avoid the need for colectomy although the evidence for this is uncertain.
To conduct a systematic review of short- and long-term efficacy outcomes from accelerated infliximab induction studies.
Systematic search of relevant databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews) and relevant conference proceedings (Digestive Diseases Week, European Colitis and Crohn\'s Organisation Congress, United European Gastroenterology Week) was done.
We identified ten relevant studies with a total of 705 patients, of whom 308 received an intensified infliximab regime. Pooled analysis showed no difference in short-term or long-term colectomy rates in those receiving accelerated induction regimes when compared to standard induction. No significant differences in complication rates were identified.
The available uncontrolled studies so far do not suggest short-term or long-term benefit in using accelerated induction in hospitalized ASUC. The overall poor quality of available studies with confounding variables indicates the need for a randomized controlled trial with personalized risk stratification.

OBJECTIVE: Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect.
METHODS: We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods.
RESULTS: There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03).
CONCLUSIONS: In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.