Long-Term Immunosuppression Therapies

Corticosteroids, Prednisone, Azathioprine, and Cyclosporine are the agents now used for long-term immunosuppression in myasthenia gravis.


CORTICOSTEROIDS:
Corticosteriods are the most commonly used and most consistently affective immunosuppressive agents for the treatment of myasthenia gravis. They have been especially beneficial in patients with moderate to severe myasthenic musclar weakness. They appear to exert suppressive effects at many levels of the immune system. This is possible because corticosteroids may reduce acetylcholine receptor antibody levels and diminish the anti-acetylcholine-receptor antibody reactivity of peripheral-blood lymphocytes. Also, corticosteroids experimentally increase the synthesis of acetylcholine receptors in cultured muscle cells, so it is possible that they could produce more Ach receptors in the body. Corticosteroids may also enhance neuromuscular transmission. Unfortunately, corticosteroids have the largest array of potential side effects. The need for anticholinesterase drugs usually decreases as the patient improves. This therapy is not curative, therefore administration may be required indefinitely or reinstituted periodically when needed.

Patients with moderate-to-severe generalized weakness are hospitalized for the initiation of steroid therapy because of the risk of transient steroid-induced exacerbation of the disease, which may occur during the first weeks of treatment in up to 48 percent of patients. The risk of exacerbation can be minimized by increasing the dose gradually, at a rate guided by the patient's clinical response, with an end point of improvement or 50 to 60 mg per day. Improvement usually begins within 2 to 4 weeks, with maximal benefit realized after 6 to 12 months or more. After about 3 months of daily high-dose treatment, the schedule is gradually modified to an alternate-day regimen to minimize the side effects. The total dose is then tapered very slowly but may require months to years to determine minimal effective dose.

AZATHIOPRINE:
Azathioprine can provide some degree of benefit to more than 90% of patients, and has restored muscle control to a near normal state in some patients. The mechanism by which modulation of the immune response is not completely understood; but it is known that azathioprince suppresses T-cell activity more than B-cell activity.

The therapeutic effect is characteristically delayed with immunosuppressive agents. Also, azathioprine is commonly used in conjunction with thymectomy and coritcosteroids, therefore the effectiveness is hard to evaluate. The clinical benefits may not be observed for three to eight months, and treatment can continue for up to two years after benefits are initially observed. In most patients with severe myasthenia gravis, therapeutic effects and the best results are noted in late-onset, rapidly progressive myasthenia gravis in older patients, or in patients of all age groups with thymoma.

CYCLOSPORINE
Cyclosporine is a potent immunosuppressive agent that inhibits the production of interleukin-2 by helper T cells. It works more quickly than azathioprine, usually within one or two months. Some side effects attributed to cyclosporine include nephrotoxicity and hypertension, which limits use in patients with pre-existing -renal disease or uncontrolled hypertension. Because of these effects, the dose should be guided by monitoring the clinical efficacy or the drug through plasma levels of cyclosporine, and force of the side effects. After a satisfactory clinical response is attained, dose gradually tapers until a minimal required maintenance level is obtained. A big draw back to cyclosporine is its high cost, which limits its availability.