Information ⬇
- Ten treatments are available in the United States: interferon (IFN)-β1a (Avonex; 30 µg IM once a week), IFN-β1a (Rebif; 44 µg SC thrice weekly), IFN-β1b (Betaseron; 250 µg SC every other day or Extavia; 0.25 mg SC every other day), glatiramer acetate (Copaxone; 12 mg/d SC), natalizumab (Tysabri; 300 mg IV every 4 weeks), fingolimod (Gilenya; 0.5 mg PO daily), dimethyl fumarate (Tecfidera; 240 mg PO twice daily after initial lower starting dose), teriflunomide (Aubagio; 7-14 mg PO daily), mitoxantrone (Novantrone; 12 mg/m2 IV every 3 months), and alemtuzumab (Lemtrada; 12 mg IV daily for 5 days followed 12 months later with 12 mg IV daily for 5 days) (see Fig. 190-2).
- IFN preparations that are given multiple times weekly (e.g., Rebif or Betaseron/Extavia) appear to have slightly greater efficacy compared with once-weekly agents (e.g., Avonex).
- Side effects of IFN include flulike symptoms, injection-site reactions (with SC dosing), and mild abnormalities on laboratory evaluation (e.g., elevated liver function tests or lymphopenia). Rarely, severe hepatotoxicity may occur. Side effects of IFN often subside with time. Injection-site reactions also occur with glatiramer acetate but are less severe than with IFN. Approximately 15% of pts receiving glatiramer acetate experience one or more episodes of flushing, chest tightness, dyspnea, palpitations, and anxiety.
- Fingolimod is generally well tolerated, and oral dosing is convenient for pts. First-degree heart block and bradycardia can occur, necessitating the prolonged (6-h) observation of pts receiving their first dose.
- Dimethyl fumarate has a twice-daily oral dosing schedule that makes it somewhat less convenient for pts. GI side effects are common as treatment is initiated, but usually subside with continued administration.
- Teriflunomide is well-tolerated and convenient for pts given its once daily oral dosing. However, there is less evidence of its superiority to the injectable medications than for the other oral agents A major limitation in women of childbearing age is its possible teratogenicity.
- Natalizumab is the most effective MS agent available; however, because of the development of progressive multifocal leukoencephalopathy (PML) in 0.3% of pts, it is generally used only for pts who have failed other therapies or who have particularly aggressive presentations. A blood test to detect antibodies against the PML (JC) virus can identify individuals who are at highest risk for this complication.
- Most pts with relapsing MS and a mild initial course receive an injectable (IFN-β or glatiramer acetate) or oral (dimethyl fumarate, fingolimod, or teriflunomide) agent as first-line therapy.
- For pts presenting with a moderate or severe initial course, either an oral agent (dimethyl fumarate or fingolimod) or, if the pt is JC virus antibody seronegative, infusion therapy with natalizumab is recommended.
- Regardless of which agent is chosen first, treatment should probably be altered in pts who continue to have frequent attacks (Fig. 190-2).
- Several studies suggest that these agents can improve the long-term outcome of MS. Thus, early treatment with a disease-modifying drug is appropriate for most pts. It may be reasonable to delay initiating treatment in pts with (1) a normal neurologic examination, (2) a single attack or a low attack frequency, and (3) a low burden of disease as assessed by brain MRI.
- Untreated pts need to be followed closely; the need for therapy is reassessed if there is evidence of ongoing disease.
- Vitamin D deficiency should be corrected in all pts with MS, usually by oral supplementation with vitamin D3, 4000-5000 IU daily.
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