Personalized therapy for multiple sclerosis (MS)
Find out about available and emerging treatment therapies for multiple sclerosis (MS).By Mayo Clinic Staff
Multiple sclerosis (MS) is a chronic inflammatory central nervous system disease that causes bothersome or disabling physical symptoms, including problems with mobility, vision, coordination, cognitive function, fatigue and pain.
If you've been diagnosed with active or relapsing MS, your doctor may recommend immediate treatment with medications known as disease-modifying therapy (DMT). DMTs have been shown to affect the course of MS by reducing the number of relapses and delaying progression of disability to some degree.
Available DMTs differ with respect to how often they're taken, the method in which they're taken, their side effects and whether they can be taken during pregnancy. A thorough understanding of available and emerging DMTs can help you and your doctor form the best possible treatment strategy for your relapsing MS.
Currently, there are 10 Food and Drug Administration (FDA)-approved DMTs with varying degrees of effectiveness for reducing relapse risk and preserving neurological function.
Interferon beta drugs
These medications are among the first DMTs approved for relapsing MS and are still commonly first line options for treatment. These first generation therapies include the following four interferon beta medications:
- Avonex (interferon beta-1a)
- Betaseron (interferon beta-1b)
- Extavia (interferon beta-1b)
- Rebif (interferon beta-1a)
Known as immunomodulatory drugs, the exact mode of action of these medications is unknown, but interferon beta is thought to target various immune cells and proteins that play an important role in the inflammatory activity of MS.
The interferon beta medications are given by self-injection, either under the skin or in the muscle. The frequency of injections varies from one to three times weekly.
These drugs have comparable effectiveness, reducing the relapse rate by about one-third and slowing the development of new MS-related brain lesions for relapsing MS.
Flu-like symptoms and injection site reactions, such as redness and discomfort, are commonly reported side effects of interferon beta drugs.
Along with interferon beta drugs, glatiramer acetate (Copaxone) is considered to be a first line treatment option for relapsing MS. Exactly how glatiramer acetate works is unknown, though it's thought to stimulate immune system cells known as T cells. It may also have potential nerve-protecting effects.
Glatiramer acetate is given by self-injection under the skin, either three times weekly or every day. It is generally well-tolerated, but injection site reactions, such as redness and discomfort, are commonly reported.
Mitoxantrone is an immunosuppressive drug that's approved for treating rapidly worsening relapsing MS and the only medication approved to treat secondary progressive MS, an advanced form of relapsing MS.
At standard doses, use of mitoxantrone is limited to a maximum of two years because of important side effects, including damage to the heart muscle. A small number of patients who use mitoxantrone will later develop leukemia. Because of this, mitoxantrone is prescribed less often.
Natalizumab (Tysabri) is a humanized monoclonal antibody that is thought to act by reducing the migration of immune cells across the blood-brain barrier into the central nervous system. This medication is given intravenously every four weeks.
Natalizumab is effective against relapsing MS, reducing relapse rate by about two-thirds. However, it is associated with a small but important risk of a serious brain infection known as progressive multifocal leukoencephalopathy (PML).
People who take natalizumab must be closely monitored for symptoms of PML, which include progressive weakness and visual or cognitive changes that may not be reversible.
A person's ongoing PML risk is assessed using factors such as:
- The presence of antibodies to the John Cunningham virus on blood testing
- Previous treatment of immunosuppressive drugs, such as mitoxantrone
- Taking natalizumab longer than two years
Due to the PML risk, natalizumab is generally reserved for use in people whose MS can't be controlled with first line therapy use.
Three oral DMTs are approved for treating relapsing MS, including:
Fingolimod (Gilenya). This once-daily oral medication reduces the relapse rate by about 50 percent. Fingolimod is a unique medication that binds to many different types of body cells. It traps white blood cells in lymph nodes so that they cannot enter the brain and cause new MS lesions.
Fingolimod can't be used by individuals with heart disorders or related conditions. It temporarily slows the heart rate in almost everyone who takes it, so the first dose must be taken in a clinic under medical supervision. It also requires monitoring of visual function.
- Teriflunomide (Aubagio). Teriflunomide has been approved in two doses, 7 milligrams (mg) and 14 mg, taken once daily. While the higher dose is somewhat more effective, the lower dose may be more appropriate for people who may experience more side effects, such as headache, diarrhea, nausea, elevation in liver enzymes and hair thinning. Teriflunomide is known to be harmful to a developing fetus.
- Dimethyl fumarate (Tecfidera). Formerly known as BG-12, dimethyl fumarate (DMF) was recently approved for relapsing MS. Taken twice daily, DMF reduced relapse rates by about 50 percent in clinical trials. Common side effects include flushing and gastrointestinal problems that occur more frequently at the beginning of treatment, then steadily decrease over one to four weeks.
Drugs currently on the horizon for treatment of MS include:
June 20, 2014
Alemtuzumab (Campath). Another humanized monoclonal antibody, this intravenous drug is given in annual courses and has been associated with significant reductions in relapse rates, disability progression and disease activity.
Alemtuzumab is associated with serious adverse effects, especially secondary autoimmune disorders, such as autoimmune thyroid disease and idiopathic thrombocytopenic purpura. The FDA declined to approve alemtuzumab for MS in 2013, but the company that makes the drug has reapplied for approval.
- Ocrelizumab. This medication is a humanized immunoglobulin antibody currently being evaluated for treatment of relapsing MS. In initial studies, intravenous ocrelizumab reduced relapse rates and was well-tolerated. Further trials are underway.
- Laquinimod. Initial data on laquinimod, an oral medication, shows more modest effects on relapse rates and disease activity than currently approved DMTs. Further tests are being done to determine whether laquinimod has an advantage over other DMTs in regard to disability progression.
- Daclizumab (Zenapax). This humanized monoclonal antibody is associated with reduced relapse rates, disease activity and disability progression. Daclizumab seems to be well-tolerated. Side effects include respiratory infections and urinary tract infections.
- Wingerchuk DM, et al. Multiple sclerosis: Current and emerging disease-modifying therapies and treatment strategies. Mayo Clinic Proceedings. 2014;89:225.
- Weinstock-Guttman B. An update of new and emerging therapies for relapse-remitting multiple sclerosis. American Journal of Managed Care. 2013;19:S343.
- Treating MS: Medications. National Multiple Sclerosis Society. http://www.nationalmssociety.org/Treating-MS/Medications. Accessed May 17, 2014.
- Minagar A. Current and future therapies for multiple sclerosis. Scientifica. In press. Accessed May 17, 2014.
- Long-term treatments for MS. Multiple Sclerosis Association of America. http://www.mymsaa.org/about-ms/treatments/long-term/#chart. Accessed May 17, 2014.
- Wingerchuk DM (expert opinion). Mayo Clinic, Scottsdale, Ariz. June 7, 2014.