Data presented at the 20th Congress of ECCO, February 19–22, 2025 (Berlin, Germany), from a study conducted by researchers from Freie Universität Berlin, Rigshospitalet, Herlev Hospital, and Odense University Hospital, provide evidence that patients who are hospitalized with severe ulcerative colitis (UC) may experience significantly increased infliximab clearance, leading to reduced drug exposure when standard dosing regimens are used.1 These findings suggest that an intensified treatment approach, guided by therapeutic drug monitoring (TDM) and pharmacokinetic (PK) modeling, may be necessary to optimize outcomes in these patients.
The study included infliximab concentration data from 154 patients with UC, comprising 248 induction-phase and 58 maintenance-phase samples. A non-linear mixed-effects PK model was developed to assess infliximab clearance, incorporating testing for a range of variables including clinical disease activity scores, endoscopic findings, CRP, albumin levels and hospitalization status.
A two-compartment model with linear clearance was found to describe infliximab PK in-line with previously known data. Upon analysis of the data hospitalization emerged as the most significant factor affecting infliximab clearance, with patients who were hospitalized (32% of the study population) exhibiting a 35% [90%CI 14-56%] higher clearance rate compared to outpatients (0.463 L/day vs. 0.339 L/day, p<0.0001). This accelerated clearance led to a marked reduction in infliximab exposure from week 2, with:
- 74% of patients who were hospitalized having subtherapeutic infliximab concentrations at week 2 (<20 µg/mL)
- 69% at week 6 (<15 µg/mL)
- 56% at week 14 (<7 µg/mL)
Further analysis showed that formal fulfilment of Truelove Witt’s criteria for acute severe ulcerative colitis (ASUC) did not lead to an additional increase in infliximab clearance (median clearance of 0.442 L/day in ASUC patients vs. 0.516 L/day in non-ASUC, p=0.08). Additionally, incorporating albumin levels into the model was not reported to significantly improve its predictive accuracy.
Concluding the results, the study investigators emphasized that infliximab clearance is significantly higher in hospitalized patients with severe UC, resulting in a high prevalence of underexposure when standard dosing regimens are used. Given the strong association between infliximab exposure and treatment response, an intensified dosing regimen, ideally supported by TDM and PK modeling, should be considered for hospitalized patients to improve treatment efficacy.
The full abstract can be found here.
Further content in inflammatory bowel disease.
Disclosure: This article was created by the touchIMMUNOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Support: No funding was received in the publication of this short article.
Cite: Increased infliximab clearance in hospitalized patients with severe ulcerative colitis may lead to underexposure. touchIMMUNOLOGY. February 26, 2025.
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