View source for Interferon beta-1a

{{short description|Cytokine in the interferon family}}
{{drugbox
| Verifiedfields = changed
| verifiedrevid = 458271076
| image = 1AU1 Human Interferon-Beta01.png
| width = 250
| alt = 

<!-- Clinical data -->
| tradename = Avonex, Rebif, Plegridy, others
| Drugs.com = {{drugs.com|ppa|interferon-beta-1a}}
| MedlinePlus = a604005
| licence_EU = yes
| DailyMedID = Interferon_beta-1a
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU = D
| pregnancy_AU_comment = 
| pregnancy_category= 
| routes_of_administration = [[Subcutaneous injection|Subcutaneous]], [[Intramuscular injection|intramuscular]]
| ATC_prefix = L03
| ATC_suffix = AB07

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment  = 
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment  = 
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment  = 
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment  = 
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  = 
| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  = 
| legal_US = Rx-only
| legal_US_comment  = <ref name="Avonex FDA label" /><ref name="Rebif FDA label" />
| legal_EU          = Rx-only
| legal_EU_comment  = <ref>{{cite web | title=Avonex EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/avonex | access-date=1 October 2020 | archive-date=26 October 2020 | archive-url=https://web.archive.org/web/20201026073314/https://www.ema.europa.eu/en/medicines/human/EPAR/avonex | url-status=live }}</ref><ref>{{cite web | title=Rebif EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/rebif | access-date=1 October 2020 | archive-date=11 November 2020 | archive-url=https://web.archive.org/web/20201111210214/https://www.ema.europa.eu/en/medicines/human/EPAR/rebif | url-status=live }}</ref>
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  = 
| legal_status      = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability   = 
| protein_bound     = 
| metabolism        = 
| metabolites       = 
| onset             = 
| elimination_half-life = 10 hrs
| duration_of_action = 
| excretion         = 

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 145258-61-3
| CAS_supplemental  = 
| PubChem           = 
| IUPHAR_ligand = 8339 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00060
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = XRO4566Q4R
| KEGG_Ref          = 
| KEGG = D04554
| ChEBI_Ref         = 
| ChEBI             = 
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201562
| NIAID_ChemDB      = 
| PDB_ligand        = 
| synonyms          = 

<!-- Chemical data -->
| IUPAC_name = Human interferon beta
| C=908 | H=1408 | N=246 | O=252 | S=7
}}

'''Interferon beta-1a''' (also '''interferon beta 1-alpha''') is a [[cytokine]] in the [[interferon]] family used to treat [[multiple sclerosis]] (MS).<ref name="pmid16207073">{{cite journal | vauthors = Murdoch D, Lyseng-Williamson KA | title = Spotlight on subcutaneous recombinant interferon-beta-1a (Rebif) in relapsing-remitting multiple sclerosis | journal = BioDrugs | volume = 19 | issue = 5 | pages = 323–325 | year = 2005 | pmid = 16207073 | doi = 10.2165/00063030-200519050-00005 | s2cid = 3122427 }}</ref> It is produced by mammalian cells, while [[interferon beta-1b]] is produced in modified ''[[E. coli]]''.<ref>{{cite journal | vauthors = Giovannoni G, Munschauer FE, Deisenhammer F | title = Neutralising antibodies to interferon beta during the treatment of multiple sclerosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 73 | issue = 5 | pages = 465–469 | date = November 2002 | pmid = 12397132 | pmc = 1738139 | doi = 10.1136/jnnp.73.5.465 }}</ref>  Some research indicates that interferon injections  may result in an 18–38% reduction in the rate of MS relapses.<ref name="About.com">{{cite web|url = http://ms.about.com/od/treatments/a/AVONEX.htm|title = Is Avonex Right for You?|access-date = 2008-05-07| vauthors = Stachowiak J |year = 2008|archive-date = 2016-03-03|archive-url = https://web.archive.org/web/20160303175612/http://ms.about.com/od/treatments/a/AVONEX.htm}}</ref>

