4.6 Article

Accelerated Clearance of Infliximab is Associated With Treatment Failure in Patients With Corticosteroid-Refractory Acute Ulcerative Colitis

Journal

JOURNAL OF CROHNS & COLITIS
Volume 12, Issue 6, Pages 662-669

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/ecco-jcc/jjy028

Keywords

Infliximab; ulcerative colitis; pharmacokinetics

Funding

  1. CIHR / Canadian Association of Gastroenterology [CAG] / Abbvie IBD Fellowship
  2. Gale and Graham Wright Chair in Digestive Diseases at Mount Sinai Hospital, Toronto

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Background and Aims: A significant proportion of patients with corticosteroid-refractory acute ulcerative colitis [UC] fail therapy. We aimed to assess the pharmacokinetics [PK] of infliximab [IFX] in patients with corticosteroid-refractory acute UC and determine the association between induction IFX PK and short-and long-term therapy outcome. Methods: A population PK model was developed using data from 51 patients with UC [n = 42] and Crohn's disease [n = 9]. A subset of patients [n = 36] with acute corticosteroid-refractory UC (median Mayo score 11 [range 8-12]; 33 of 36 hospitalized; median corticosteroid dose at study entry 50mg prednisolone equivalent IV/oral) commencing IFX were studied to assess further correlations between PK from the first induction dose and therapy outcomes. Serial induction drug levels from the 36 UC patients were collected, facilitating population-based PK analysis. IFX and antibodies-to-infliximab [ATIs] concentrations were determined using Ansr (TM) IFX assay [Prometheus Inc.]. Results: The Week 14 clinical response and Week 54 corticosteroid-free remission rates were 78% [28/36] and 53% [19/36], respectively. The estimated effective IFX half-life [T 1/2] (median [range]) and clearance (median [range]) were 8.42 [3.94-22.03] days and 0.50 [0.19-1.41] L/day respectively. Longer induction IFX T 1/2 and lower clearance were associated with the Week 14 clinical response [p = 0.005] and the Week 54 corticosteroid-free remission rates [p = 0.007]. Conclusions: Accelerated IFX clearance occurs in corticosteroid-refractory acute UC and is associated with therapy failure. These data support the use of accelerated IFX induction regimens in patients with corticosteroid-refractory acute UC failing conventional dosing regimens.

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