Interferon beta 1a …

K K Jain MD†

Neuropharmacology & Neurotherapeutics

Updated 03.08.2021
Released 02.23.1999
Expires For CME 03.08.2024

Interferon beta 1a

Author: K K Jain MD†

See Contributor Disclosures

Interferon beta 1a

In This Article

Quick Link

Introduction

Historical note and terminology

Interferons are glycoproteins secreted in the body in response to viral infections and are presumed to provide protection to other cells against viral infection. The name derives from the term "viral interference" used in the first description of these proteins by their discoverers (24). In addition to the antiviral properties, immunomodulatory and antineoplastic properties of interferons were discovered later (04). Use of interferons in multiple sclerosis was based on the belief that the disease may be due to a latent virus infection of the brain in persons with impairment of the immune system (11). Trials with interferon have been conducted in various diseases of the nervous system including multiple sclerosis (15). Two types of interferons have been identified: type 1 (interferon alpha and interferon beta) and type 2 (interferon gamma). Type 2 is synthesized mainly by lymphocytes and type 1 beta by fibroblasts, but both have a similar amino acid composition and genetic coding. Gamma interferon differs from type 1 interferons by its amino acid composition and cell surface receptor. Interferon alpha has been developed mostly for applications in virology and oncology. Interferon beta has a beneficial effect on the course of multiple sclerosis, and interferon alpha has an equivocal effect, whereas interferon gamma exacerbated the disease. Reasons for these various effects are not well understood. History of development of interferon beta therapy for multiple sclerosis has been reviewed elsewhere (41). Descriptions in this article are based on interferon beta 1a and a separate article is devoted to interferon beta 1b.

Interferons are now manufactured commercially in large quantities by recombinant DNA technology. United States Food and Drug Administration approved interferon beta 1a for intramuscular injection in 1996 (Avonex by intramuscular injection). Another preparation of interferon beta 1a for subcutaneous injection was approved in the United States in 2002 (Rebif by subcutaneous injection).

The amino acid sequence of Avonex (R) is identical to that of natural human interferon beta. It cannot be compared with other interferon betas because of the differences in reference standards. Moreover, the route of administration affects the action, and intramuscular preparation is distinct from the subcutaneous injection preparation. Both preparations have been compared in clinical trials.

Pharmacology

Interferons are cytokines that mediate antiviral, antiproliferative, and immunomodulatory activities in response to viral infections and other biological inducers.

Pharmacodynamics. Interferon beta exerts its effect by binding to specific receptors on human cells. This leads to a complex chain of events that, in turn, leads to expression of various interferon-induced gene products. The exact mechanism of action is not fully understood, but the following actions are believed to contribute to its beneficial effects in multiple sclerosis:

	• Direct effect on plasma cells modulating IgG synthesis, which is increased within the blood-brain barrier in patients with multiple sclerosis.
	• Increase of cerebrospinal fluid levels of interleukin-10 in patients with multiple sclerosis.
	• Inhibition of interleukin 1 beta and tumor necrosis factor alpha.
	• Stimulation of interleukin 1 receptor antagonist production in human peripheral blood mononuclear cells.
	• Stimulation of lymphocytes to produce normal amounts of interferon.
	• Inhibition of proliferation of leukocytes.
	• Decreased antigen presentation in microglia.
	• Restoration of metabolites in multiple sclerosis lesions as demonstrated by magnetic resonance spectroscopy imaging.
	• Anti-inflammatory effects via T cells:
	(1) Reduction of T cell migration by inhibition of the activity of T cell matrix metalloproteinases.
	(2) Down regulation of adhesion molecules. Interferon beta-induced increase in soluble vascular cell adhesion molecule-1 may lead to a decrease in later antigen-4 expression, which mediates migration of T cells into the nervous system.
	(3) Decreased interferon gamma secretion.

Pharmacokinetics. Important features are:

	• Following an intramuscular dose, serum levels of interferon beta 1a peak between 3 and 15 hours.
	• Elimination half-life is 10 hours.
	• Systemic exposure is greater following intramuscular injection than following subcutaneous injection as determined by area under the curve and Cmax values.