Interferon beta has not been shown to slow the advance of disability.<ref name="ncbi.nlm.nih.gov">{{cite journal | vauthors = Shirani A, Zhao Y, Karim ME, Evans C, Kingwell E, van der Kop ML, Oger J, Gustafson P, Petkau J, Tremlett H | display-authors = 6 | title = Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis | journal = JAMA | volume = 308 | issue = 3 | pages = 247–256 | date = July 2012 | pmid = 22797642 | doi = 10.1001/jama.2012.7625 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Kappos L, Kuhle J, Multanen J, Kremenchutzky M, Verdun di Cantogno E, Cornelisse P, Lehr L, Casset-Semanaz F, Issard D, Uitdehaag BM | display-authors = 6 | title = Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15 | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 86 | issue = 11 | pages = 1202–1207 | date = November 2015 | pmid = 26374702 | pmc = 4680156 | doi = 10.1136/jnnp-2014-310024 }}</ref><ref>{{cite journal | vauthors = Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, Liu S, Zhu Y, Seddighzadeh A, Hung S, Deykin A | display-authors = 6 | title = Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study | journal = The Lancet. Neurology | volume = 13 | issue = 7 | pages = 657–665 | date = July 2014 | pmid = 24794721 | doi = 10.1016/S1474-4422(14)70068-7 | s2cid = 45183415 }}</ref><ref>{{cite journal | vauthors = Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE, Priore RL, Pullicino PM, Scherokman BJ, Whitham RH | display-authors = 6 | title = Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG) | journal = Annals of Neurology | volume = 39 | issue = 3 | pages = 285–294 | date = March 1996 | pmid = 8602746 | doi = 10.1002/ana.410390304 | s2cid = 24663294 }}</ref> Interferons are not a cure for MS (there is no known cure); the claim is that interferons may slow the progress of the disease if started early and continued for the duration of the disease.<ref name="pmid21205679"/>

{{TOC limit|3}}

==Medical uses==

=== Clinically isolated syndrome ===
The earliest clinical presentation of relapsing-remitting multiple sclerosis is the clinically isolated syndrome (CIS), that is, a single attack of a single symptom. During a CIS, there is a subacute attack suggestive of [[demyelination]] which should be included in the spectrum of MS phenotypes.<ref>{{cite journal | vauthors = Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, Wolinsky JS, Balcer LJ, Banwell B, Barkhof F, Bebo B, Calabresi PA, Clanet M, Comi G, Fox RJ, Freedman MS, Goodman AD, Inglese M, Kappos L, Kieseier BC, Lincoln JA, Lubetzki C, Miller AE, Montalban X, O'Connor PW, Petkau J, Pozzilli C, Rudick RA, Sormani MP, Stüve O, Waubant E, Polman CH | display-authors = 6 | title = Defining the clinical course of multiple sclerosis: the 2013 revisions | journal = Neurology | volume = 83 | issue = 3 | pages = 278–286 | date = July 2014 | pmid = 24871874 | pmc = 4117366 | doi = 10.1212/WNL.0000000000000560 }}</ref> Treatment with [[interferon]]s after an initial attack decreases the risk of developing clinical definite MS.<ref name="pmid18970977"/><ref name="pmid21205678">{{cite journal | vauthors = Bates D | title = Treatment effects of immunomodulatory therapies at different stages of multiple sclerosis in short-term trials | journal = Neurology | volume = 76 | issue = 1 Suppl 1 | pages = S14–S25 | date = January 2011 | pmid = 21205678 | doi = 10.1212/WNL.0b013e3182050388 | s2cid = 362182 }}</ref>

