Perianal fistulizing Crohn's disease increases infliximab clearance and causes low infliximab exposure (ATLANTIC)

Background and aims: In perianal fistulizing Crohn's disease (PFCD), higher infliximab (IFX) serum concentrations are associated with improved outcomes. PFCD patients frequently require dose intensification to reach recommended therapeutic targets. IFX pharmacokinetics (PK) in PFCD have not been previously characterized. We hypothesized that drug clearance (CL) is increased in PFCD compared to luminal Crohn's disease (LCD).

Methods

Patients with PFCD and LCD starting standard-dose intravenous IFX (5 mg/kg at weeks 0, 2, and 6, thereafter every 8 weeks) were enrolled. At every visit, serum samples were collected until week 52 to measure IFX trough levels (TL) and anti-drug antibodies. A population PK model was constructed using nonlinear mixed-effects modeling and adjusted for clinically relevant covariates.