Interferon beta-1b

Compound Name:Interferon beta-1bMolecular Target:Type I interferon receptorsMolecular Structure:recombinant, humanLicensed Indication:relapsing forms of multiple sclerosisManufacturer and/or Distributor:Novartis; ; BayerInitial FDA Approval1993SummaryInterferon beta-lb (Betaseron, Extavia) is a protein product produced by E.coli containing the human interferon beta-1b gene with an induced mutation to substitute a serine residue for cysteine at position 17. It has a molecular weight of approximately 18,500 kDa, and it is not glycosylated. Interferon beta-1b binds to the Type I interferon receptor on a variety of cell types, and induces the upregulation of a large number of genes and has multiple physiological effects that are immunomodulatory, antiviral, or antiproliferative. Part of the therapeutic effect in multiple sclerosis (MS) might be attributable to some of these activities, i.e. up regulation of T suppressor cells, down regulation of inflammatory cytokine production and antigen presentation, and inhibition of lymphocyte trafficking to the central nervous system. In fact, however, the mechanism of action of interferon beta-1b in MS is not understood. Several of the genes that are upregulated by interferon beta-1b have been used as biomarkers during the development of the compound (neopterin, b2-microglobulin, MxA protein, and IL-10). Interferon beta-1b is administered at a dose of 0.25 mg by subcutaneous injections every other day. In 1993, interferon beta-1b was approved by the FDA for treatment of the relapsing/remitting form of MS. In 2006, the indication was added for new onset MS patients with MRI findings consistent with the diagnosis. Interferon beta-1b treatment reduces the frequency of clinical exacerbations. In 2009, the FDA approved the marketing of the same agent by Novartis, under the brand name Extavia. The U.S. Food approved BETACONECT, the only electronic autoinjector in the treatment of relapsing-remitting multiple sclerosis (RRMS) in September 2015 and this has been made available for Betaseron users. The clinical effects of Interferon beta-1b were studied in four randomized, multicenter, double-blind, placebo-controlled studies in patients with multiple sclerosis. In these studies, treatment with interferon-beta-1b was shown to reduce frequency of exacerbations, increase the proportion of exacerbation-free patients, reduce progression to disability and delay the time to development of a second exacerbation. A recent Cochrane review of interferons-beta against glatiramer acetate for relapsing-remitting multiple sclerosis showed comparable safety and efficacy. In controlled clinical trials, the most common adverse reactions (at least 5% more frequent on BETASERON than on placebo) were: injection site reaction, lymphopenia, flu-like symptoms, myalgia, leukopenia, neutropenia, increased liver enzymes, headache, hypertonia, pain, rash, insomnia, abdominal pain, and asthenia. It is advised to monitor CBC, liver function tests and signs and symptoms of hepatic injury in patients taking Betaseron. Betaseron is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, albumin, or mannitol.References

Betaseron: http://labeling.bayerhealthcare.com/html/products/pi/Betaseron_PI.pdf
Betaconnect: http://labeling.bayerhealthcare.com/html/products/Betaconnect_IFU.pdf
Extavia: http://www.pharma.us.novartis.com/product/pi/pdf/extavia.pdf



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6. Kappos L, Polman CH, Freedman MS, Edan G, Hartung HP, Miller DH, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology. 2006 Oct 10;67(7):1242-1249.
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8. Marziniak M, Meuth S. Current perspectives on interferon Beta-1b for the treatment of multiple sclerosis. Adv Ther. 2014 Sep;31(9):915-31. http://www.ncbi.nlm.nih.gov/pubmed/25182864

9. Freedman MS. Evidence for the efficacy of interferon beta-1b in delaying the onset of clinically definite multiple sclerosis in individuals with clinically isolated syndrome. Ther Adv Neurol Disord. 2014 Nov;7(6):279-88.
http://www.ncbi.nlm.nih.gov/pubmed/25371710

10.  Ziemssen T, Sylvester L, Rametta M, and Ross AP.  Patient Satisfaction with the New Interferon Beta-1b Autoinjector (BETACONNECT™). Neurol Ther. 2015 Dec;4(2):125-36. http://www.ncbi.nlm.nih.gov/pubmed/26662362

11. La Mantia L1, Di Pietrantonj C, Rovaris M, Rigon G, Frau S, Berardo F, Gandini A, Longobardi A, Weinstock-Guttman B, Vaona A.  Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2016 Nov 24;11:CD009333. https://www.ncbi.nlm.nih.gov/pubmed/27880972

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