Infliximab Induction Regimens in Steroid-Refractory Acute Severe Colitis

A Multicentre Retrospective Cohort Study With Propensity Score Analysis

Shaji Sebastian; Sally Myers; Konstantinos Argyriou; Gayle Martin; Louis Los; Joseph Fiske; Ravi Ranjan; Benjamin Cooper; Vivek Goodoory; Hey-Long Ching; NishaniLalanthika Jayasooriya; Johanne Brooks; Anjan Dhar; Achut H. Shenoy; Jimmy K. Limdi; Jeffrey Butterworth; Patrick B. Allen; Sunil Samuel; Gordon W. Moran; Richard Shenderey; Gareth Parkes; Alan Lobo; Nicholas A. Kennedy; Sreedar Subramanian; Tim Raine

Disclosures

Aliment Pharmacol Ther. 2019;50(6):330-335. 

In This Article

Materials and Methods

This was a multicentre retrospective cohort study. We included patients with ASUC meeting modified Truelove and Witt's criteria admitted between May 2016 and May 2018 for intravenous corticosteroids in 11 acute hospitals in the UK (Six University Teaching Hospitals and Five Peripheral Secondary Care Hospitals).

Inclusion and Exclusion Criteria

We included consecutive hospitalised patients needing intravenous steroids who received at least three doses of intravenous steroids. Physicians completing the case reports assessed them as meeting modified Truelove and Witt's criteria. We excluded patients with: a diagnosis of IBD unclassified, Crohn's colitis, infective colitis; coexistent cytomegalovirus; admission for elective surgery; and prior therapy with anti-TNF.

Study Design

Patients who received infliximab following failure of intravenous rescue therapy were stratified into two groups. The standard induction rescue group comprised of patients who received a dose of infliximab 5 mg/kg at week 0 and no further doses until 2 weeks after first dose. The accelerated induction group included patients who received at least two doses of 5 mg/kg with a second dose received on or before 7 days after the first dose and/or those who received 10 mg/kg for their first dose with a further dose within 2 weeks. We recorded available data on clinical and laboratory data at baseline, at commencement of rescue therapy, 30 days, 90 days, 6 months and 12 months.

Our primary outcome measure was colectomy rate at 30 days. Secondary outcome measures were index admission colectomy rates, colectomy rates at 90 days, 6 months and 12 months, the length of hospital admission and adverse events including post-operative complications and mortality.

Statistical Analysis

Continuous variables were summarised using mean and standard deviation and compared using Student's t test or the Mann-Whitney U test. Categorical variables were expressed as proportions and analysed by Fisher's exact test or chi-squared test as appropriate.

Propensity score-adjusted matching was used to minimise the possibility of provider bias in the choice of rescue treatment. Baseline clinical and demographic variables were matched in a 1:1 fashion to create a matched cohort with baseline variables which are independent of the initial infliximab dose. We ascribed a priori determined factors considered to affect the choice of rescue therapy including C-reactive Protein (CRP), serum albumin, CRP/albumin ratio, haemoglobin and the presence of pancolitis in the propensity score matching. Logistic regression was used to generate bivariate propensity scores using these variables. We used the greedy matching algorithm with the nearest calliper matching neighbour (random order) within a 0.01 propensity score selected for the best match in the matched cohort. We confirmed balanced covariates distribution after matching.

Kaplan-Meier survival curves were plotted for the primary outcome of 30-day colectomy rates in both unmatched and matched cohorts between those receiving standard induction compared to accelerated induction and the rates compared by log-rank statistic.

All tests were two-sided and a P value of <.05 was considered significant. We used SPSS statistics version 25 (IBM Corp.) for analysis.

As this was a retrospective data collection, in accordance with the UK Health Research Authority guidance, no central ethical committee submission was made. Individual institutions sought permissions to conduct a local service evaluation as appropriate.

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