engleski

A Novel Pegylated Interferon Beta-1a for Multiple Sclerosis: Safety, Pharmacology, and Biology

This study clinically evaluated a novel PEGylated form of interferon beta-1a (PEG-IFN beta-1a), a potential first-line treatment for relapsing multiple sclerosis, in healthy volunteers. Two randomized, blinded phase I studies were conducted: a single-dose study (n = 60) comparing subcutaneous or intramuscular PEG-IFN beta-1a (63, 125, or 188 μg)with intramuscular unmodified IFN beta-1a 30 μg and a multiple-dose study (n = 69) comparing subcutaneous PEG-IFN beta-1a dosed once every 2 or 4 weeks with placebo.Assessments included pharmacokinetic and pharmacodynamic (serum neopterin and 2′, 5′-OAS) measures, exploratory immune assessments, safety, and tolerability. A dose- proportional increase in PEG-IFN beta-1a exposure was observed, with a 4-fold greater exposure at 63 μg (6 million international units [MIU]) of PEG-IFN beta-1a than with 30 μg (6 MIU) intramuscular unmodified IFN beta-1a. Increases in neopterin and 2′, 5′-OAS levels and changes in T helper cell pathway gene expression and lymphocyte subsets were greater and more sustained with PEG-IFN beta-1a than with unmodified IFN beta-1a. PEG-IFN beta-1a was well tolerated, with only transient reductions in absolute neutrophils and some lymphocytes. Flu-like symptoms were a commonly reported adverse event. These data support the continued clinical development of PEG-IFN beta-1a as a potentially effective treatment for patients with relapsing multiple sclerosis.

multiple sclerosis ; pharmacokinetics and drug

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