title: The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis.
abstract: Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-beta-1b (IFN-beta 1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lesions on T2-weighted images. To examine the effect of IFN-beta 1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-beta has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.
authors.affiliation: Neuroimmunology Branch, National Institute for Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Stone
authors.forename: J A
authors.initials: JA
authors.lastname: Frank
authors.forename: P S
authors.initials: PS
authors.lastname: Albert
authors.forename: C
authors.initials: C
authors.lastname: Bash
authors.forename: M E
authors.initials: ME
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Maloni
authors.forename: H F
authors.initials: HF
authors.lastname: McFarland
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000187:drug effects*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D012008:Recurrence
chemical_list: D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a