A patient who presented with acute onset of multiple sclerosis with tumefactive brain lesions and concomitant hepatitis C virus 2a/2C infection was reported to have dual benefit of long-term interferon beta 1a therapy (34). Interferon beta 1a is also effective against hepatitis C virus 2a/2c infection, which may be involved in triggering autoimmune tumefactive brain lesions.

Methods of administration. Interferon beta 1a is administered by intramuscular or subcutaneous injection (see Clinical trials section). RebiSmart, an electronic autoinjector for the subcutaneous administration of interferon beta 1a (Rebif), offers several advantages, including adjustable injection settings and a hidden needle to avoid needle phobia as well as reduce the risk of needle stick injury, which may improve compliance (33).

Interferon beta 1a is being PEGylated, ie, attached with polyethylene glycol, to improve safety as well as effectiveness. Data from clinical trials suggest that it should provide a more convenient dosing regimen (29). On February 1, 2021, intramuscular injection peginterferon beta-1a (trade name PLEGRIDY) was approved for clinical use in the United States and the European Union. The FDA’s approval of intramuscular administration for PLEGRIDY is based on data evaluating bioequivalence and fewer injection site adverse reactions associated with intramuscular administration compared to subcutaneous administration in healthy volunteers. PLEGRIDY has been proven to significantly reduce the relapse rate in multiple sclerosis and slow the progression of disability as well as reduce the number of brain lesions.

Pharmacogenomics. Intramuscular interferon beta 1a therapy induces transcriptional effects in patients with relapsing-remitting form of multiple sclerosis and several genes are up- or downregulated. A sub-network of genes centered on NF-κB is highly expressed in patients likely to develop interferon beta-related side effects (22).

Clinical trials

Since 1995, several randomized, double-blind, placebo-controlled clinical trials have been conducted with interferon beta 1a in patients with active relapsing multiple sclerosis and have shown reduction of lesions shown on MRI scans as well as disability progression.

The clinical and brain MRI results of a randomized trial support initiating interferon beta 1a treatment at the time of a first episode of optic neuritis occurring in patients at high risk for multiple sclerosis based on the presence of subclinical brain MRI lesions (08).

The EVIDENCE trial (a randomized, controlled, multicenter trial) compared the efficacy and safety of interferon beta 1a (Rebif) 44 µg subcutaneously 3 times weekly and interferon beta 1a (Avonex) 30 µg IM once weekly in patients with relapsing remitting multiple sclerosis (36). Rebif was more effective than Avonex on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment. The crossover phase of the EVIDENCE study found that patients who changed from low-dose, once-weekly treatment to high-dose, 3-times-weekly treatment experienced enhanced benefits of treatment without a substantial increase in adverse events (39).

A randomized, double-blind, placebo-controlled trial has shown that early treatment with interferon beta 1a is effective in reducing conversion to clinically definite multiple sclerosis and in slowing progressive loss of brain tissue in patients with clinically isolated syndromes suggestive of multiple sclerosis (13).

A multicenter, randomized, double-blind, placebo-controlled, phase III study of weekly, low dose, subcutaneous interferon beta 1a in secondary progressive multiple sclerosis did not show any benefit for either disability or relapse outcomes (01). The results indicate that relapses in this phase of the disease may need treatment with higher doses than in the initial phases.

In the prevention of relapses and disability by interferon subcutaneously in multiple sclerosis (PRISMS) study, subcutaneous interferon beta 1a 3 times weekly for up to 4 years was well tolerated without dose-limiting safety concerns (18). An 8-year open-label extension study of the phase III trial of intramuscular interferon beta 1a showed that it was well tolerated with a low incidence of neutralizing antibodies (23).

The BENEFIT (BEtaseron/Betaferon in Newly Emerging multiple sclerosis For Initial Treatment) study incorporated pharmacogenetic and pharmacogenomic analyses to determine the genetic elements controlling multiple sclerosis (27). The data from this study suggest that early initiation of treatment with interferon beta 1b prevents the development of confirmed disability, supporting its use after the first manifestation of relapsing-remitting multiple sclerosis.

A post-hoc analysis of MRI data collected prospectively from the EVIDENCE study showed that patients with relapsing-remitting multiple sclerosis treated with interferon beta 1a, 44 mcg subcutaneously 3 times a week, had greater reduction in total volume of T2 lesions after 48 weeks than those treated with interferon beta 1a, 30 mcg intramuscularly 4 times a week; this was consistent with other clinical and MRI outcome measures (42).

