title: A Population Approach to Characterize Interferon Beta-1b Effect on Contrast Enhancing Lesions in Patients With Relapsing Remitting Multiple Sclerosis.
abstract: In patients with relapsing-remitting multiple sclerosis (RRMS), interferon beta-1b (IFNβ-1b) reduces the occurrence of contrast enhancing lesions (CELs) on magnetic resonance imaging (MRI). Questions remain on the stability of IFNβ-1b effect over time and its action beyond the reduction of CELs. In this study, we described the IFNβ-1b effect by a mixed effects model, quantifying the interpatient variability associated with its parameters. Using a negative binomial distribution model as a natural history model, the effect of IFNβ-1b was evaluated using different mathematical functions of time. IFNβ-1b produced a decrease in the expected CEL numbers, inhibiting the formation of new CELs but did not promote the resolution of the already-formed ones. Based on the final selected model, simulations were carried out to optimize the combined IFNβ-1b-corticosteroid therapy as a proof-of-concept. In summary, we provide evidence on the dynamics of CELs under IFNβ-1b treatment that can be used to monitor the effects of therapies in MS.
authors.affiliation: Indiana University School of Medicine Indianapolis, Indiana, USA ; Indiana Clinical and Translational Sciences Institute (CTSI) Indianapolis, Indiana, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gulati
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, Maryland, USA.
authors.forename: F
authors.initials: F
authors.lastname: Bagnato
authors.affiliation: Center for Neuroimmunology, Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Hospital Clinic of Barcelona Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Villoslada
authors.affiliation: Indiana University School of Medicine Indianapolis, Indiana, USA ; Indiana Clinical and Translational Sciences Institute (CTSI) Indianapolis, Indiana, USA.
authors.forename: N
authors.initials: N
authors.lastname: Velez de Mendizabal