=== Relapsing-remitting MS ===
Medications are modestly effective at decreasing the number of attacks in relapsing-remitting multiple sclerosis<ref>{{cite journal | vauthors = Rice GP, Incorvaia B, Munari L, Ebers G, Polman C, D'Amico R, Filippini G | title = Interferon in relapsing-remitting multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2001 | issue = 4 | article-number = CD002002 | date = 2001 | pmid = 11687131 | pmc = 7017973 | doi = 10.1002/14651858.CD002002 }}</ref> and in reducing the accumulation of brain lesions, which is measured using [[gadolinium]]-[[MRI contrast agent|enhanced]] [[magnetic resonance imaging]] (MRI).<ref name="pmid18970977"/> Interferons reduce relapses by approximately 30% and their safe profile make them the first-line treatments.<ref name="pmid18970977"/> Nevertheless, not all the patients are responsive to these therapies. It is known that 30% of MS patients are non-responsive to Beta interferon.<ref name="pmid18690496">{{cite journal | vauthors = Bertolotto A, Gilli F | title = Interferon-beta responders and non-responders. A biological approach | journal = Neurological Sciences | volume = 29 | issue = Suppl 2 | pages = S216–S217 | date = September 2008 | pmid = 18690496 | doi = 10.1007/s10072-008-0941-2 | s2cid = 19618597 }}</ref> They can be classified in genetic, pharmacological and pathogenetic non-responders.<ref name="pmid18690496"/> One of the factors related to non-respondance is the presence of high levels of interferon beta neutralizing  [[antibodies]]. Interferon therapy, and specially interferon beta 1b, induces the production of  neutralizing  antibodies, usually in the second 6 months of treatment, in 5 to 30% of treated patients.<ref name="pmid18970977"/> Moreover, a subset of RRMS patients with specially active MS, sometimes called "rapidly worsening MS" are normally non-responders to interferon beta 1a.<ref>{{cite journal | vauthors = Buttinelli C, Clemenzi A, Borriello G, Denaro F, Pozzilli C, Fieschi C | title = Mitoxantrone treatment in multiple sclerosis: a 5-year clinical and MRI follow-up | journal = European Journal of Neurology | volume = 14 | issue = 11 | pages = 1281–1287 | date = November 2007 | pmid = 17956449 | doi = 10.1111/j.1468-1331.2007.01969.x | s2cid = 36392563 }}</ref><ref>{{cite journal | vauthors = Boster A, Edan G, Frohman E, Javed A, Stuve O, Tselis A, Weiner H, Weinstock-Guttman B, Khan O | display-authors = 6 | title = Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician | journal = The Lancet. Neurology | volume = 7 | issue = 2 | pages = 173–183 | date = February 2008 | pmid = 18207115 | doi = 10.1016/S1474-4422(08)70020-6 | s2cid = 40367120 }}</ref>

While more studies of the long-term effects of the drugs are needed,<ref name="pmid21205679"/><ref name="pmid18970977"/>  existing data on the effects of interferons indicate that early-initiated long-term therapy is safe and it is related to better outcomes.<ref name="pmid21205679">{{cite journal | vauthors = Freedman MS | title = Long-term follow-up of clinical trials of multiple sclerosis therapies | journal = Neurology | volume = 76 | issue = 1 Suppl 1 | pages = S26–S34 | date = January 2011 | pmid = 21205679 | doi = 10.1212/WNL.0b013e318205051d | s2cid = 16929304 }}</ref>

==Side effects==
[[File:Implant.png|right|thumb|Injectable medications can produce irritation or bruises at injection site. The bruise depicted was produced by a subcutaneous injection.]]

