14 August, 2017
Drugs and Treatment for Multiple Sclerosis
Recent developments in MS medications have brought in much-needed new treatment options for patients and physicians. The advantage of having multiple medications allows us to create a more tailored treatment for each patient and pay closer attention to individual needs.
Two different treatment strategies are used for MS at different points: treatment of acute relapse and long-term preventative treatment.
Acute Relapse Treatment
The acute relapse is usually treated with steroids, most often given intravenously or as an oral regimen. High doses of steroids are used daily for few days, and the main goal of this treatment is to stop acute ongoing inflammation. Steroids do not affect MS itself, but they will decrease the duration and severity of relapse symptoms.
As a result of this treatment, neurological symptoms like weakness or numbness either resolve completely or improve significantly. This can be seen during the treatment course, and improvement often continues for many months afterward. It is important to know that every relapse will eventually stop, whether or not steroids are administered. So not every relapse will necessarily need treatment with steroids, and physicians may choose to treat only a relapse with significant functional impairment.
Oral treatment with steroids usually takes 10 to 14 days; more often steroids are given intravenously through a small catheter in the arm. Unless the neurological impairment causes immobility or other severe symptoms that require hospitalization, steroids are usually given at an infusion center for three to five days in a row.
While being treated with steroids, patients should take over-the-counter medication for stomach protection, maintain appropriate hydration and reduce their intake of sweets, as steroids can increase blood sugar levels. Dramatic changes in mood and sleep difficulties may also occur.
Disease modifying treatment in MS is a long-term treatment strategy aiming at prevention of further clinical neurological events or formation of new brain lesions visible on MRI. While there is no cure for MS yet, we are able to control the disease with significant success.
All treatment agents used for this strategy are preventative medications only and cannot affect any prior symptoms present before the treatment starts. It is therefore important to start treatment early, before major neurological impairments start.
Currently, we have multiple medications to choose from, many of them relatively new, that vary in the frequency administered and the method by which they are taken:
Injectable Agents: Interferons and Glatiramer Acetate
Injectable medications have been available on the market for more than 20 years. Two categories are interferons and glatiramer acetate. Both of these medications work by shifting the immune profile from attacking toward protecting the nervous system, but this shift does not make patients prone to common infections.
Interferons vary in how often and the method by which they are injected. Ranging from one injection every two weeks to an injection every other day, interferons are injected under the skin or into the muscle. Automated injectors are usually used, and patients are trained by nurses or nurse practitioners.
Side effects caused by interferons are usually mild and include flu-like symptoms (slight fever, muscle aches, headache and shakes) occurring a few hours after the injection. These symptoms respond to treatment with acetaminophen or ibuprofen.
Other possible side effects include skin changes, mood changes (possible risk of depression) and changes in liver function. While treated with interferons, liver function and blood-cell count must be monitored every three months.
Glatiramer acetate is injected under the skin three times a week. This medication has a very low risk of side effects, but it can cause more pronounced pain or skin changes at the injection site. No blood tests are usually required while using glatiramer acetate.
Intravenous Agents: Natalizumab and Alemtuzumab
Natalizumab is given as an infusion once in 28 days in a specialized infusion center. It is generally a well-tolerated medication without any significant side effects, but it requires an initial test for the presence of a benign virus called JC virus. This virus is found in about 70 to 90 percent of the global population and doesn’t cause any health problems in most people.
Treatment with natalizumab can increase the risk of the virus reactivation and onset of brain infection called PML. Before considering natalizumab treatment, patients are evaluated with a simple blood test looking for the JC virus. Patients testing negative for the virus might be candidates for this treatment option. If the treatment with natalizumab is started, the JC virus testing is repeated every six months to ensure that the patient remains negative. Additionally, liver function tests and blood counts are tested every three months.
Alemtuzumab is the newest medication used in MS. Also administered as an infusion, it is given as two cycles — the first one for five days in a row and the second a year later for three days. Alemtuzumab works by temporarily destroying B cells, a certain type of immune cells responsible for changes in MS. The new B cells that are produced afterward should be less aggressive and not prone to attack the nervous system.
