Review: optimizing rescue therapy in acute severe ulcerative colitis using infliximab pharmacokinetics-a practical...

Corticosteroid-refractory acute severe ulcerative colitis (ASUC) remains a key management challenge despite an increasing understanding of rescue strategies. Due to the relative paucity of high-quality evidence, the use of infliximab in ASUC should be informed by pragmatic application of key clinical and pharmacological principles. This review synthesizes emerging evidence of infliximab pharmacology, describes key concepts of mechanisms of infliximab failure, and suggests an optimized approach to using infliximab in ASUC.

Relevant studies investigating infliximab in ASUC and infliximab pharmacology were identified by searching MEDLINE and EMBASE.

Infliximab pharmacokinetics are altered and undergo dynamic change during ASUC. Infliximab clearance is increased due to proteolytic degradation, target-mediated drug disposition, fecal losses and possibly early anti-drug antibody formation. Current pharmacokinetic models fail to account for both the time-varying nature of clearance and the reciprocal relationship between pharmacokinetics and pharmacodynamics. The propensity to respond to infliximab depends on both pharmacokinetic and pharmacodynamic factors. Patients with high clearance are at risk of pharmacokinetic failure and may benefit from escalated induction. Pre-treatment determination of clearance can be estimated by considering factors including higher weight, male sex, lower albumin, higher inflammatory markers, and more severe endoscopic disease. On-treatment clearance calculation based on peak concentrations may be feasible to inform dose escalation. Early response assessment and careful use of sequential therapy may benefit patients experiencing infliximab pharmacodynamic failure.

The use of infliximab in corticosteroid-refractory ASUC may be optimized by pre-treatment risk assessment, dose escalation, on-treatment response assessment, and consideration of sequential therapy.