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- Title
Exposure-Effect Population Model of Inolimomab, a Monoclonal Antibody Administered in First-Line Treatment for Acute Graft-Versus-Host Disease.
- Authors
Dartois, Céline; Freyer, Gilles; Michallet, Mauricette; Hénin, Emilie; You, Benoit; Darlavoix, Isabelle; Vermot-Desroches, Claudine; Tranchand, Brigitte; Girard, Pascal
- Abstract
Background and objective: Inolimomab, a monoclonal antibody against interleukin (IL)-2Ra (CD25) has shown promising results in the treatment of corticosteroid-resistant acute graft-versus-host disease (GvHD). The objective of the present study was to characterise the pharmacokinetic and pharmacodynamic properties of inolimomab as first-line treatment in this condition. Methods: The data came from 21 patients with acute GvHD (8 with an International Bone Marrow Transplant Registry [IBMTR] score of B, 11 with a score of C and 2 with a score of D) following haematopoietic stem cell transplantation after a median delay of 26 days (range 10–127 days). Inolimomab was administered at 0.1, 0.2, 0.3 or 0.4 mg/kg daily in association with methylprednisolone (2 mg/kg) for 8 or 16 days depending on the status at day 9. Then, for responder patients, administrations were continued three times weekly until day 28. Inolimomab concentrations and pharmacodynamic data (acute GvHD scores) were recorded during the study. The pharmacodynamic data were assessed in four grades according to the IBMTR and Glucksberg classification in parallel with Karnofsky scores. A population analysis was developed using a nonlinear mixed-effects model to define the pharmacokinetic model, to test covariates and, when apparent, to model the exposure-effect relationship by a proportional odds model. The modelling was finally qualified by a predictive check.
- Subjects
MONOCLONAL antibodies; IMMUNOGLOBULINS; BONE marrow cells; IMMUNE system; BONE marrow; THERAPEUTICS; PHARMACOKINETICS; PHARMACOLOGY
- Publication
Clinical Pharmacokinetics, 2007, Vol 46, Issue 5, p417
- ISSN
0312-5963
- Publication type
Article
- DOI
10.2165/00003088-200746050-00004