A phase IIIb, open-label study of the new formulation of subcutaneous interferon beta 1a (Rebif New Formulation), which is produced without fetal bovine serum and human serum albumin as excipients, shows that it has improved immunogenicity and safety profiles compared with the original formulation (17). Results of another phase IIIb trial showed continued or increased levels of satisfaction with the new formulation of subcutaneous interferon beta 1a, because flu-like symptoms occurring with the new formulation were generally mild and seldom sufficiently bothersome to require ibuprofen treatment (07).

In the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study, subcutaneous interferon beta 1a significantly decreased MRI measures of disease with better cognitive outcomes for the 44 µg dose as compared to the 22 µg dose over a period of 3 years (03).

ADVANCE, a 2-year, double-blind, placebo-controlled, parallel group, phase 3 study on patients with relapsing-remitting multiple sclerosis showed that subcutaneous peginterferon beta 1a given once every 2 weeks or 4 weeks significantly reduced the relapse rate after 48 weeks of treatment (06). Results indicate that the drug may be effective with less frequent administration than practiced currently.

Analysis of a retrospective 2-year study on patients with relapsing-remitting multiple sclerosis who were randomized to intramuscular interferon beta 1a or placebo showed significantly less gray matter atrophy, but not white matter atrophy, was observed on MRI (14). Risk of sustained disability progression was significantly associated with gray matter but not white matter atrophy.

Patients who completed the 24-month double-blind REFLEX (REbif FLEXible dosing in early MS) study were enrolled in an extension (REFLEXION, REbif FLEXible dosing in early MS extensION). Over 5 years, in patients presenting with a first clinical demyelinating event, early subcutaneous interferon beta 1a thrice weekly administration versus delayed treatment prolonged time to clinically definite multiple sclerosis and reduced overall MRI activity (10).

Goals and duration of treatment

The aim is to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. It is not a curative treatment. The therapy can be continued for an indefinite period. Results of prolonged follow-up treatment of up to 8 years, including the years in clinical trials, indicate that patients with relapsing-remitting multiple sclerosis can experience sustained benefit over many years from early interferon beta 1a subcutaneous therapy 3 times weekly compared with patients whose treatment is delayed (28). Review of several studies shows that high-dose, high-frequency subcutaneous interferon beta 1a offers an effective option for treating patients with relapsing multiple sclerosis and has proven long-term safety and tolerability, as well as a favorable benefit-to-risk ratio compared with other forms of interferon beta (21). Considerable clinical data as well as real-life evidence support that interferon beta 1a is one of the best treatments for multiple sclerosis and that high-dose or frequent administration may provide better long-term outcomes (44).

In a large observational multiple sclerosis registry, treatment discontinuations were more common in patients on thrice weekly subcutaneous injections of interferon 22 µg beta -1a; however, 2-year clinical outcomes did not differ between patients receiving the different dosages (26). Results of the postmarketing study of interferon beta 1a intramuscular therapy for multiple sclerosis in Japan with a follow-up of 2 years show significant improvement in annualized relapse rate and expanded disability status scale, whereas the safety and effectiveness profile were consistent with those in previous reports (35). At 3 years follow-up, patients with relapsing-remitting multiple sclerosis who received subcutaneous interferon beta 1a did not have any active disease and had a lower percentage of annualized brain volume loss compared to patients with disease activity (37).

An immunometabolic biomarker profile is a useful tool to predict disease course in patients with relapsing-remitting multiple sclerosis during treatment with interferon beta 1a. Examples include the following (32):

	• Higher levels of interleukin-6, soluble CD40 ligand, and leptin at baseline indicate a higher relapse rate as well as a greater risk of experiencing at least 1 relapse in the following year.
	• Higher values of soluble tumor necrosis factor receptor and leptin at baseline predict a larger number of lesions in the following year.
	• Results of a study using interferon beta 1a subcutaneously 3 times a week as the first disease-modifying treatment for patients with relapsing multiple sclerosis identified young age, a short delay to treatment start, and slower disability progression as factors for better outcome (25).
	• A double-blind, placebo-controlled study has shown no evidence of disease activity with early treatment of subcutaneous interferon beta 1a, not only at 2, but also at 3 and 5 years (16).
	• In PRISMS-15 study (clinicaltrial.gov identifier: NCT01034644), MAGNIMS (magnetic resonance imaging in MS) score at year 1 predicted risk of clinical disease activity and confirmed disability progression in subcutaneous IFN β-1a-treated patients over up to 15 years (40). This helps to identify patients with likelihood of more active disease who may benefit from an adjustment of their treatment.