Interferon beta-1a is available only in injectable forms, and can cause skin reactions at the injection site that may include cutaneous [[necrosis]]. Skin reactions with interferon beta are more common with subcutaneous administration and vary greatly in their clinical presentation.<ref name=pmid10563602/> They usually appear within the first month of treatment albeit their frequence and importance diminish after six months of treatment.<ref name=pmid10563602/> Skin reactions are more prevalent in women.<ref name=pmid10563602/> Mild skin reactions usually do not impede treatment whereas necroses appear in around 5% of patients and lead to the discontinuation of the therapy.<ref name=pmid10563602/> Also over time, a visible dent at the injection site due to the local destruction of fat tissue, known as [[lipoatrophy]], may develop, however, this rarely occurs with interferon treatment.<ref>{{cite journal | vauthors = Edgar CM, Brunet DG, Fenton P, McBride EV, Green P | title = Lipoatrophy in patients with multiple sclerosis on glatiramer acetate | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 31 | issue = 1 | pages = 58–63 | date = February 2004 | pmid = 15038472 | doi = 10.1017/s0317167100002845 | doi-access = free }}</ref>

[[Interferon]]s, a subclass of [[cytokines]], are produced in the body during illnesses such as [[influenza]] in order to help fight the infection. They are responsible for many of the symptoms of influenza infections, including [[fever]], [[myalgia|muscle aches]], [[fatigue (medical)|fatigue]], and [[headache]]s.<ref name="pmid16253889">{{cite journal | vauthors = Eccles R | title = Understanding the symptoms of the common cold and influenza | journal = The Lancet. Infectious Diseases | volume = 5 | issue = 11 | pages = 718–725 | date = November 2005 | pmid = 16253889 | pmc = 7185637 | doi = 10.1016/S1473-3099(05)70270-X }}</ref> Many patients report influenza-like symptoms hours after taking interferon beta that usually improve within 24 hours, being such symptoms related to the temporary increase of cytokines.<ref name="pmid18970977">{{cite journal | vauthors = Compston A, Coles A | title = Multiple sclerosis | journal = Lancet | volume = 372 | issue = 9648 | pages = 1502–1517 | date = October 2008 | pmid = 18970977 | doi = 10.1016/S0140-6736(08)61620-7 | s2cid = 195686659 }}</ref><ref name=pmid10563602>{{cite journal | vauthors = Walther EU, Hohlfeld R | title = Multiple sclerosis: side effects of interferon beta therapy and their management | journal = Neurology | volume = 53 | issue = 8 | pages = 1622–1627 | date = November 1999 | pmid = 10563602 | doi = 10.1212/wnl.53.8.1622 | s2cid = 30330292 }}</ref> This reaction tends to disappear after 3 months of treatment and its symptoms can be treated with over-the-counter [[nonsteroidal anti-inflammatory drug]]s, such as [[ibuprofen]], that reduce fever and pain.<ref name=pmid10563602/> Another common transient secondary effect with interferon-beta is a functional deterioration of already existing symptoms of the disease.<ref name=pmid10563602/> Such deterioration is similar to the one produced in MS patients due to heat, fever or stress ([[Uhthoff's phenomenon]]), usually appears within 24 hours of treatment, is more common in the initial months of treatment, and may last several days.<ref name=pmid10563602/> A symptom specially sensitive to worsening is [[spasticity]].<ref name=pmid10563602/> Interferon-beta can also reduce numbers of [[white blood cell]]s ([[leukopenia]]), [[lymphocyte]]s ([[lymphopenia]]) and [[neutrophil]]s ([[neutropenia]]), as well as affect [[liver]] function.<ref name=pmid10563602/> In most cases these effects are non-dangerous and reversible after cessation or reduction of treatment.<ref name=pmid10563602/> Nevertheless, recommendation is that all patients should be monitored through laboratory [[Blood test|blood analyses]], including [[liver function tests]], to ensure safe use of interferons.<ref name=pmid10563602/>

To help prevent injection-site reactions, patients are advised to rotate injection sites and use an aseptic injection technique. Injection devices are available to optimize the injection process.  Side effects are often onerous enough that many patients ultimately discontinue taking interferons {{citation needed|date=March 2013}} (or [[glatiramer acetate]], a comparable disease-modifying therapy requiring regular injections).

