View source for Interferon beta-1b

{{short description|Cytokine in the interferon family}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 458271012
| image =

<!-- Clinical data -->
| tradename = Betaseron, Actoferon, Extavia
| Drugs.com = {{drugs.com|CONS|interferon_beta-1b}}
| MedlinePlus = a601151
| licence_EU = yes
| DailyMedID = Interferon_beta-1b
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_category =  
| routes_of_administration = [[Subcutaneous injection|Subcutaneous]]
| ATC_prefix = L03
| ATC_suffix = AB08
| ATC_supplemental =  

| legal_US = Rx-only
| legal_EU = Rx-only
| legal_status = Rx-only

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| bioavailability   = 
| protein_bound     = 
| metabolism        = 
| metabolites       = 
| onset             = 
| elimination_half-life = 
| duration_of_action = 
| excretion         = 

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 145155-23-3
| PubChem =  
| IUPHAR_ligand = 8340
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00068
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = TTD90R31WZ
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D00746
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201563
| NIAID_ChemDB      = 
| PDB_ligand        = 
| synonyms          = 

<!-- Chemical data -->
| IUPAC_name = Human interferon beta
| C=908 | H=1408 | N=246 | O=253 | S=6
}}
'''Interferon beta-1b''' is a [[cytokine]] in the [[interferon]] family used to treat the relapsing-remitting and secondary-progressive forms of [[multiple sclerosis]] (MS). It is approved for use after the first MS event. Closely related is [[interferon beta 1a]], also indicated for MS, with a very similar drug profile.

==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="Kieseier_2011">{{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="Kieseier_2011"/> Moreover, it is also thought to increase the production of [[nerve growth factor]] and consequently improve neuronal survival.<ref name="Kieseier_2011"/>

==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-1b is available only in injectable forms, and can cause skin reactions at the injection site that may include cutaneous [[necrosis]]. Skin reactions vary greatly in their clinical presentation.<ref name="Walther_1999"/> They usually appear within the first month of treatment albeit their frequence and importance diminish after six months of treatment.<ref name="Walther_1999"/> Skin reactions are more prevalent in women.<ref name="Walther_1999"/> 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="Walther_1999"/> Also over time, a visible dent at the injection site due to the local destruction of fat tissue, known as [[lipoatrophy]], may develop.

[[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='Eccles_2005'>{{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 = "Walther_1999" >{{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><ref name="Compston_2008">{{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> 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="Walther_1999"/> Another common transient secondary effect with interferon-beta is a functional deterioration of already existing symptoms of the disease.<ref name="Walther_1999"/> 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="Walther_1999"/> A symptom specially sensitive to worsening is [[spasticity]].<ref name="Walther_1999"/> 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="Walther_1999"/> In most cases these effects are non-dangerous and reversible after cessation or reduction of treatment.<ref name="Walther_1999"/> 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="Walther_1999"/>

The injection-site reactions can be mitigated by rotating injection sites or by using one of the medications that requires less frequent injections.  Side effects are often onerous enough that many patients ultimately discontinue taking Interferons (or [[glatiramer acetate]], a comparable disease-modifying therapies requiring regular injections).

==Efficacy==

=== 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]] but the patient does not fulfill the [[McDonald criteria|criteria]] for diagnosis of multiple sclerosis.<ref name="Miller_2005">{{cite journal | vauthors = Miller D, Barkhof F, Montalban X, Thompson A, Filippi M | title = Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis | journal = The Lancet. Neurology | volume = 4 | issue = 5 | pages = 281–288 | date = May 2005 | pmid = 15847841 | doi = 10.1016/S1474-4422(05)70071-5 | s2cid = 36401666 }}</ref> Treatment with [[interferon]]s after an initial attack decreases the risk of developing clinical definite MS.<ref name="Compston_2008"/><ref name='Bates_2011'>{{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 | pages = 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="Compston_2008"/> Interferons reduce relapses by approximately 30% and their safe profile make them the first-line treatments.<ref name="Compston_2008"/> 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="Bertolotto_2008">{{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="Bertolotto_2008"/> 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="Compston_2008"/> Moreover, a subset of RRMS patients with specially active MS, sometimes called "rapidly worsening MS" are normally non-responders to interferon beta-1b.<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="Compston_2008"/><ref name="Freedman_2011"/>  some data on the effects of interferons indicate that early-initiated long-term therapy is safe and it is related to better outcomes.<ref name="Freedman_2011">{{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>  More recent data suggest that interferon betas does not hasten disability.<ref name="Shirani_2012">{{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 = free }}</ref>

Interferon-β exacerbates Th17-mediated inflammatory disease.<ref name = "Axtell_2011">{{cite journal | vauthors = Axtell RC, Raman C, Steinman L | title = Interferon-β exacerbates Th17-mediated inflammatory disease | journal = Trends in Immunology | volume = 32 | issue = 6 | pages = 272–277 | date = June 2011 | pmid = 21530402 | pmc = 5414634 | doi = 10.1016/j.it.2011.03.008 }}</ref>

==Commercial formulations==
Betaferon/Betaseron is marketed today by [[Bayer|Bayer Pharma]]. The [[wikt:originator|originator]] was [[Schering AG]] ([[Berlex]] in North America), now part of Bayer Pharma. [[Novartis]] has also introduced Extavia, a new brand of interferon beta-1b, in 2009.

== References ==
{{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/interferon%20beta-1b | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Interferon beta-1b }}

{{Demyelinating diseases of CNS}}
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[[Category:Drugs developed by Bayer]]
[[Category:Cytokines]]
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