Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab

摘要

BackgroundInfliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. ObjectiveThis study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. MethodsData were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5?mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72?h and at 5, 7, 14, 21, 28, 42, 56, and 70?days after administration. ADAs were measured pre-dose and at 29 and 71?days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. ResultsAt 10?weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89?±?2.69 vs. 9.90?±?1.74?ml/h; p 2?=?0.5494; p ConclusionADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.