Multiple Sclerosis (cont.)
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
In this Article
- Multiple sclerosis facts
- What is multiple sclerosis?
- What causes multiple sclerosis?
- Is multiple sclerosis inherited?
- What are the types of multiple sclerosis?
- What are the symptoms of multiple sclerosis?
- How is multiple sclerosis diagnosed?
- What are the treatments for multiple sclerosis?
- Interferons for relapsing multiple sclerosis
- Other medications approved for relapsing multiple sclerosis
- How are the physical manifestations of multiple sclerosis treated?
- What are the future directions for managing multiple sclerosis?
- Multiple Sclerosis (MS) FAQs
- Find a local Neurologist in your town
How is multiple sclerosis diagnosed?
Due to the broad range and subtleties of symptoms, multiple sclerosis may not be diagnosed for months to years after the onset of symptoms. Physicians, particularly neurologists, take detailed histories and perform complete physical and neurological examinations.
- MRI (magnetic resonance imaging) scans with intravenous gadolinium help to identify, describe, and in some instances date lesions in the brain (plaques).
- An electrophysiological test, evoked potentials, examines the impulses traveling through the nerves to determine if the impulses are moving normally or too slowly.
- Finally, examining the cerebrospinal fluid that surrounds the brain and spinal cord may identify abnormal chemicals (antibodies) or cells that suggest the presence of multiple sclerosis.
Collectively, these three tests help the physician to confirm the diagnosis of multiple sclerosis. For a definite diagnosis of multiple sclerosis, dissemination in time (at least two separate symptomatic events or changes on MRI over time) and in anatomical space (at least two separate locations within the central nervous system, which can be demonstrated by MRI or neurological exam) must be demonstrated.
What are the treatments for multiple sclerosis?
There are many issues for the patient and physician to consider in treating multiple sclerosis. Goals may include:
- improving the speed of recovery from attacks (treatment with steroid drugs);
- reducing the number of attacks or the number of MRI lesions; or
- attempting to slow progression of the disability (treatment with disease modifying drugs or DMDs); and
- relief from complications due to the loss of function of affected organs (treatment with drugs aimed at specific symptoms).
Most neurologists will consider treatment with DMDs once the diagnosis of relapsing-remitting multiple sclerosis is established. Many will begin treatment at the time of the first attack of MS since clinical trials have suggested that patients in whom treatment is delayed may not benefit as much as patients who are treated early.
It is important for patients to talk to their doctor before deciding to go on therapy since DMDs differ in their uses (for example, one DMD may be used for slowing progressing disability but not for treatment of the first attack of MS; another DMD may be used for reducing relapses but not for slowing progressing disability). Finally, utilizing support groups or counseling may be helpful for patients and their families whose lives may be affected directly by multiple sclerosis.
Once goals have been set and a decision regarding DMDs has been made, initial therapy may include medications to manage attacks, symptoms, or both. An understanding of the potential side effects of drugs is critical for the patient because sometimes side effects alone deter patients from drug therapy. Patients may choose to avoid drugs altogether or choose an alternative drug that may offer relief with fewer side effects. A continuous dialogue between the patient and physician about the medications is important in determining the needs for treatment.
Although the efficacy of DMDs has been proven in clinical trials, their ability to decrease the frequency of relapses varies in patients with relapsing MS. It is difficult to clearly delineate these differences in the absence of comparative clinical trials, and physicians should consider this limitation in interpreting the reported relapse reduction rates from individual placebo-controlled trials. It is not acceptable to compare data across trials; however, the following relapse reduction rates vs. placebo for some of the DMDs from the pivotal trials are provided for general information purposes:
- Avonex: 18% (annual relapse rate reduction)
- Copaxone: 29% at 2 years
- Rebif: 32% at 2 years
- Betaseron and Extavia: 31% (annual relapse rate reduction)
- Tysabri: 68% (annual relapse rate reduction)
- Gilenya: 54% (annual relapse rate reduction)
- Teriflunomide: 31% (annual relapse rate reduction)
In head-to-head trials in patients with relapsing MS, both Rebif and Gilenya have shown superiority to Avonex in reducing relapse rates and MRI lesions (EVIDENCE and TRANSFORMS trials, respectively).
Drugs known to affect the immune system have become the primary focus for managing multiple sclerosis. Initially, corticosteroids, such as prednisone (Deltasone, Liquid Pred, Deltasone, Orasone, Prednicen-M) or methylprednisolone (Medrol, Depo-Medrol), were widely used. However, since their effect on the immune system is nonspecific (general) and their use may cause numerous side effects, corticosteroids now tend to be used to manage only severe multiple sclerosis attacks (that is, attacks leading to physical disability or causing pain).
Interferons for relapsing multiple sclerosis
Since 1993, medications that alter the immune system, particularly interferons, have been used to manage multiple sclerosis. Interferons are protein messengers that cells of the immune system manufacture and use to communicate with one another. There are different types of interferons, such as alpha, beta, and gamma. All interferons have the ability to regulate the immune system and play an important role in protecting against intruders including viruses. Each interferon functions differently, but the functions overlap. The beta-interferons have been found useful as DMDs in managing multiple sclerosis.
Overall, patients treated with interferons experience fewer relapses or a longer interval between relapses. Avonex and Rebif are used to slow progressing disability. The most common side effect is a flu-like syndrome that includes fever, tiredness, weakness, chills, and muscle aches. This syndrome tends to occur less frequently as therapy continues. Other common side effects are injection site reactions, changes in blood cell counts, and abnormalities of liver tests. Regular liver tests and blood counts are recommended for patients receiving beta-interferons. Periodic thyroid function testing also is recommended because of the effects of beta-interferons on the thyroid gland. With the concomitant use of analgesics and evolving nursing experience with managing local skin reactions, the tolerability to interferons seems to have improved over the years.
Clinical trials of beta-interferon in patients with the first attack of multiple sclerosis showed that in this early patient population, the second attack was delayed. Interferons approved by the FDA for treatment at the first attack of multiple sclerosis include Avonex, which is administered intramuscularly once a week, and Betaseron or Extavia, which are administered subcutaneously every other day.
Available beta-interferons include:
Interferon beta-1b (Betaseron and Extavia) are used for the treatment of relapsing forms of multiple sclerosis, to reduce the frequency of clinical relapses. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Betaseron and Extavia received approval for use by the FDA in 1993 and 2009, respectively. Both are injected subcutaneously (below the skin).
Interferon beta-1a (Rebif) is used for the treatment of patients with relapsing forms of multiple sclerosis to decrease the frequency of clinical relapses and delay the accumulation of physical disability. Efficacy of Rebif in chronic progressive multiple sclerosis has not been established. Rebif received approval for use by the FDA in 2002 and is injected subcutaneously.
Interferon beta-1a (Avonex) is used for the treatment of patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical relapses. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Safety and efficacy in patients with progressive multiple sclerosis has not been established. Avonex received approval for use by the FDA in 1996 and is injected intramuscularly (into the muscle).
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