Baseline infliximab (IFX) clearance is a strong predictive factor for colectomy in hospitalized patients with acute severe ulcerative colitis (ASUC) receiving IFX salvage therapy, according to findings published in Clinical Gastroenterology and Hepatology.
Approximately 30% of patients with ASUC fail therapy, and short-term colectomy rates range from 0% to 50% in this population. While IFX is an effective induction and maintenance therapy for ulcerative colitis (UC), the optimal IFX dosing for salvage therapy in hospitalized patients with ASUC remains unclear. In this study, researchers evaluated the relationship between induction IFX drug clearance and colectomy rates.
The researchers obtained retrospective data on hospitalized patients with ASUC from records at the University of California, San Diego (UCSD). Inclusion criteria comprised adults aged >18 years who had been diagnosed with UC from July 2014-May 2018 and started IFX as rescue therapy for ASUC. The researchers calculated baseline IFX drug clearance based on an existing formula in these patients. The primary objective was to compare clearance between patients who required colectomy after 6 months and patients who did not require colectomy. The researchers also evaluated the requirement for rehospitalization related to UC disease activity within 6 months of initial hospitalization. Statistical analyses included receiver operating characteristic curve (AUROC) to evaluate clearance thresholds for colectomy and multivariable logistic regression to assess factors associated with colectomy.
Of the 39 patients with ASUC, median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in those who did not require colectomy (0.733 vs 0.569 L/day; P =.005). IFX clearance had excellent diagnostic accuracy to colectomy. AUROC analysis demonstrated an IFX clearance threshold of 0.627 L/day or higher and had 80.0% sensitivity and 82.8% specificity to predict requirement of colectomy at 6 months (AUC=0.80; 95% CI, 0.64-0.96). Moreover, patients with a clearance of 0.627L/day or greater had higher rates of colectomy at 6 months (61.5% vs. 7.7%, P =.001). Similar results were observed at 30 days and 1 year compared with patients with lower clearance. Multivariable analysis revealed baseline IFX clearance to be the only factor associated with colectomy. Lastly, IFX dose in hospital was higher in patients who required colectomy, with similar results observed at 30 days and 1 year.
Limitations of the study include its retrospective design, small sample size, and the possibility that existing models may not be fully adequate in predicting the doses required to achieve adequate trough concentrations in ASUC.
The researchers concluded that higher values of calculated infliximab clearance before infliximab administration are related to higher rates of colectomy in patients hospitalized with ASUC. Future studies using IFX pharmacokinetic models for ASUC patients to allow comparative trials on clearance-based vs standard dosing are recommended.
Battat R, Hemperly A, Truong S, Whitmire N, Boland BS, Dulai PS et al. Baseline clearance of infliximab is associated with requirement for colectomy in patients with acute severe ulcerative colitis (published online April 26, 2020). Clin Gastroenterol Hepatol. doi.org/10.1016/j.cgh.2020.03.072.