Multiple Sclerosis Medications

Multiple sclerosis (MS) can be thought of as an inflammatory process involving different areas of the central nervous system (CNS) at various points in time.

The cause of multiple sclerosis is not known. Both environmental and genetic factors are thought to predispose a person to develop the disease.

Multiple sclerosis results in the destruction of the myelin that surrounds the nerves of the CNS. Myelin is a fatty substance that insulates the nerves and allows them to transmit information to and from the brain. If the myelin is damaged, the transmitted information is not only delayed but also may be misinterpreted by the brain. The myelin destruction, also known as demyelination, is thought to be caused by the body's immune cells entering the CNS. The disruption of the normal barrier to the entry of these cells, termed the blood-brain barrier, leads to local swelling (known as edema). Also damaged are the nerve cell bodies (termed neuronal loss) or their prolongations (termed axonal loss). A plaque (area of inflammation, demyelination, axonal loss, edema or scarring) represents a typical multiple sclerosis lesion, or area of injury.

What initially triggers the immune system attack is not known. Microglia are cells in the CNS that take up fragments of myelin and present these fragments to the immune cells. In healthy individuals, this presentation of myelin fragments is not thought to trigger the immune cells to attack the CNS. In people with multiple sclerosis, this presentation of myelin fragments may trigger an exaggerated response by immune cells that leads to the formation of plaques around the blood vessels in the CNS.

Perhaps the most common symptom of MS is sensory disturbance, which manifests as tingling or numbness sensations, throughout the body.

Visual disturbances are also among the most common symptoms and:

• Blurred or hazy vision
• Color perception alteration

Vision loss may occur because of the development of optic neuritis (inflammation of the optic nerve). In a typical case of optic neuritis, the person with multiple sclerosis experiences ocular pain with eye movement.

Other common symptoms include:

• Loss of balance and fine motor skills
• Facial pain or weakness
• Vertigo (a spinning sensation)
• Limb weakness or paralysis
• Impaired control of bladder or bowel function
• Fatigue
• Depression
• Memory loss

Individuals with advanced disease lose the ability to walk and may become bedridden, requiring assistance with most activities.

No, currently there is no vaccine or treatment cure for multiple sclerosis.

Several medications are now available to decrease the number of attacks (periods of relapse) of multiple sclerosis or delay the progression of physical disability. Your doctor or health care professional my prescribe medications and other therapies to treat general symptoms associated with the disease, such as depression, muscle spasms, fatigue, bladder problems, tremors (shakiness), poor coordination, and sexual dysfunction.

Interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaseron), and glatiramer acetate (Copaxone), are examples of immune-modifying drugs used for MS.

Generally, these medications tend to decrease the frequency of attacks in patients with mild-to-moderate relapsing remitting MS (RRMS) by 18% to 33%. The rate of new lesions that appear on magnetic resonance imaging (MRI) is also reduced by approximately one-third. With the interferon drugs, the effectiveness is directly related to the dose (higher doses of IFN, if tolerated, are generally more effective). Whether the delay in the onset of new attacks by these drugs ultimately has a long-term impact on the disability associated with multiple sclerosis is controversial. However, clinical trials suggest that patients receiving early treatment have a beneficial impact on relapses and disability that may not be matched by patients in whom the treatment is delayed. Research regarding this continues.

The ability to respond to long-term interferon beta-1a and beta-1b may be limited, in some patients, by the development of persistent, high titer neutralizing antibodies. Patients treated with glatiramer also eventually develop antibodies, but these antibodies do not seem to limit glatiramer's activity.

Methylprednisolone (Solu-Medrol) is the corticosteroid most frequently used intravenously to speed up the recovery from MS attacks. It is most helpful if administered shortly (within a few days) after the onset of the attack.

• How corticosteroids work: Corticosteroids affect immunologic actions, such as inflammation (swelling) and immune responses associated with an acute (sudden) attack of multiple sclerosis. Corticosteroids are used for short periods to reduce the duration and severity of symptoms associated with a sudden attack.
• Who should not use these medications:
  • Individuals allergic to corticosteroids
  • Individuals with active peptic ulcer disease
  • Individuals with systemic fungal infections
• Who should use caution in using these medications:
  • People with diabetes, seizures, hypertension, congestive heart failure, osteoporosis, tuberculosis or viral infections, or impaired liver function
  • People taking other medications (These people should consult their doctor because levels of some medications may be elevated when used along with corticosteroids.)
• Use: Solu-Medrol is administered intravenously (IV) for 3-5 days to treat a sudden multiple sclerosis attack. Steroids do not have an impact on the degree of clinical recovery, but rather in shortening the timing to recovery.
• Drug or food interactions: Many drug interactions are possible. Contact a doctor or pharmacist before taking a new prescription or over-the-counter medications. Aspirin; nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil) or naproxen (Aleve); or other medications associated with stomach ulcers may increase the risk of developing stomach ulcers. Corticosteroids may decrease potassium levels; therefore, caution must be used when taking other medications that decrease potassium levels, such as diuretics, for example, furosemide (Lasix).
• Side effects: Ideally, corticosteroids are used for short periods in order to control sudden flares in multiple sclerosis symptoms. Short-term use may cause fluid retention, potassium loss, stomach distress, weight gain, and changes in emotion. Long-term use is associated with serious side effects such as osteoporosis (calcium and vitamin D supplementation is advised), adrenal insufficiency, psychosis, immunosuppression, peptic ulcer, hypertension, insomnia, menstrual irregularities, acne, skin atrophy, elevated blood sugar, abnormal appearance of the face (Cushingoid face), increased risk of infection, and cataracts.
  • Induction of problems with blood sugar levels and worsening of diabetes control: Changes in diet or initiating oral antidiabetic medications or insulin may be required. For individuals who already have diabetes, dosage changes may be needed for the insulin or the antidiabetic medications.
  • Weight gain: This is a common problem with high-dose corticosteroids due to fluid retention and endocrine alterations. Salt restriction is advised, and with a doctor's approval, potassium supplementation may be needed. A doctor may prescribe a diuretic (water pill) to increase urination to eliminate some of the excess fluid.