==Mechanism of action==
Interferon beta balances the expression of pro- and anti-inflammatory agents in the brain, and reduces the number of inflammatory cells that cross the [[blood brain barrier]].<ref name="pmid21649449">{{cite journal | vauthors = Kieseier BC | title = The mechanism of action of interferon-β in relapsing multiple sclerosis | journal = CNS Drugs | volume = 25 | issue = 6 | pages = 491–502 | date = June 2011 | pmid = 21649449 | doi = 10.2165/11591110-000000000-00000 | s2cid = 25516515 }}</ref> Overall, therapy with interferon beta leads to a reduction of neuron inflammation.<ref name="pmid21649449"/> Moreover, it is also thought to increase the production of [[nerve growth factor]] and consequently improve neuronal survival.<ref name="pmid21649449"/> In vitro, interferon beta reduces production of [[T helper 17 cell|Th17 cells]] which are a subset of T lymphocytes believed to have a role in the pathophysiology of MS.<ref>{{cite journal | vauthors = Mitsdoerffer M, Kuchroo V | title = New pieces in the puzzle: how does interferon-beta really work in multiple sclerosis? | journal = Annals of Neurology | volume = 65 | issue = 5 | pages = 487–488 | date = May 2009 | pmid = 19479722 | doi = 10.1002/ana.21722 | s2cid = 42050086 }}</ref>

[[File:Signal transduction pathways.svg|alt=A scalable vector graphic of signal transduction pathways|thumb|Cytokines, such as '''interferons''', typically activate second messenger systems, like JAK-STAT pathways, as illustrated on the left side of the diagram. Conversely, '''hormones''' typically activate different signaling pathways, like G protein-coupled receptors, seen at the top of the figure.]]

== Society and culture ==

===Brand names===

====Avonex====
Avonex was approved in the US in 1996,<ref name="Approval of Avonex">{{cite news | title=F.D.A. Approves a Biogen Drug for Treating Multiple Sclerosis | website=[[The New York Times]] | date=8 May 1996 | url=https://www.nytimes.com/1996/05/18/business/fda-approves-a-biogen-drug-for-treating-multiple-sclerosis.html | access-date=16 January 2021 | archive-date=22 January 2021 | archive-url=https://web.archive.org/web/20210122104645/https://www.nytimes.com/1996/05/18/business/fda-approves-a-biogen-drug-for-treating-multiple-sclerosis.html | url-status=live }}</ref> and in the European Union in 1997, and is registered in more than 80 countries worldwide.{{cn|date=October 2020}} It is the leading MS therapy in the US, with around 40% of the overall market, and in the European Union, with around 30% of the overall market.{{citation needed|date=April 2015}} It is produced by the [[Biogen]] [[biotechnology]] company, originally under competition protection in the US under the [[Orphan Drug Act]].

Avonex is sold in three formulations, a lyophilized powder requiring reconstitution, a pre-mixed liquid syringe kit, and a pen; it is administered via [[intramuscular injection]].<ref name="Avonex FDA label">{{cite web | title=Avonex- interferon beta-1a kit Avonex Pen- interferon beta-1a injection, solution Avonex- interferon beta-1a injection, solution | website=DailyMed | date=30 March 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d70a39cc-de15-4c12-a1ec-8063b69ea0e1 | access-date=1 October 2020 | archive-date=25 March 2021 | archive-url=https://web.archive.org/web/20210325060926/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d70a39cc-de15-4c12-a1ec-8063b69ea0e1 | url-status=live }}</ref>

