Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review

Abstract

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.

Efficiency of Orexin-A for Inflammatory Flare and Mucosal Healing in Experimental Colitis: Comparison with the Anti-TNF Alpha Infliximab

“…Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders affecting the gastrointestinal tract with the two main forms being ulcerative colitis (UC) and Crohn's disease. IBD etiology is not fully understood, but genetics and environment both play a significant role [1]. UC affects specifically the mucosal and submucosal layers of the colon and rectum.…”

“…The role of different cytokines, such as TNFα and other soluble mediators, in UC led to the development of anti-TNFα, anti-IL-12/23, anti-integrin α4β7 and Janus kinase inhibitors [5]. Infliximab (IFX) is a chimeric immunoglobulin G1 monoclonal antibody (mAb) that targets TNFα and which promotes mucosal healing and clinical remission [1]. IFX was the first mAb approved for the treatment of IBD and is widely used in the management of moderate-to-severe UC [6].…”