Slowing Down the Long-Term Progression of Multiple Sclerosis by Using Disease-Modifying Therapies (DMTs)

  • Effective treatment of multiple sclerosis involves a combination of therapeutic strategies. These are designed to help manage relapses, to manage MS symptoms, and to alter the disease course. It may also be important to take care of your body and mind through rehabilitation and psychosocial support.  

    Relapses are often treated with high-dose corticosteroids and lots of rest.  Depending upon the nature of your MS symptoms, you may want to use drug treatments, complementary and alternative therapies (including massage and acupuncture), rehabilitative approaches (including physical therapy and occupational therapy), and mental health services.

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    To alter the course of the disease, a number of disease-modifying therapies (DMTs) are available which are designed to help slow down the long-term progression of MS.  These treatments, or disease-modifying agents, have been shown in clinical trials to be effective in decreasing the frequency of relapses and the number of lesions in the brain or spinal cord.  Some of these medications have also been shown to slow down the rate at which a person with MS accumulates disability.  Using DMTs is one way to fight back against MS.  

    Currently available 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).  At this time, however, DMTs have not proven to be effective in progressive forms of MS.

    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.

    Injectable disease-modifying therapies which are considered to be first-line options include Avonex (interferon beta-1a), Rebif (interferon beta-1a), Betaseron (interferon beta-1b), Extavia (interferon beta-1b), and Copaxone (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.

    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 the most recently approved medication for MS and is in a class of drugs called Nrf2 activators believed to have anti-inflammatory and cytoprotective properties.


  • Infusible therapies include Tysabri (natalizumab) and Novatrone (mitoxantrone) which are both typically reserved as second-line treatment choices.  Tysabri, a humanized monoclonal antibody which binds to α4β1-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).  Novantrone is an anticancer drug which is approved for worsening RRMS, SPMS, and PRMS.  It is given 4 times per year by IV infusion but carries a lifetime cumulative dose limit of approximately 8-12 doses over 2-3 years due to an increased risk of heart damage and acute leukemia.

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    Another infusible therapy, Lemtrada (alemtuzumab), has been approved in Europe for use in MS, but is under review in the US and has not been approved yet by the FDA as of November 13, 2013.  Lemtrada (also known as Campath) is a humanized monoclonal therapy which binds to CD52, a protein found on mature lymphocytes, and is administered as IV infusion on 5 consecutive days followed by 3 infusions one year later.  Once Lemtrada has been given, there is no known way to remove it from one’s immune system.

    • Aubagio (teriflunomide) is made by Sanofi Genzyme and taken once daily as an oral tablet. Visit aubagio.com or MSOnetoOne.com for more information.
    • Avonex (interferon beta-1a) is made by BiogenIdec and delivered by intramuscular injection once per week. Visit avonex.com or msactivesource.com for more information.
    • Betaseron (interferon beta-1b) is made by Bayer Healthcare and delivered by subcutaneous injection every other day.  Visit betaseron.com for more information.
    • Copaxone (glatiramer acetate) is made by Teva Neuroscience and delivered by subcutaneous injection every day.  Visit copaxone.com or sharedsolutions.com for more information.
    • Extavia (interferon beta-1b) is made by Novartis and delivered by subcutaneous injection every other day.  It is chemically the same as Betaseron.  Visit extavia.com for more information.
    • Gilenya (fingolimod) is made by Novartis and taken once daily as an oral capsule.  Visit gilenya.com for more information.
    • Novantrone (mitoxantrone) is made by Serono and delivered by intravenous infusion once every 3 months with a lifetime maximum limit of 8-12 doses.  Visit http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/medications/mitoxantrone/index.aspx for more information.
    • Rebif (interferon beta-1a) is made by Serono and delivered by subcutaneous injection three days each week.  It is chemically similar to Avonex.  Visit rebif.com or mslifelines.com for more information.
    • Tecfidera (dimethyl fumarate) is made by Biogen Idec and taken as an oral capsule twice daily.  Visit tecfidera.com or msactivesource.com for more information.
    • Tysabri (natalizumab) is made by Biogen Idec and delivered by intravenous infusion once every four weeks at a registered infusion center.  Visit tysabri.com or msactivesource.com for more information.

    The choice to use a disease-modifying therapy (DMT) is a very personal one.  Here’s what the National MS Society has to say on the matter: “Many factors will influence the decision that you and your physician make about your choice of medication. One of them will be lifestyle issues that could affect your ability to stay with a treatment over time. Another factor is your response to the therapy, which should be carefully tracked. If your MS is not responding, you and your physician should discuss your options.”

  • Download the latest NMSS brochure on MS disease-modifying medications at http://goo.gl/fYosfA.

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    Lisa Emrich is author of the blog Brass and Ivory: Life with MS and RA and founder of the Carnival of MS Bloggers.

     

Published On: November 20, 2013