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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Corticosteroids

Corticosteroids were the first and most commonly used immunosuppressant medications in MG. Prednisone is generally used when symptoms of MG are not adequately controlled by cholinesterase inhibitors alone. Good response can be achieved with initial high doses which are then tapered to the lowest dose to maintain the response. Temporary exacerbation can occur after starting high doses of prednisone within the first 7-10 days and can last for several days [35, 36]. In mild cases, cholinesterase inhibitors are usually used to manage this worsening. In cases of severe exacerbation, PE or IVIg can be given before or with corticosteroid therapy to prevent or reduce the severity of corticosteroid-induced weakness and to induce a more rapid response. Oral prednisone might be more effective than anticholinesterase drugs in oMG and should therefore at least be considered in all patients with oMG [37, 38].

Nonsteroidal Immunosuppressive Agents

Azathioprine, a purine analog, reduces nucleic acid synthesis, thereby interfering with T- and B-cell proliferation. It has been utilized as an immunosuppressant agent in MG since the 1970s and is effective in 70-90% of patients with MG [45]. It usually takes up to 15 months to detect clinical response. When used in combination with prednisone, it might be more effective and better tolerated than prednisone alone [49]. Adverse side effects include hepatotoxicity and leukopenia [50]. The patients being considered for treatment with azathioprine should be screened for thiopurine methyltransferase (TPMT) deficiency either by plasma levels or genetic testing. Those people who have low levels of TPMT are at higher risk of adverse effects from azathioprine and should not receive the drug.

Mycophenolate mofetil selectively blocks purine synthesis, thereby suppressing both T-cell and B-cell proliferation. Widely used in the treatment of MG, its efficacy in MG was actually suggested by a few nonrandomized clinical trials [31, 32].

The standard dose used in MG is 1000 mg twice daily, but doses up to 3000 mg daily can be used. Higher doses are associated with myelosuppression, and complete blood counts should be monitored at least once monthly. The drug is contraindicated in pregnancy and should be used with caution in renal diseases, GI diseases, bone marrow suppression, and elderly patients [33].

Cyclophosphamide administered intravenously and orally is an effective treatment for MG [34]. More than half of the patients become asymptomatic within

1 year of treatment. Undesirable side effects include hair loss, nausea, vomiting, anorexia, and skin discoloration, which limit its use to the management of patients who do not respond to other immunosuppressive treatments [2].

Cyclosporine blocks the synthesis of IL-2 cytokine receptors and other proteins critical to the function of CD4+ T cells. Cyclosporine is used mainly in patients who do not tolerate or respond to azathioprine. Large retrospective studies have supported its use as a steroid-sparing agent [45].

Tacrolimus has been used successfully to treat MG at low doses. It has the theoretical advantage of less nephrotoxicity than cyclosporine. However, there are more controlled trial data supporting the use of cyclosporine. Like other immunosuppressive agents, tacrolimus also has the potential for severe side effects [2].

MG patients resistant to therapy have been successfully treated with cyclophosphamide in combination with bone marrow transplant or with rituximab, a monoclonal antibody against the B-cell surface marker CD20 [26].

Etanercept, a soluble and a recombinant tumor necrosis factor (TNF) receptor blocker, has also been shown to have steroid-sparing effects in studies on small groups of patients [2, 27].

 
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