Side effects caused by alemtuzumab can be either immediate infusion reactions or delayed side effects related to the way alemtuzumab works in the body. Immediate infusion reactions include headaches, rash, fevers and nausea. Steroids given with the infusion do successfully decrease these symptoms.
Delayed side effects consist of thyroid gland dysfunction, kidney dysfunction and the destruction of platelets, blood cells needed for blood clotting. Patients treated with this alemtuzumab will need monitoring of kidney and thyroid function as well as blood counts for four years after the last infusion.
Alemtuzumab therapy is currently recommended only for patients with aggressive disease who did not respond to two previously used medications for multiple sclerosis.
Oral Agents: Fingolimod, Teriflunomide and Dimethyl Fumarate (BG-12)
Fingolimod is the first oral medication for MS and used since 2009. It is taken once a day every day and is well tolerated by most patients without major side effects. This medication works by trapping some immune cells (lymphocytes) in lymph nodes (the usual place where immune cells reside) and thus prevents them from traveling into the brain and causing MS attacks. While only certain immune cells are trapped, the overall risk for general infections doesn’t increase.
While there are no major side effects once medication begins, there are a few conditions that have to be checked for before fingolimod is started. In some patients, a decrease in heart rate and blood pressure can happen right after the first pill is taken.
Patients planning to start fingolimod will need ECG and blood pressure check. Fingolimod is not permitted for patients with certain heart conditions. Since the change in the heartbeat usually happens shortly after the first pill is taken, patients are monitored for six hours on the day treatment starts. This monitoring is done in clinics specifically equipped and attended by the proper staff to handle any complications.
An eye exam before the treatment starts and then one every three to six months for the first year is also needed. Liver function tests and blood counts are also monitored every three months.
Teriflunomide has been used for MS since 2012. Taken once a day, it works by decreasing production of certain immune cells responsible for MS attacks. Chemically, teriflunomide is related to leflunomide, a medication that has been used to treat rheumatoid arthritis.
Main side effects caused by this agent are abdominal pain, nausea and possibility of worsening liver function. Other possible side effects include reactivation of chronic tuberculosis, slight hair thinning for the first 30 days and diarrhea and vomiting. Teriflunomide persists in the body even after stopping the medication, and this can last up to two years.
In certain situations teriflunomide has to be removed using a simple procedure called an elimination procedure. Using another medication called cholestyramine (traditionally used to treat high cholesterol) for 11 days, residual teriflunomide is bound and eliminated. With the exception of the unpleasant taste, cholestyramine poses no additional risks to patients. During the teriflunomide treatment liver function tests are checked monthly for the first six months and then every three months; blood counts are also checked every three months.
Dimethyl fumarate (BG-12) is the newest oral medication available to MS patients. Similarly to teriflunomide, it is also chemically related to another medication that has been used in Germany for treating psoriasis. BG-12 is taken twice a day and is thought to be effective against inflammation, a key process in MS.
Two main side effects observed during clinical studies are digestive tract-related side effects and skin flushing. Digestive tract side effects include stomach pain, nausea, vomiting, bloating and possibly diarrhea.
Skin flushing is an uncomfortable but not dangerous side effect causing short-lived redness of the skin and possibly an itching sensation. Taking BG-12 with food significantly decreases the risk for both of these side effects. On rare occasions, BG-12 can also cause a significant to moderate decrease in lymphocyte count. Usual monitoring includes complete blood count and liver function tests every three months.
Two of the oral agents, fingolimod and BG-12, were recently linked with a few cases of progressive multifocal leukoencephalopathy (PML) infection. While a decreased number of lymphocytes for long periods of time seems to be the common denominator in BG-12 cases, the situation is not that straightforward in fingolimod cases because this medication will decrease the number of lymphocytes in all patients.
Still considered a rare event for both of these medications, how this fact will change treatment strategy for MS patients is still not decided by European nor U.S. regulatory agencies. Frequent checks of lymphocyte counts (every three instead of six months) are now considered as well as changes in BG-12 treatment, should the low count persist for longer than six months.
- Oral versus intravenous steroids for treatment of relapses in multiple sclerosis
- Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis
- Disease-modifying therapy for multiple sclerosis
- Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab
- Biogen Reports Another Tecfidera PML Case
- Will 4th PML Case Change Tecfidera Risk Profile?