Wednesday, January 3, 2018

Using Disease-Modifying Therapies to Slow Down Multiple Sclerosis

Currently available disease-modifying therapies (DMTs) are primarily used in relapsing forms of the disease, including relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS) in patients still having relapses, and progressive-relapsing MS (PRMS). Some DMTs are also approved for delaying a second exacerbation in people who have been diagnosed with clinically isolated syndrome (CIS). One DMT has been approved for primary progressive MS (PPMS).

Disease-modifying therapies (DMTs) can be grouped together in a variety of ways. They can be categorized as oral drugs, self-injectables, or infusible medications; or they may be identified by their mechanism of action (MOA, or how they work). DMTs can also be divided into so-called first-line agents, which are common initial treatment choices for people diagnosed with MS, or second-line agents, which are typically reserved for patients who have not responded adequately or are unable to tolerate first-line drugs.

Self-injectable DMTs

Self-injectable disease-modifying therapies considered to be first-line options include Avonex (interferon beta-1a), Rebif (interferon beta-1a), Betaseron (interferon beta-1b), Extavia (interferon beta-1b), Copaxone (glatiramer acetate), and Glatopa (glatiramer acetate). Interferon beta drugs are FDA- approved to treat all relapsing forms of MS. With the exception of Rebif, interferon beta drugs are also approved for use in CIS. Copaxone is a synthetic polypeptide agent which is approved for RRMS and CIS. An additional injectable medication includes Plegridy (pegylated interferon beta-1a).

Oral DMTs

Since 2010, three oral therapies, each with different mechanisms of action, have been approved by the FDA for treatment of relapsing forms of MS. Gilenya (fingolimod) is the first in a new class of oral MS medications, called sphingosine 1-phosphate receptor modulators, which suppress lymphocyte circulation in the immune system. Two other agents in this class are currently in clinical trials. Aubagio (teriflunomide) is also the first in a new class of oral MS medications called pyrimidine synthesis inhibitors which have anti-inflammatory and immunoregulatory properties that have been used to treat rheumatoid arthritis and psoriatic arthritis. Tecfidera (dimethyl fumarate) is in a class of drugs called Nrf2 activators believed to have anti-inflammatory and cytoprotective properties.

Intravenous DMTs

Intravenous therapies include Tysabri (natalizumab), Ocrevus (ocrelizumab), Lemtrada (alemtuzumab), and Novatrone (mitoxantrone) which are typically reserved as second-line treatment choices. Tysabri, a humanized monoclonal antibody that binds to alpha-4 integrin and inhibits T-cells from crossing the blood-brain-barrier, is administered every 4 weeks by specially trained healthcare providers. Tysabri is approved for relapsing forms of MS and is highly effective, but carries the risk of a serious brain infection called progressive multifocal leukoencephalopathy (PML). Ocrevus, a humanized monoclonal antibody that binds to and depletes CD20+ B-cells, is administered twice a year with the first dose split into two infusions. Ocrevus is associated with infusion-related reactions and increased risk of breast cancer.

Read this post in its entirety:

Slowing Down Long-Term Progression of Multiple Sclerosis With Disease-Modifying Therapies

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