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Promising New Treatments for Multiple Sclerosis

Multiple sclerosis is a lifelong disease that requires various modalities of treatment. Plan of care considerations include (1) the patient’s age at onset of illness; (2) sex; (3) the extent of the disability at the time of diagnosis as well as (4) the form of multiple sclerosis. Treatment will be a multidisciplinary approach that involves specialists such as neurologists, rehabilitation specialists, neuro-urology experts, psychiatrists, occupational therapists, physiotherapists and social workers.

Promising New Treatments for Multiple Sclerosis
This method is essential to ensure that all aspects of the disease are considered to help improve their quality of life.

The management of multiple sclerosis consists of a four-prong approach that involves: (1) management of acute exacerbations; (2) reduction of the frequency of relapses; (3) administration of the complications and (4) management of permanent disability that has already occurred.  These are the goals of the management. No cure for the disease has been established.

Management of Acute Exacerbations (index demyelinating episodes)

High-dose steroids such as corticosteroids are the cornerstone of treating acute exacerbations because they reduce and control inflammation. Steroids are generally reserved for patients with exacerbations severe enough to cause functional disability or in those that exacerbations are prolonged beyond the duration of 24 hours. Corticosteroids work by reducing the inflammation which is a primary cause of the systems of multiple sclerosis. They work by binding to receptors on the cell surface and preventing the formation of various proteins. This, in turn, leads to inflammatory activity suppression. 2014 guidelines recommend pulsing with intravenous methylprednisone or methylprednisone given orally at doses of 500mg to a maximum of 1 g and 2 g respectively for a total of 3-5 days. The steroids can then be tapered off over two weeks or, be followed by a dose of prednisone 60-80 mg once a day which can be tapered off over two weeks.

Pulsing with high-dose steroids helps to reduce the severity of the acute attack as well as reduce the number of days of disability. However, their benefit in preventing future relapses or halting disease progression has not been shown. Their use is limited to a maximum of three times a year due to the multiple adverse effects that result from chronic steroid use. These include: osteoporosis, psychosis, mood lability, cataracts, gastritis, fluid retention, weight gain, Cushing’s syndrome, increased insulin resistance and increased the incidence of infections. Proton pump inhibitors such as esomeprazole have been used for prevention of gastritis especially in patients who report the incidence of peptic ulceration. Histamine receptor antagonists have also been used. Lithium, a mood stabilizer, has been used in the management of the mood disorders that result.

Plasmapheresis has also been used in the management of acute episodes where corticosteroids fail. Its wide use is limited by resources as it is quite expensive.

Reduction of frequency of relapses

The relapsing-remitting form of multiple sclerosis is characterized by episodes of attacks followed by periods of disease remission. One of the goals of treating these patients is to prevent the relapses. Disease modifying drugs are used to achieve this. The two main drugs used are Glatiramer acetate and Interferon beta (IFN β). These two drugs should be initiated before permanent disability sets in because they have no effect on permanent neurological deficits. Four conditions need to be met before therapy with these agents can be started. They are: (1) the patient should be physically fit and able to walk for a substantial distance without assistance; (2) they should have a history of at least two severe relapses in the past 24 months; (3) they should be above 18 years and (4) they should have no contraindications to the use of the two drugs.

Interferon β belongs to a group of cytokines in the body called interferons. It is classified under Class 1 of that group. The two forms of interferon β have been found to be useful in the management of relapsing/remitting multiple sclerosis are as follows: interferon β 1a (Avonex and Rebif) and interferon β 1 b (Betaferon). The mechanism of action of these drugs involves reducing the frequency and severity of attacks by (1) lessen the manifestation of Major Histocompatibility Complexes (MHC) on the surface of antigen presenting cells; (2) inhibiting cytokines that favor inflammation and increasing those that regulate the levels of other cytokines; (3) reducing T-cell proliferation and (4) lessen the entry of inflammatory cells into the central nervous system.

Avonex is given as an intramuscular injection, 30 micrograms once per week. Rebif is given subcutaneously, 44 micrograms three times a week. Betaferon is also given subcutaneously, 250 micrograms every other day. Some of the common side effects of interferon therapy include skin reactions at the sites of injection causing necrosis; lipoatrophy due to the subcutaneous injections and flu-like symptoms like headaches, fever, fatigue and muscle aches.

Glatiramer acetate is an immunomodulatory drug that contains four amino acids: glutamic acid, lysine, alanine, and tyrosine. It has been shown to reduce the frequency of attacks in patients with relapsing- remitting form. The mechanism of action is not well elucidated, but various theories exist. Some of these theories suggest that glatiramer can facilitate the conversion of inflammatory T cells into non-inflammatory forms as well as act as a decoy since it has a similar structure to the myelin which is the target of the inflammation. It has however not been shown to influence the permeability of the blood-brain barrier as the interferons do. Glatiramer is given as a subcutaneous injection, 20 mg daily. Just like Interferon β, it causes injection site reactions.

Other drugs that have been used in the prevention of attack rate include Natalizumab, Fingolimod, Teriflunomide, Mitoxantrone Hydrochloride, Cladribine, Intravenous Immunoglobulins, Methotrexate, and Cyclophosphamide.

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