Treatment of Multiple Sclerosis

Treatment of multiple sclerosis (MS) is aimed at slowing disease progression and preventing development or worsening of disability. New neurologic symptoms (“relapses”) or progression of disability indicate ongoing disease activity. Further, the presence of new lesions on brain magnetic resonance imaging (MRI) serves as a surrogate of disease activity even in the absence of new symptoms, and thus has implications for modifying treatment. Medications ( Table 112.1 ) used to treat MS primarily target the adaptive immune response system. When considering which treatment to use, it is important to assess (1) the degree of disease activity, (2) the side effect and risk profile of specific therapies, (3) patient preferences in terms of route of administration or risk/benefit profile, and (4) insurance coverage and financial resources, as MS therapies can be very expensive.

  • A.

    All agents approved to treat MS have shown benefit in the relapsing-remitting form of the disease and are also felt to be useful in secondary progressive MS with evidence of disease activity. In primary progressive MS, however, disability slowly accrues despite the absence of discrete relapses, At present, only ocrelizumab and, in rare cases, mitoxantrone are approved for primary progressive MS. Mitoxantrone use is limited by dose-related cardiac toxicity and requires monitoring with echocardiography.

  • B.

    Steroids (methylprednisolone, 1 g/day × 3–5 days, given intravenously) may hasten recovery in the case of clinical relapse, and can be given with or without an oral steroid taper. Typical side effects of steroids may occur and should be considered when weighing the decision to treat. Alternatives (if patient has side effects from steroids or they are deemed ineffective) include adrenocorticotropic hormone (dosed intravenously) or plasma exchange; both of these are more expensive and are used sparingly.

  • C.

    Disease activity can be broadly divided into (1) mild disease, in which the clinician interprets radiographic and/or clinical burden along with concern for future disease to be lower; (2) moderate disease, in which there is greater concern about future disease course or accumulation of disease activity; and (3) markedly active disease, in which there is neurologic or radiographic worsening or demonstration of significant burden of disease in the recent past. With more severe disease, more aggressive immunomodulating therapies are warranted despite an increased risk of serious side effects with these agents.

  • D.

    β-Interferons and glatiramer acetate are given via subcutaneous injection. They have excellent safety profiles and, among approved MS therapies, have been in use the longest. They have often been termed platform therapies for these reasons. Liver function tests (LFTs) should be checked every 3–6 months in patients on interferons; no monitoring is required with glatiramer acetate. Teriflunomide and dimethyl fumarate are both oral medications and are preferred by some patients for this reason. These have similar or slightly better efficacy than the interferons or glatiramer acetate, but do carry some risks (specifically pregnancy concerns with teriflunomide, gastrointestinal upset, flushing, and rare infections with dimethyl fumarate). Teriflunomide requires frequent monitoring of LFTs, a screen for tuberculosis prior to starting therapy, and contraceptive counseling, as pregnancy must be avoided due to potential teratogenicity. Blood count monitoring for lymphopenia must be done every 3–6 months with dimethyl fumarate.

  • E.

    In moderate disease, the oral agent fingolimod is effective, but cardiac monitoring must be performed with the initial dose due to the occurrence of bradycardia in some patients. Varicella immunization and screening every 3–6 months for lymphopenia and macular edema must also be performed. Ocrelizumab is a potent antiinflammatory given intravenously at 6-month intervals. Premedication with acetaminophen, methylprednisolone, and antihistamines is required to decrease the not infrequent occurrence of infusion reactions, and pretreatment screening for hepatitis should be performed. Natalizumab, dosed intravenously at monthly intervals, is one of the most potent agents for MS but carries a small risk of progressive multifocal leukoencephalopathy (PML), which is caused by the JC virus. Testing for JC virus antibody may help stratify risk, as antibody-negative patients appear to be at lower risk of PML than those with positive antibodies. When used long term, antibody status should be assessed two to three times per year along with surveillance MRI to evaluate for PML.

  • F.

    In cases of marked disease activity (typically despite use of less potent agents), natalizumab may be considered and a greater risk for PML may be tolerated, or alemtuzumab may be used. Alemtuzumab, which is given once yearly, appears to have efficacy even when used in a discontinuous fashion, i.e., some treated patients may not need to continue it beyond the first or second yearly dose. Unfortunately, it not infrequently leads to other medical issues (thyroid disease develops in one-third of patients subsequent to treatment), and close monitoring for rare but potentially serious complications (e.g., thrombocytopenia and renal disease) is required. Monthly blood count, urinalysis, LFTs, and 3-monthly thyroid function testing are recommended.

  • G.

    Potent immune suppressants and/or chemotherapeutics such as cyclophosphamide and methotrexate have been used off-label in some patients with MS who have not responded to conventional agents.

  • H.

    In the absence of new symptoms, imaging with MRI of the brain (and in select cases spinal cord) should typically be done yearly to assess for disease activity. When present, therapy may need to be modified, and repeat short-term interval imaging is indicated. It may also be helpful to have imaging at start or change of therapy for comparison in the future. Deescalation of therapy (such as moving from a more to less potent agent) can be considered when the concern for disease activity is reduced, such as in a patient with stable imaging for a number of years, older patients, or in those more likely to encounter or more vulnerable to serious side effects.

Algorithm 112.1

May 3, 2021 | Posted by in NEUROLOGY | Comments Off on Treatment of Multiple Sclerosis
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