====Rebif====
Rebif is a disease-modifying drug (DMD) used to treat multiple sclerosis in cases of clinically isolated syndromes as well as relapsing forms of multiple sclerosis and is similar to the interferon beta protein produced by the human body. It is co-marketed by [[Merck Serono]] and [[Pfizer]] in the US under an exception to the [[Orphan Drug Act]]. {{cn|date=October 2020}} It was approved in the European Union in 1998, and in the US in 2002; it has since been approved in more than 90 countries worldwide including Canada and Australia.{{cn|date=October 2020}} EMD Serono has had sole rights to Rebif in the US since January 2016.<ref>{{Cite web|url=https://www.emdgroup.com/en/expertise/neurology-and-immunology.html|title=Neurology & Immunology|website=EMD Group|access-date=2021-08-08|archive-date=2024-04-07|archive-url=https://web.archive.org/web/20240407080938/https://www.emdgroup.com/en/expertise/neurology-and-immunology.html|url-status=live}}</ref><ref>{{Cite press release|url=https://www.prnewswire.com/news-releases/emd-serono-takes-on-exclusive-promotion-of-rebif-interferon-beta-1a-in-the-us-300205988.html|title=EMD Serono Takes on Exclusive Promotion of Rebif (interferon beta-1a) in the US|publisher=EMD Serono|via=PR Newswire|access-date=2021-08-08|archive-date=2023-03-29|archive-url=https://web.archive.org/web/20230329045259/https://www.prnewswire.com/news-releases/emd-serono-takes-on-exclusive-promotion-of-rebif-interferon-beta-1a-in-the-us-300205988.html|url-status=live}}</ref> Rebif is administered via [[subcutaneous injection]].<ref name="Rebif FDA label">{{cite web | title=Rebif- interferon beta-1a kit Rebif Rebidose- interferon beta-1a kit Rebif- interferon beta-1a injection, solution Rebif- interferon beta-1a injection, solution Rebif Rebidose- interferon beta-1a injection, solution | website=DailyMed | date=5 June 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6fcb5d2-8fcd-44fa-a838-b84ee5f44f0f | access-date=1 October 2020 | archive-date=24 March 2021 | archive-url=https://web.archive.org/web/20210324222529/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6fcb5d2-8fcd-44fa-a838-b84ee5f44f0f | url-status=live }}</ref>

====Cinnovex====
Cinnovex is the brand name of recombinant Interferon beta-1a, which is manufactured as biosimilar/biogeneric in [[Iran]].  It is produced in a lyophilized form and sold with [[distilled water]] for injection. Cinnovex was developed at the [[Fraunhofer Society]] in collaboration with [[CinnaGen]], and is the first therapeutic protein from a [[Fraunhofer Society|Fraunhofer laboratory]] to be approved as biogeneric / biosimilar medicine. There are several clinical studies to prove the similarity of CinnoVex and Avonex.<ref>{{cite journal | vauthors = Nafissi S, Azimi A, Amini-Harandi A, Salami S, shahkarami MA, Heshmat R | title = Comparing efficacy and side effects of a weekly intramuscular biogeneric/biosimilar interferon beta-1a with Avonex in relapsing remitting multiple sclerosis: a double blind randomized clinical trial | journal = Clinical Neurology and Neurosurgery | volume = 114 | issue = 7 | pages = 986–989 | date = September 2012 | pmid = 22429566 | doi = 10.1016/j.clineuro.2012.02.039 | s2cid = 9236986 }}</ref> A more water-soluble variant is currently being investigated by the Vakzine Projekt Management (VPM) GmbH in Braunschweig, Germany.

====Plegridy====
{{Main|Peginterferon beta-1a}}
{{See also|Multiple_sclerosis_research#Phase_III}}
Plegridy is a brand name of a [[pegylated]] form of Interferon beta-1a. Plegridy's advantage is it only needs injecting once every two weeks.<ref name="Plegridy FDA label">{{cite web | title=Plegridy- peginterferon beta-1a kit Plegridy Pen- peginterferon beta-1a kit Plegridy- peginterferon beta-1a injection, solution | website=DailyMed | date=19 July 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08f0ea03-4e6d-195d-aef4-886e32befa95 | access-date=30 March 2020 | archive-date=26 June 2020 | archive-url=https://web.archive.org/web/20200626040916/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08f0ea03-4e6d-195d-aef4-886e32befa95 | url-status=live }}</ref>