Special considerations

Caution should be exercised in giving interferon beta 1a to patients with depression and patients with seizure disorders. Patients with multiple sclerosis may develop depression and suicidal thoughts when treated with high doses of interferon beta 1a. Patients with cardiac disease should be closely monitored. All patients should have periodic blood chemistry and hematology tests.

Seizures may occur as an adverse effect of interferon beta and caution should be exercised when administering it to patients with a seizure disorder.

Anesthesia. No relevant information is available.

Pregnancy. Interferon beta 1a is contraindicated for pregnant women and should not be used unless the potential benefit justifies the potential risk to the fetus. However, a review of outcomes of women exposed to subcutaneous interferon beta 1a during pregnancy revealed normal live births (38). The rates of spontaneous abortion and major congenital anomalies in live births were in line with those observed in the general population.

Results of a study on women chronically receiving intramuscular interferon beta 1a suggest that interferon beta 1a does not enter the milk compartment significantly and that levels in milk are below those required to produce pharmacological effects (20). No side effects were observed in any of the breastfed infants.

Pediatric. Treatment with interferon beta 1a is well tolerated and may be effective in low doses of 15 micrograms once a week for early-onset multiple sclerosis in patients under the age of 16 years. A retrospective study that analyzed multinational pediatric patients with multiple sclerosis who received subcutaneous interferon beta 1a showed that those from the United States had higher body mass index, relapsed more frequently, and had shorter median interval from the first clinical demyelinating event to initiation of disease modifying therapy compared with adolescent patients in rest of world (31).

Geriatric. No relevant information is available.

Adverse effects

Adverse events reported during clinical trials and postmarketing experience are listed in the Physicians’ Desk Reference. Some of the adverse reactions are:

	• Flu-like symptoms, which include fever, chills, myalgias, and arthralgias. A combination of initial dose titration and analgesic administration is useful for the reduction of flu-like symptoms with interferon beta 1a therapy.
	• Injection-site reactions. These can be reduced by the use of an autoinjector.
	• Autoimmune disorders including autoimmune hepatitis and hepatic injury manifesting itself as elevated serum enzyme levels and hepatitis have been reported in postmarketing studies.
	• Subacute cutaneous lupus erythematosus has been reported due to treatment with interferon beta 1a (05).
	• Anaphylaxis has been reported as a rare complication of interferon beta use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria.
	• Detection of NAbs is usually a regulatory expectation. Cell-based assays are available for detection of anti-interferon-beta neutralizing antibodies, but all present technical difficulties and limitations. A non-cell-based assay, which overcomes the limitations of cell-based assays, has been described (09).
	• Interferon beta treatment for multiple sclerosis may be associated with thyroid disorders in patients with subclinical thyroid disease or antithyroid autoantibodies before starting treatment.
	• Interferon syndrome
	• Exacerbation of multiple sclerosis may occur in some cases. It is difficult to ascertain if this is the natural progression of the disease with a lack of efficacy of treatment or an adverse reaction to the drug.
	• Hematological abnormalities are common and dose-related in patients with multiple sclerosis receiving interferon beta 1a, but the events are mainly mild and transient.
	• Cases of nephrotic syndrome have been reported during Interferon beta 1a therapy. This complication usually resolves following discontinuation of the drug.
	• Severe acute autoimmune hepatitis (43)
	• Retinopathy with peripheral retinal hemorrhages has been reported in patients receiving interferon beta 1a, and it may be asymptomatic (02).

These reactions can be minimized by adjusting the dose and time of injection. Symptomatic management of the adverse effect includes use of steroids as well as nonsteroidal anti-inflammatory drugs. Other measures are use of analgesic or antipyretic drugs, proper injection technique, and modification of the dosage of interferon beta or discontinuation of the drug.

