Choosing a Disease Modifying Therapy (DMT) to Use for Multiple Sclerosis

James Bowen, MD, Medical Director, Multiple Sclerosis Center

Swedish Neuroscience Institute, Seattle, WA

Dennis Bourdette, MD, Co-Director VA MS Center of Excellence, West
Portland VA Medical Center, Oregon Health and Science University

What are the current DMTs for MS?

Glatiramer acetate (Copaxone)

Interferon beta-1b (Betaseron, Extavia)

Interferon beta-1a (Rebif)

Interferon beta-1a (Avonex)

Natalizumab (Tysabri)

Mitoxantrone (Novantrone)
Fingolimod (Gilenya)

How do you decide? 

DMT Chart

What are the current DMTs for MS?

There are presently five injectable disease modifying therapies (DMTs), two infusion therapies, and one oral therapy that are FDA approved for the treatment of relapsing MS. The injectables include four forms of human recombinant interferon-beta (Avonex®, Betaseron® Extavia® and Rebif®) and a polypeptide, glatiramer acetate (Copaxone®). Two forms of infusion therapies include natalizumab (Tysabri®) that was re-released in late 2006 (is only available under an FDA mandated special restricted distribution program called TOUCH™), and a chemotherapy drug, mitoxantrone (Novantrone®) which is also registered to treat relapsing and secondary progressive MS. In general, Tysabri® and Novantrone® are second line therapies for most patients because of their side effects. The first oral medication is called fingolimod (Gilenya®). All DMTs have been shown to decrease MS disease activity in comparison with placebo. There are no well-designed, long term (> 2 years) randomized, double-blind comparison trials to help decide which, if any, of these drugs is the "best" treatment. There also is no consensus among MS experts about which agent is the "best," although many physicians who treat MS patients preferentially use one or two of the medications.

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• Glatiramer acetate (Copaxone®) is given at a dose of 20 mg s.c. once a day. It is not an interferon and does not have the "flu-like" side-effects that occur with the interferons. The most common side-effects are injection site reactions. These consist of erythema and induration. Some patients will develop lipoatrophy at injection sites. About 15% of patients will have an idiosyncratic immediate post-injection reaction characterized by flushing, chest pain, shortness of breath and anxiety. These spells generally occur only once but occasionally will occur more than once. They are self-limited and do not require specific treatment. No laboratory abnormalities occur with glatiramer acetate so laboratory monitoring is not necessary. Return to top 
  
  

• Interferon beta-1b (Betaseron®, Extavia®) is given at a dose of 250 μg s.c. every other day. The most common side-effects are "flu-like" symptoms (fever, muscle aches, malaise) that typically last about 24 hours after the injection. These symptoms usually can be controlled with pre- and post-injection treatment with acetaminophen (1000 mg 4-6 hours) and/or naproxen (220-440mg bid). Patients typically stop having these side-effects after they have been on the medication for several weeks to months. Injection site reactions are common. These usually consist of mild erythema. Skin necrosis at some injection sites rarely occurs. Leukopenia and elevations in liver function tests occur in some patients. Patients should undergo a CBC with differential and liver function tests before starting therapy, within one to two months afterwards and then, periodically as needed. After the first year of therapy laboratory testing should be repeated every 6 months. Betaseron® and Extavia® may occasionally increase depression. Women planning to become pregnant should not be taking Betaseron® or Extavia® as it can increase the risk of spontaneous abortions. There are no known drug interactions. Return to top
  
  

• Interferon beta-1a (Rebif®) is given at a dose of 44 μg s.c. three times a week on alternate days (e.g.. Monday, Wednesday, Friday). The most common side-effects are "flu-like" symptoms (fever, muscle aches, malaise) that typically last about 24 hours after the injection. These symptoms usually can be controlled with pre- and post-injection treatment with acetaminophen (1000 mg 4-6 hours) and/or naproxen (220-440mg bid). Patients typically stop having these side-effects after they have been on the medication for several weeks to months. Injection site reactions are also common. These usually consist of mild erythema. Skin necrosis at some injection sites rarely occurs. Leukopenia and elevations in liver function tests occur in some patients. Patients should undergo a CBC with differential and liver function tests before starting therapy, within one to two months afterwards and then, periodically as needed. After the first year of therapy laboratory testing should be repeated every 6 months. Rebif® may occasionally increase depression. Women planning to become pregnant should not be taking Rebif® as it can increase the risk of spontaneous abortions. There are no known drug interactions. Return to top
  