====Betaferon (interferon beta-1b)====
Closely related to interferon beta-1a is [[interferon beta-1b]], which is also indicated for MS, but is formulated with a different dose and administered with a different frequency. Each drug has a different safety/efficacy profile.<ref>{{cite journal | vauthors = Nikfar S, Rahimi R, Abdollahi M | title = A meta-analysis of the efficacy and tolerability of interferon-β in multiple sclerosis, overall and by drug and disease type | journal = Clinical Therapeutics | volume = 32 | issue = 11 | pages = 1871–1888 | date = October 2010 | pmid = 21095482 | doi = 10.1016/j.clinthera.2010.10.006 }}</ref> Interferon beta-1b is marketed only by [[Bayer]] in the US as Betaseron, and outside the US as Betaferon.

===Economics===
In the United States, {{as of|2015|lc=yes}}, the cost is between US$1,284 and US$1,386 per 30 mcg vial.<ref>{{cite news|vauthors=Langreth R|title=Decoding Big Pharma's Secret Drug Pricing Practices|url=https://www.bloomberg.com/graphics/2016-drug-prices/|access-date=15 July 2016|publisher=Bloomberg|date=June 29, 2016|archive-date=13 July 2016|archive-url=https://web.archive.org/web/20160713133019/http://www.bloomberg.com/graphics/2016-drug-prices/|url-status=live}}</ref> As of 2020, the National Average Drug Acquisition Cost (NADAC) in the United States for Avonex was $6,872.94 for a 30 mcg kit.<ref>{{Cite web|url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2020-02-12/2ghv-q5xv|title=NADAC as of 2020-02-12 | work = Centers for Medicare and Medicaid Services|language=en|access-date=2020-02-18|archive-date=2020-02-18|archive-url=https://web.archive.org/web/20200218171241/https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2020-02-12/2ghv-q5xv}}</ref>

Avonex and Rebif are on the top ten best-selling multiple sclerosis drugs of 2013.<ref>{{Cite web|url=https://www.fiercepharma.com/special-report/top-10-best-selling-multiple-sclerosis-drugs-of-2013|title=The top 10 best-selling multiple sclerosis drugs of 2013|website=FiercePharma|date=9 September 2014|access-date=8 August 2021|archive-date=26 February 2024|archive-url=https://web.archive.org/web/20240226115050/https://www.fiercepharma.com/special-report/top-10-best-selling-multiple-sclerosis-drugs-of-2013|url-status=live}}</ref>

It is an example of a [[specialty drugs|specialty drug]] that would only be available through a [[specialty pharmacy]]. This is because it requires a refrigerated chain of distribution and costs $17,000 a year.<ref name="ncbi_2013">{{cite journal | vauthors = Gleason PP, Alexander GC, Starner CI, Ritter ST, Van Houten HK, Gunderson BW, Shah ND | title = Health plan utilization and costs of specialty drugs within 4 chronic conditions | journal = Journal of Managed Care Pharmacy | volume = 19 | issue = 7 | pages = 542–548 | date = September 2013 | pmid = 23964615 | doi = 10.18553/jmcp.2013.19.7.542 | pmc = 10437312 }}</ref>

{| class="wikitable"
|-
! No. !! 2013 Global Sales !! [[International Nonproprietary Name|INN]] !! Brand names !! Companies
|-
| 1 || $4.33 billion || [[Glatiramer acetate]] || Copaxone || Teva
|-
| 2 || $3.00 billion || Interferon beta 1a || Avonex || Biogen Idec
|-
| 3 || $2.51 billion || Interferon beta 1a || Rebif || Merck KGaA
|-
| 4 || $1.93 billion || [[Fingolimod]] || Gilenya || Novartis
|-
| 5 || $1.41 billion || [[Natalizumab]] || Tysabri || Biogen Idec
|-
| 6 || $1.38 billion || [[Interferon beta 1b]] || Betaseron/Betaferon || Bayer HealthCare
|-
| 7 || $876 million || [[Dimethyl fumarate]] || Tecfidera || Biogen Idec
|-
| 8 || $303 million || [[4-Aminopyridine]] || Ampyra || [[Acorda Therapeutics]]
|-
| 9 || $250 million || [[Adrenocorticotropic hormone]] || H.P. Acthar Gel || Questcor Pharmaceuticals
|-
| 10 || $221 million || [[Teriflunomide]] || Aubagio || Sanofi
|}