References

01: Andersen O, Elovaara I, Farkkila M, et al. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2004;75(5):706-10. PMID 15090564
02: Bakri SJ, Swanson JW. Asymptomatic peripheral retinal hemorrhages as a manifestation of interferon beta 1a retinopathy. Semin Ophthalmol 2015;30(1):56-7. PMID 23952180
03: Bastianello S, Giugni E, Amato MP, et al. Changes in magnetic resonance imaging disease measures over 3 years in mildly disabled patients with relapsing-remitting multiple sclerosis receiving interferon β-1a in the COGnitive Impairment in MUltiple Sclerosis (COGIMUS) study. BMC Neurol 2011;11:125. PMID 21999142
04: Borden EC, Ball LA. Interferons: biochemical, cell growth inhibitory and immunological effects. In: Brown EB, editor. Progress in hematology. New York: Grune & Stratton, 1981:299-339.
05: Buchanan S, Rosemergy I, Healy P. Drug-induced subacute cutaneous lupus erythematosus due to treatment with interferon beta-1a. N Z Med J 2013;126(1379):98-101. PMID 24045357
06: Calabresi PA, Kieseier BC, Arnold DL, et al. Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol 2014;13(7):657-65. PMID 24794721
07: Camu W, Hadjout K, Latour S, Pöhlau D, Masri S. Patient satisfaction following transition from the original to the new formulation of subcutaneous interferon beta-1a in relapsing multiple sclerosis: a randomized, two-arm, open-label, Phase IIIb study. Patient Prefer Adherence 2010;4:127-33. PMID 20517473
08: CHAMPS Study Group. Interferon beta-1a for optic neuritis patients at high risk for multiple sclerosis. Am J Ophthalmol 2001;132(4):463-71. PMID 11589865
09: Cludts I, Meager A, Thorpe R, Wadhwa M. Development and characterization of a non-cell-based assay to assess the presence of neutralizing antibodies to interferon-beta in clinical samples. J Immunol Methods 2013;395(1-2):37-44. PMID 23831137
10: Comi G, De Stefano N, Freedman MS, et al. Subcutaneous interferon β-1a in the treatment of clinically isolated syndromes: 3-year and 5-year results of the phase III dosing frequency-blind multicentre REFLEXION study. J Neurol Neurosurg Psychiatry 2017;88(4):285-94. PMID 28039317
11: Cook SD, Dowling PC. Multiple sclerosis and viruses: an overview. Neurology 1980;20:80-91. PMID 6248821
12: Davoudi-Monfared E, Rahmani H, Khalili H, et al. A randomized clinical trial of the efficacy and safety of interferon β-1a in treatment of severe COVID-19. Antimicrob Agents Chemother 2020;64(9):e01061-20. PMID 32661006
13: Filippi M, Rovaris M, Inglese M, et al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet 2004;364(9444):1489-96. PMID 15500893
14: Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing-remitting multiple sclerosis: a retrospective analysis. Mult Scler 2016;22(5):668-76. PMID 26238463
15: Fleishman WR, Ramamurthy V, Stanton JG, et al. Interferon: mode of action and clinical applications. In: Smith RA, editor. Interferon treatment in neurological disorders. New York: Marcel Dekker Inc, 1988:1-42.
16: Freedman MS, Comi G, Coyle PK, et al. No evidence of disease activity status in patients treated with early vs. delayed subcutaneous interferon β-1a. Mult Scler Relat Disord 2019;39:101891. PMID 31864098
17: Giovannoni G, Barbarash O, Casset-Semanaz F, et al; Rebif New Formulation Study Group. Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results. Mult Scler 2009;15(2):219-28. PMID 18755819
18: Gold R, Rieckmann P, Chang P, Abdalla J; PRISMS Study Group. The long-term safety and tolerability of high-dose interferon beta-1a in relapsing-remitting multiple sclerosis: 4-year data from the PRISMS study. Eur J Neurol 2005;12:649-56. PMID 16053475
19: Grimaldi LM, Zappalà G, Iemolo F, et al. A pilot study on the use of interferon beta-1a in early Alzheimer's disease subjects. J Neuroinflammation 2014;11:30. PMID 24524367
20: Hale TW, Siddiqui AA, Baker TE. Transfer of interferon β-1a into human breastmilk. Breastfeed Med 2012;7(2):123-5. PMID 21988602
21: Hartung HP. High-dose, high-frequency recombinant interferon beta-1a in the treatment of multiple sclerosis. Expert Opin Pharmacother 2009;10(2):291-309. PMID 19236200
22: Hecker M, Goertsches RH, Fatum C, et al. Network analysis of transcriptional regulation in response to intramuscular interferon-β-1a multiple sclerosis treatment. Pharmacogenomics J 2012;12(4):360. PMID 22825046
