Slowing Down Long-Term Progression of Multiple Sclerosis With Disease-Modifying Therapies
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.
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). 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 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).
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 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.
Lemtrada and Novantrone carry special risks. Lemtrada is a humanized monoclonal therapy that binds to CD52, a protein found on mature lymphocytes. It 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 and it has been associated with increased risk of certain cancers and autoimmune thyroid disorders. 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 to 12 doses over two to three years due to an increased risk of heart damage and acute leukemia.
Seventeen disease-modifying therapies are approved for MS, as of April 2019:
- 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 Biogen and delivered by intramuscular injection once per week. Visit avonex.com or abovems.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. The 20 mg/mL dose is delivered by subcutaneous injection every day while the 40 mg/mL dose is given three days each week. 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.
- Glatiramer acetate injection is made by Mylan and delivered by subcutaneous injection every day or every three days. It is the generic version of Copaxone 20 mg/mL and 40 mg/mL, respectively. Visit glatirameracetate.com for more information.
- Glatopa (glatiramer acetate) is made by Sandoz/Novartis and delivered by subcutaneous injection every day or every three days. It is the generic version of Copaxone 20 mg/mL and 40 mg/mL, respectively. Visit glatopa.com for more information.
- Lemtrada (alemtuzumab) is made by Sandofi and delivered by intravenous infusion over 5 days and repeated over 3 days one year later. Visit lemtrada.com and MSOnetoOne.com for more information.
- Mavenclad (cladribine) is made by EMD Serono and taken by oral tablet during two courses of treatment separated by a year with each course divided into two cycles. The maximum cumulative dose is 3.25 mg/kg. Visit mavenclad.com for more information.
- Mayzent (siponimod) is made by Novartis and taken once daily as an oral tablet. Visit mayzent.com for more information.
- Novantrone (mitoxantrone) is made by EMD Serono and delivered by intravenous infusion once every 3 months with a lifetime maximum limit of 8-12 doses. Visit www.nationalmssociety.org for more information.
- Ocrevus (ocrelizumab) is made by Genentech and delivered by intravenous infusion twice a year with the first dose divided into two infusions. Visit ocrevus.com for more information.
- Plegridy (pegylated interferon beta-1a) is made by Biogen and delivered by subcutaneous injection every two weeks. It is chemically similar to Avonex. Visit plegridy.com or abovems.com 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 and delivered by intravenous infusion once every four weeks at a registered infusion center. Visit tysabri.com or abovems.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 therapies.