== Research ==
=== COVID-19 ===
{{See also|Coronavirus disease 2019#Research|COVID-19 drug repurposing research}}

Interferon beta-1a administered subcutaneously or intravenously was investigated since March 2020 as a potential treatment in patients hospitalized with [[COVID-19]] in a multinational [[Solidarity trial]] (initially in combination with [[lopinavir]]) but it did not reduce in-hospital mortality compared to local standard of care.<ref name="pmid33264556">{{cite journal | vauthors = Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernández García C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HB, Cerrato N, Chow TS, Como N, Eustace J, García PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portolés A, Rasmin MR, Raza A, Rees H, Reges PP, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JA, Stevanovikj M, Tacconelli E, Tikkinen KA, Trelle S, Zaid H, Røttingen JA, Swaminathan S | display-authors = 6 | title = Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results | journal = The New England Journal of Medicine | volume = 384 | issue = 6 | pages = 497–511 | date = February 2021 | pmid = 33264556 | pmc = 7727327 | doi = 10.1056/NEJMoa2023184 }}</ref> 

SNG001, an inhalation formulation of interferon beta-1a, is being developed as a treatment for COVID-19 by [[Synairgen]].<ref>{{Cite web|url=https://www.covidtrialathome.com/|title=COVID Trial at Home - developed by Synairgen|website=Covid Trial at Home - developed by Synairgen|access-date=2021-08-08|archive-date=2022-05-07|archive-url=https://web.archive.org/web/20220507151458/https://www.covidtrialathome.com/}}</ref><ref>{{Cite web|url=https://medicalxpress.com/news/2020-05-university-led-covid19-drug-trial-home.html|title=University-led COVID19 drug trial expands into home testing|website=medicalxpress|access-date=2020-05-27|archive-date=2020-06-06|archive-url=https://web.archive.org/web/20200606011637/https://medicalxpress.com/news/2020-05-university-led-covid19-drug-trial-home.html|url-status=live}}</ref> A pilot trial in hospitalized patients showed higher odds of clinical improvement with SNG001 compared to placebo<ref name="pmid33189161">{{cite journal | vauthors = Monk PD, Marsden RJ, Tear VJ, Brookes J, Batten TN, Mankowski M, Gabbay FJ, Davies DE, Holgate ST, Ho LP, Clark T, Djukanovic R, Wilkinson TM | display-authors = 6 | title = Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial | journal = The Lancet. Respiratory Medicine | volume = 9 | issue = 2 | pages = 196–206 | date = February 2021 | pmid = 33189161 | pmc = 7836724 | doi = 10.1016/S2213-2600(20)30511-7 }}</ref> and in January 2021 a phase 3 trial in this population started.<ref>{{cite web | title=Synairgen begins large-scale trial of inhaled COVID-19 treatment | website=PharmaTimes | date=13 January 2021 | url=https://www.pharmatimes.com/news/synairgen_begins_large-scale_trial_of_inhaled_covid-19_treatment_1361172 | access-date=7 August 2021 | archive-date=7 August 2021 | archive-url=https://web.archive.org/web/20210807001259/https://www.pharmatimes.com/news/synairgen_begins_large-scale_trial_of_inhaled_covid-19_treatment_1361172 | url-status=live }}</ref>

== References ==
{{Reflist }}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/interferon%20beta%201a | archive-url = https://web.archive.org/web/20200721025644/https://druginfo.nlm.nih.gov/drugportal/name/interferon%20beta%201a | archive-date = July 21, 2020 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Interferon beta-1a }}
* {{cite web | title=Interferon Beta-1a Intramuscular Injection | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a693040.html }}

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