23: Herndon RM, Rudick RA, Munschauer FE 3rd, et al. Eight-year immunogenicity and safety of interferon beta-1a-Avonex treatment in patients with multiple sclerosis. Mult Scler 2005;11:409-19. PMID 16042223
24: Isaacs A, Lindemann J. Virus interference, I: the interferon. Proc R Soc Lond B Biol Sci 1957;147:258-67. PMID 13465720
25: Järvinen E, Murtonen A, Tervomaa M, Sumelahti ML. Interferon β-1a subcutaneously 3 times/week clinical outcome in relapsing multiple sclerosis in Finland. Neurol Int 2019;11(4):8177. PMID 31871598
26: Kalincik T, Spelman T, Trojano M, et al. Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis. PLoS One 2013;8(5):e63480. PMID 23704913
27: Kappos L, Freedman MS, Polman CH, et al; BENEFIT Study Group. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 2007;370(9585):389-97. PMID 17679016
28: Kappos L, Traboulsee A, Constantinescu C, et al. Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS. Neurology 2006;67(6):944-53. PMID 17000959
29: Kieseier BC, Calabresi PA. PEGylation of interferon-β-1a: a promising strategy in multiple sclerosis. CNS Drugs 2012;26(3):205-14. PMID 22201341
30: Konde MK, Baker DP, Traore FA, et al. Interferon β-1a for the treatment of Ebola virus disease: a historically controlled, single-arm proof-of-concept trial. PLoS One 2017;12(2):e0169255.** PMID 28225767
31: Krupp LB, Pohl D, Ghezzi A, et al. Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study. J Neurol Sci 2016;363:33-8. PMID 27000217
32: Lanzillo R, Carbone F, Quarantelli M, et al. Immunometabolic profiling of patients with multiple sclerosis identifies new biomarkers to predict disease activity during treatment with interferon beta-1a. Clin Immunol 2017;183:249-53. PMID 28823971
33: Lugaresi A. RebiSmart™ (version 1.5) device for multiple sclerosis treatment delivery and adherence. Expert Opin Drug Deliv 2013;10(2):273-83. PMID 23252744
34: Mader EC Jr, Richeh W, Ochoa JM, Sullivan LL, Gutierrez AN, Lovera JF. Tumefactive multiple sclerosis and hepatitis C virus 2a/2C infection: dual benefit of long-term interferon beta-1a therapy? J Neurol Sci 2015;349(1-2):239-42. PMID 25575859
35: Makioka H, Nakaya F, Ling Y, Torii S, Saida T, Kira JI. Safety and effectiveness of interferon β-1a intramuscular therapy: results of the postmarketing drug surveillance in Japan. Rinsho Shinkeigaku 2017;57(10):553-61. PMID 28966229
36: Panitch H, Goodin DS, Francis G, et al; EVIDENCE Study Group. EVidence of Interferon Dose-response: European North American Comparative Efficacy; University of British Columbia MS/MRI Research Group. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology 2002;59:1496-506. PMID 12451188
37: Rojas JI, Sanchez F, Caro F, et al. Brain volume loss and no evidence of disease activity over 3 years in multiple sclerosis patients under interferon beta 1a subcutaneous treatment. J Clin Neurosci 2019;59:175-8.** PMID 30401571
38: Sandberg-Wollheim M, Alteri E, Stam Moraga M, Kornmann G. Pregnancy outcomes in multiple sclerosis following subcutaneous interferon beta-1a Therapy. Mult Scler 2011;17(4):423-30. PMID 21220368
39: Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis. Clin Ther 2007;29(9):2031-48. PMID 18035202
40: Sormani MP, Freedman MS, Aldridge J, Marhardt K, Kappos L, De Stefano N. MAGNIMS score predicts long-term clinical disease activity-free status and confirmed disability progression in patients treated with subcutaneous interferon beta-1a. Mult Scler Relat Disord 2021;49:102790. PMID 33571946
41: Stock G, Horowski R. A short history of beta-interferon therapy of multiple sclerosis [Article in German]. Med Klin (Munich) 2001;96(Suppl 1):3-9. PMID 11603113
42: Traboulsee A, Al-Sabbagh A, Bennett R, Chang P, Li DK; EVIDENCE Study Group; UBC MS/MRI Research Group. Reduction in magnetic resonance imaging T2 burden of disease in patients with relapsing-remitting multiple sclerosis: analysis of 48-week data from the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) study. BMC Neurol 2008;8:11. PMID 18426595
43: Villamil A, Mullen E, Casciato P, Gadano A. Interferon beta 1a-induced severe autoimmune hepatitis in patients with multiple sclerosis: report of two cases and review of the literature. Ann Hepatol 2015;14(2):273-80. PMID 25671839
44: Zettl UK, Hecker M, Aktas O, Wagner T, Rommer PS. Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge. Expert Rev Clin Immunol 2018;14(2):137-53. PMID 29318902

