Personalized infliximab rescue therapy to maximize colectomy-free survival in patients with acute severe ulcerative colitis
(2026) Journal of Crohn’s and Colitis — Vol. 20, n° 3, p. jjag029 (2026)
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- Authors
Hoffert, Yannick 
Afif, Waqqas Pedicelli, Alessandro Dreesen, Erwin
- Abstract
- Background & Aims: Infliximab is an established rescue therapy for patients with steroid-refractory acute severe ulcerative colitis (ASUC), yet optimal dosing strategies minimizing colectomy risk remain unclear. We aimed to develop a model-informed risk stratification algorithm to identify patients at high risk of colectomy within 90 days of initiating infliximab to support personalized dosing. Methods: We conducted a multicenter, retrospective population pharmacokinetics (popPK) and exposure-response study using data from patients with ASUC. A parametric time-to-event model was developed to characterize the 90-day colectomy risk. Patient characteristics and pharmacokinetic projections were evaluated as predictors. These modelling results informed the development of an algorithm for risk stratification and personalized infliximab rescue dosing. Results: Seven medical centers contributed data from 72 patients with ASUC, yielding a total of 152 infliximab serum concentrations. Eleven patients underwent colectomy within 90 days. The strongest predictor of colectomy was the clearance-normalized exposure between weeks 2 and 4 (area under the concentration-time curve, AUC w2-4 to Bayesian-forecasted infliximab clearance, CL), with an area under the receiver operating characteristic curve of 0.79 (95% confidence interval [CI], 0.52-1.00). The AUC w2-4 /CL ratio was calculated by individualizing the popPK model using the patient's body weight, baseline C-reactive protein, and infliximab concentrations. Patients with a log-transformed AUC w2-4 /CL ratio < 5.79 were classified as high risk for colectomy (sensitivity 83%, specificity 85%). Overall classification accuracy was 85% (95% CI, 74-92). Conclusions: We developed a model-based dose-exposure-response framework to predict colectomy risk in ASUC. We integrated the algorithm into an interactive tool to enable individualized infliximab rescue therapy.
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Citations
Niyigena, E., Hoffert, Y., Afif, W., Pedicelli, A., Roblin, X., Hanžel, J., Papamichael, K., Kobayashi, T., Elens, L., Wang, Z., Ferrante, M., Verstockt, B., Vermeire, S., Vande Casteele, N., Battat, R., & Dreesen, E. (2026). Personalized infliximab rescue therapy to maximize colectomy-free survival in patients with acute severe ulcerative colitis. Journal of Crohn’s and Colitis, 20(3), jjag029. https://doi.org/10.1093/ecco-jcc/jjag029 (Original work published 2026)