ArticleJournal of Crohn's & colitis2026
Perianal fistulizing Crohn's disease increases infliximab clearance and causes low infliximab exposure (ATLANTIC).
Article in Journal of Crohn's & colitis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
BACKGROUND AND
aimsIn 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).
methodsPatients 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.
resultsA total of 148 patients were included (62 PFCD, 86 LCD) with 756 serum samples analyzed. IFX PK was described by a two-compartment model with linear elimination. After adjusting for dose, weight, serum albumin, and anti-drug antibodies, population PK modeling revealed a 23% increase in IFX CL among patients with progressive perianal fistulas during the first 14 weeks (P = .007). During induction, recommended target IFX TL was achieved in fewer PFCD than LCD patients (43% vs 57%, P = .04). At week 14, PFCD patients had lower median IFX TL than LCD (2.9 vs 4.8 μg/mL, P = .02), with fewer PFCD patients reaching phenotype-specific target TL (9% vs 46%, P < .001) compared to LCD.
conclusionThe presence of perianal fistulas increases IFX CL in patients with Crohn's disease, resulting in significantly lower and frequently subtherapeutic serum concentrations after standard induction dosing.
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