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Interferon beta 1a

Other Pertinent Drugs

interferon beta 1b
mitoxantrone
natalizumab

Also Relevant

Autoantibodies
Chronic inflammatory demyelinating polyradiculoneuropathy
Clinical trials in multiple sclerosis
Motor and multifocal motor neuropathies
Multiple sclerosis
- Multiple sclerosis: neurobehavioral aspects
- Natalizumab
- Neurologic complications of chemotherapy
- Neuropharmacology
- Optic neuritis
- Treatment of multiple sclerosis symptoms

Clinical Categories

Web References

Guidelines

AAN: Neutralizing antibodies to Interferon-beta: clinical and radiographic Impact

	• Basal cell cancer, Phase III, United States
	• Cystic fibrosis, Phase II, United States
	• Hepatitis B, Phase III completed, United States
	• Hepatitis C, Phase III completed, United States
	• Human papilloma virus infections leading to cervical dysplasia, Phase III completed, United States
	• Interferon beta 1a has Orphan Drug status in the Unites States for the treatment of cutaneous T cell lymphoma, cutaneous malignant melanoma, and AIDS-related Kaposi sarcoma.
	• Non small-cell lung cancer, Phase-III, European Union
	• Colorectal cancer, Phase-III, European Union
	• Multifocal motor neuropathy
	• Ulcerative colitis
	• Recurrent nephrotic syndrome in patient with multiple sclerosis
	• Chronic inflammatory demyelinating polyradiculoneuropathy
	• Guillain-Barré syndrome
	• A double-blind, randomized, placebo-controlled, multicenter pilot study on patients with early Alzheimer disease showed significant improvements in the Instrumental Activities of Daily Living and Physical Self-maintenance Scale (19).
	• Ebola virus disease (30)
	• A randomized placebo-controlled clinical trial showed that treatment with interferon β-1a reduced mortality of severe COVID-19 (12).

Interferon beta 1a …

Interferon beta 1a

Introduction

Historical note and terminology

Pharmacology

Clinical trials

Indications

Off-label uses

Contraindications

Goals and duration of treatment

Dosing

Special considerations

Interactions

Adverse effects

References

Contributors

Author

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Giant cell arteritis

Acupuncture

Chronic inflammatory demyelinating polyradiculoneuropathy

Autoimmune autonomic neuropathy

HTLV-1 associated myelopathy

Myositis and cancer

Interferon beta 1a

Introduction

Historical note and terminology

Pharmacology

Clinical trials

Indications

Off-label uses

Contraindications

Goals and duration of treatment

Dosing

Special considerations

Interactions

Adverse effects

References

Contributors

Author

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Giant cell arteritis

Acupuncture

Chronic inflammatory demyelinating polyradiculoneuropathy

Autoimmune autonomic neuropathy

HTLV-1 associated myelopathy

Myositis and cancer

This is an article preview.
Start a Free Account
to access the full version.