Mitoxantrone (Novantrone) is a Food and Drug Administration (FDA) approved immunosuppressant used for treatment of multiple sclerosis. Other immunosuppressants, such as cyclophosphamide (Cytoxan), azathioprine (Imuran), or methotrexate (Rheumatrex, Trexall), are prescribed primarily in specialized centers; but their efficacy in multiple sclerosis remains controversial and they are not FDA approved for this use. These drugs should not substitute for the immune-modulating drugs as first-line agents in newly diagnosed relapsing remitting multiple sclerosis (RRMS). Some physicians find a role for Cytoxan, Imuran, and methotrexate as last-resort measures for patients who have not responded to the FDA approved drugs or that have a fulminant (malignant) course of multiple sclerosis that may be life threatening.

How immunosuppressants work: This group includes a wide variety of agents that work in many different ways, but they all interfere in the immune-system processes that cause inflammation.

• Who should not use these medications:
  • Individuals allergic to any of these medications
  • Women who are pregnant or breastfeeding
  • Individuals with preexisting bone marrow suppression
  • Individuals with diseases causing low blood count
• Dosing: Depending on the drug prescribed, immunosuppressants may be administered orally or intravenously.
• Drug or food interactions: The use of immunosuppressants increases the risk of infection, increases toxicity to bone marrow or blood cells, and may lead to cancer. Many drug interactions are possible. Contact a doctor or pharmacist before beginning a new prescription or over-the-counter medication.
• Side effects: Immunosuppressants are not safe during pregnancy, may cause bone marrow or blood cell toxicity, or may lead to cancer. Patients with impaired kidney or liver function may need lower doses and close monitoring. Methotrexate may cause toxicity of the liver or lungs (fibrosis or pneumonitis) and even damage to the nervous system (leukoencephalopathy or myelopathy). Mitoxantrone may cause heart problems and requires monitoring with echocardiograms (ultrasonography of the heart) before and during therapy. Cyclophosphamide may cause bleeding within the bladder and even bladder cancer. Follow the doctor's recommendations on fluid intake while taking these medications.
• Indications for Immunosuppressant Drugs in multiple sclerosis

Mitoxantrone (Novantrone): indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Novantrone is not indicated in the treatment of patients with primary progressive multiple sclerosis.

Fingolimod (Gilenya): Fingolimod (Gilenya) is a daily oral medication to treat MS that was approved by the US FDA in September 2010 as the first oral medication to treat MS. Although the exact mechanism of action of fingolimod is unclear, it appears to work by reducing the number of lymphocytes (a type of white blood cell that is important for immunity and the inflammation process) in the blood. Fingolimod is taken daily in capsule form. It is not a cure for MS, but it has been shown to decrease the number of MS flares and slow down the development of physical disability caused by MS. Like many injectable therapies for MS, the long-term safety of fingolimod is unknown. The most common side effects of fingolimod are headache, flu, diarrhea, back pain, elevations of liver enzymes in the blood, and cough. Other side effects are also possible including eye problems, so those taking this drug should have regular ophthalmologic evaluations.

Plasmapheresis (plasma exchange): This therapy is sometimes attempted for treatment of severe attacks of the disease that do not respond to corticosteroids. This therapy is expensive, not FDA approved for multiple sclerosis, and its efficacy is controversial.

IV immune globulin (IVIG): Although not FDA approved for multiple sclerosis, some studies have suggested that IVIG can reduce the rate of a second attack when IVIG was administered over 6 weeks following a first attack. Other researchers found no benefit when given to patients who had the condition for at least 3 years. Yet others have studied IVIG when given on a regular monthly schedule and found a small but significant benefit of improving clinical disabilities and fewer relapses.

Cladribine (Mavenclad) is a drug used to treat two forms of multiple sclerosis; relapsing forms that include relapsing-remitting disease and active secondary progressive disease in adults. Generally, cladribine is used in people with MS who have tried other multiple sclerosis medications that were not tolerated well or ineffective. People with clinically isolated syndrome not take cladribine.

Research into additional treatment options continues to advance. Multiple approaches are being investigated based on the increasing knowledge about immune system abnormalities and CNS lesion formation in multiple sclerosis. These include approaches to counteract or reduce immune system activation, blood brain barrier disruption, neuronal loss, and myelin loss, among other investigational efforts.