  

• Interferon beta-1a (Avonex®) is given at a dose of 30 μg im once a week. The most common side-effects are "flu-like" symptoms (fever, muscle aches, malaise) that typically last about 24 hours after the injection. These symptoms usually can be controlled with pre- and post-injection treatment with acetaminophen (1000 mg 4-6 hours) and/or naproxen (220-440mg bid). Patients typically stop having these side-effects after they have been on the medication for several weeks to months. Mild leukopenia and mild elevations in liver function tests occur in some patients. Patients should undergo a CBC with differential and liver function tests before starting therapy, one month afterwards and then every three months for the first year. After the first year of therapy laboratory testing should be repeated every 6 months. Avonex® may occasionally increase depression. Women planning to become pregnant should not be taking Avonex® as it can increase the risk of spontaneous abortions. There are no known drug interactions.Return to top
  
  

• Natalizumab (Tysabri®) is only available for prescribers that are registered in the TOUCH™ Prescribing Program. The recommended dose is 300 mg IV infusion every four weeks, with each dose being infused over approximately one hour. It is a recombinant humanized monoclonal antibody and is indicated for the treatment of patients with relapsing forms of MS to reduce the frequency of clinical exacerbations. It is known to be associated with hypersensitivity reactions including serious systemic reactions like anaphylaxis (less than 1%) and flu-like symptoms and urticaria generally occurring two hours after the infusion. Natalizumab increases the chance of getting a rare brain disorder that usually causes death or severe disability, called progressive multifocal leukoencephalopathy (PML). There is no known treatment or cure for PML. Return to top
  
  

• Mitoxantrone (Novantrone®) is given at a dose of 12 mg/M2 intravenously over 15-30 minutes every 3 months. This is generally done in an infusion center. It is a chemotherapy treatment that decreased the activity of the immune system. Side effects include damage to the heart muscle (requiring measurement of heart function before each dose) and rare cases of leukemia. More minor side effects include an increased risk of infection for several days after each infusion, and mild nausea, hair thinning, cessation of menstruation, and blue discoloration. A total lifetime dose of 140mg/M2 should not be exceeded.
  
  
• Fingolimod (Gilenya® ) is the first oral agent approved by the FDA in 2010 as a disease modifying treatment for MS. It is given at a dose of .5mg capsule taken once per day by mouth with or without food. It is a new class of MS medication called a sphingosine 1-phosphate receptor modulator. The medication mechanism of action can reduce neurodegeneration by reducing inflammatory damage to nerve cells. Side effects patients may develop include bradycardia, atrioventricular block, hypotension and other cardiac manifestations. Patients must be followed closely during the first 6 hours after an initial dose to recognize and treat these events if they occur. Other adverse events which require further investigation include development of macular edema, neoplasms and infections. Individuals who have questions about Fingolimod (Gilenya) should contact their healthcare provider or call the Novartis patient support line at 1 800 GILENYA (800 445-3692). Return to top
  
  

How do you decide?

There are many factors that go into deciding which medication to start for an individual patient. Things to consider are patient preference regarding injection frequency, concerns about "flu-like" side-effects, presence of co-morbidities, such as depression and epilepsy, ease of blood test monitoring and physician assessment of relative efficacy among the agents. Many patients choose a medication based on various differences between the treatments. Several of these are listed in the following table. Further details can be found under separate listing for each medication.
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DMT Chart (injectable and infusion therapies)

 

DMT Chart (oral therapies)

 

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Last Updated: April 2012