![]() Magnetic resonance imaging outcomes also demonstrated treatment benefits. 0114) in the placebo, the every‐2‐weeks, and the every‐4‐weeks groups, respectively. 2 In the registration phase 3 ADVANCE study of 1512 relapsing MS patients, treatment with SC peginterferon beta‐1a 125 μg every 2 or 4 weeks, or treatment with placebo, resulted in significantly lower adjusted annualized relapse rates (ARRs primary endpoint) in both treatment arms vs placebo. Compared to unmodified intramuscular interferon beta‐1a 30 μg, peginterferon beta‐1a 125 μg SC yielded an approximately 11‐fold higher AUC and 2‐fold longer terminal half‐life. Both maximum serum concentration (C max) and area under the curve (AUC) were dose proportional, demonstrating linear pharmacokinetics (PK). 2 Following SC administration, peginterferon beta‐1a serum concentrations increased rapidly after dosing, reached peak levels after approximately 1 day, plateaued for approximately 3 to 4 days, and then gradually decreased to below the limit of quantification (BLQ) in 7 to 10 days, yielding a peginterferon beta‐1a dose‐independent terminal half‐life of approximately 2 days. 4 As shown in a phase 1 study, peginterferon beta‐1a had a longer half‐life and increased exposure as compared with interferon beta‐1a. 2, 3 Peginterferon beta‐1a was developed to reduce the dosing frequency of interferon beta‐1a by reducing clearance and prolonging half‐life to promote treatment adherence. ![]() ![]() ![]() However, because the pathogenesis of the disease is complex and multifaceted, the definite mechanism of action of peginterferon beta‐1a or interferon beta‐1a in MS is unknown. Peginterferon beta‐1a was formed by attaching a 20‐kDa methoxy poly(ethyleneglycol) (PEG) polymer to the α‐amino group of the N‐terminus of interferon (IFN) beta‐1a 1 and provides a less frequently injected subcutaneous (SC) therapy for relapsing multiple sclerosis (MS) with efficacy and safety characteristic of the IFN class.Ī definitive mechanism of action of peginterferon beta‐1a in MS is anticipated to be similar to interferon beta‐1a in MS, which binds to the type I IFN receptor on the surface of cells and elicits a cascade of intracellular events leading to the regulation of IFN‐responsive gene expression, and modulates immune responses that are believed to play a role in the pathogenesis of MS. ![]()
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