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Trade names | Betaseron, Actoferon, Extavia |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
MedlinePlus | a601151 |
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Routes of administration | Subcutaneous |
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ECHA InfoCard | 100.207.515 |
Chemical and physical data | |
Formula | C908H1408N246O253S6 |
Molar mass | 20011.08 g·mol−1 |
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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.
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. [1] Overall, therapy with interferon beta leads to a reduction of neuron inflammation. [1] Moreover, it is also thought to increase the production of nerve growth factor and consequently improve neuronal survival. [1]
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. [2] They usually appear within the first month of treatment albeit their frequence and importance diminish after six months of treatment. [2] Skin reactions are more prevalent in women. [2] Mild skin reactions usually do not impede treatment whereas necroses appear in around 5% of patients and lead to the discontinuation of the therapy. [2] Also over time, a visible dent at the injection site due to the local destruction of fat tissue, known as lipoatrophy, may develop.
Interferons, 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, muscle aches, fatigue, and headaches. [3] 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. [2] [4] This reaction tends to disappear after 3 months of treatment and its symptoms can be treated with over-the-counter nonsteroidal anti-inflammatory drugs, such as ibuprofen, that reduce fever and pain. [2] Another common transient secondary effect with interferon-beta is a functional deterioration of already existing symptoms of the disease. [2] 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. [2] A symptom specially sensitive to worsening is spasticity. [2] Interferon-beta can also reduce numbers of white blood cells (leukopenia), lymphocytes (lymphopenia) and neutrophils (neutropenia), as well as affect liver function. [2] In most cases these effects are non-dangerous and reversible after cessation or reduction of treatment. [2] Nevertheless, recommendation is that all patients should be monitored through laboratory blood analyses, including liver function tests, to ensure safe use of interferons. [2]
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).
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 criteria for diagnosis of multiple sclerosis. [5] Treatment with interferons after an initial attack decreases the risk of developing clinical definite MS. [4] [6]
Medications are modestly effective at decreasing the number of attacks in relapsing-remitting multiple sclerosis [7] and in reducing the accumulation of brain lesions, which is measured using gadolinium-enhanced magnetic resonance imaging (MRI). [4] Interferons reduce relapses by approximately 30% and their safe profile make them the first-line treatments. [4] Nevertheless, not all the patients are responsive to these therapies. It is known that 30% of MS patients are non-responsive to Beta interferon. [8] They can be classified in genetic, pharmacological and pathogenetic non-responders. [8] 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. [4] Moreover, a subset of RRMS patients with specially active MS, sometimes called "rapidly worsening MS" are normally non-responders to interferon beta-1b. [9] [10]
While more studies of the long-term effects of the drugs are needed, [4] [11] some data on the effects of interferons indicate that early-initiated long-term therapy is safe and it is related to better outcomes. [11] More recent data suggest that interferon betas does not hasten disability. [12]
Interferon-β exacerbates Th17-mediated inflammatory disease. [13]
Betaferon/Betaseron is marketed today by Bayer Pharma. The 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.
Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.
Multiple sclerosis (MS) is an autoimmune disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, vision loss, eye pain, muscle weakness, and loss of sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks or building up over time. In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. In the progressive forms of MS, bodily function slowly deteriorates and disability worsens once symptoms manifest and will steadily continue to do so if the disease is left untreated.
Interferon beta-1a is a cytokine in the interferon family used to treat multiple sclerosis (MS). It is produced by mammalian cells, while interferon beta-1b is produced in modified E. coli. Some research indicates that interferon injections may result in an 18–38% reduction in the rate of MS relapses.
Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients.
Natalizumab, sold under the brand name Tysabri among others, is a medication used to treat multiple sclerosis and Crohn's disease. It is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. It is given by intravenous infusion. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood–brain barrier.
Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia and multiple sclerosis. In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment. It is given by injection into a vein.
Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that affects the central nervous system (CNS). Several therapies for it exist, although there is no known cure.
Glatiramer acetate, sold under the brand name Copaxone among others, is an immunomodulator medication used to treat multiple sclerosis. Glatiramer acetate is approved in the United States to reduce the frequency of relapses, but not for reducing the progression of disability. Observational studies, but not randomized controlled trials, suggest that it may reduce progression of disability. While a conclusive diagnosis of multiple sclerosis requires a history of two or more episodes of symptoms and signs, glatiramer acetate is approved to treat a first episode anticipating a diagnosis. It is also used to treat relapsing-remitting multiple sclerosis. It is administered by subcutaneous injection.
Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.
Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds.
Research in multiple sclerosis may find new pathways to interact with the disease, improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.
Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.
Fred D. Lublin is an American neurologist and an authority on the treatment of multiple sclerosis. Along with colleagues at the National Multiple Sclerosis Society, his work redefined the clinical course definitions of MS.
Current standards for diagnosing multiple sclerosis (MS) are based on the 2018 revision of McDonald criteria. They rely on MRI detection of demyelinating lesions in the CNS, which are distributed in space (DIS) and in time (DIT). It is also a requirement that any possible known disease that produces demyelinating lesions is ruled out before applying McDonald's criteria.
Ponesimod, sold under the brand name Ponvory, is a medication for the treatment of multiple sclerosis. It is a sphingosine-1-phosphate receptor modulator.
Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars (scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions.
There are several ways for pharmaceuticals for treating multiple sclerosis (MS) to reach the market.
Rhonda Renee Voskuhl is an American physician, research scientist, and professor. She is a member of the Brain Research Institute (BRI) at the David Geffen School of Medicine at UCLA and is the director of its Multiple Sclerosis Program. Voskuhl has published numerous scientific articles in academic journals and has served in the role of principal investigator for several treatment trials investigating potential treatments for multiple sclerosis (MS).
Several biomarkers for diagnosis of multiple sclerosis, disease evolution and response to medication are under research. While most of them are still under research, there are some of them already well stablished: