Working Paper Review Version 1 This version is not peer-reviewed

Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon-Beta-1a (Avonex)

Version 1 : Received: 9 January 2021 / Approved: 11 January 2021 / Online: 11 January 2021 (11:07:12 CET)

A peer-reviewed article of this Preprint also exists.

Cohan, S.L., Hendin, B.A., Reder, A.T. et al. Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex). CNS Drugs (2021). https://doi.org/10.1007/s40263-021-00822-z Cohan, S.L., Hendin, B.A., Reder, A.T. et al. Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex). CNS Drugs (2021). https://doi.org/10.1007/s40263-021-00822-z

Journal reference: CNS Drugs 2021
DOI: 10.1007/s40263-021-00822-z

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Keywords

multiple sclerosis; interferon; interferon beta-1a; COVID-19

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