1. Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomised clinical trial
- Author
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Laurent Peyrin-Biroulet, Stéphane Paul, Anne Berger, Hubert Marotte, N Williet, Jean-Marc Phelip, Gilles Boschetti, Bernard Flourié, Xavier Roblin, Jean-Frederic Colombel, Stéphane Nancey, E. Del Tedesco, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU St Etienne, Laboratoire d'Immunologie, CHU Saint Etienne, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département Gastroentérologie New York, Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Azathioprine ,Gastroenterology ,Inflammatory bowel disease ,law.invention ,0302 clinical medicine ,Clinical Protocols ,Randomized controlled trial ,law ,Clinical endpoint ,heterocyclic compounds ,Pharmacology (medical) ,Prospective Studies ,Middle Aged ,3. Good health ,Antirheumatic Agents ,030220 oncology & carcinogenesis ,Combination ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Drug ,medicine.drug ,Adult ,medicine.medical_specialty ,Combination therapy ,Drug Administration Schedule ,Dose-Response Relationship ,Young Adult ,03 medical and health sciences ,Pharmacotherapy ,Drug Therapy ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,neoplasms ,Aged ,Dose-Response Relationship, Drug ,Hepatology ,business.industry ,Inflammatory Bowel Diseases ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Infliximab ,Surgery ,stomatognathic diseases ,business - Abstract
International audience; BACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. METHODS: Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5~mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25~mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. RESULTS: Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1~year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45~μg/mL, P=.9) and in group AZA down (3.95 vs 3.60~μg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15~μg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN \textless105~pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. CONCLUSIONS: Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.
- Published
- 2017
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