As MG is an autoimmune condition, the mainstay of treatment involves attacking the immune system. The more common immunosuppressive agents are listed in
Table 3. When using any of these agents, careful monitoring of the complete blood cell count (CBC), electrolyte panel, and the liver and renal profiles is essential. The doses may need to be adjusted according to the patient's white blood cell count.
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Steroid Therapy—As a general rule, most patients with MG require steroid therapy at some point during treatment. Steroids may potentially reduce the AchR-Ab titer in patients with MG.
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The typical dosage of prednisone is 1 mg per kilogram of body weight daily, administered as a single oral dose. It is important to start patients on a low dose of prednisone and gradually titrate the dose up. Patients may have transient worsening of MG symptoms during the first 2 to 3 weeks of prednisone therapy. Patients should be warned of these potential adverse effects at the initial stages of therapy and reassured that they will have benefits in 6 to 8 weeks after therapy is initiated.
The drug is usually started at 5 mg daily and may be increased by 5 mg every 4 to 7 days until a clinical benefit is achieved or 1 mg per kilogram of body weight is reached. Once a therapeutic dose is achieved, the patient should remain on this dose for about 2 months. Then a regimen to switch to alternate-day therapy should be instituted. Once the patient's condition is stabilized, the dosage may be slowly tapered downward. In general, the dose should be tapered downward by 5 mg every month. It is not uncommon for patients to relapse after the steroids have been tapered off—another hazard they should be alerted to in advance of a change in dosage. Most patients who have MG generally require long-term low-dose prednisone therapy to maintain remission of symptoms.
Patients should also be informed in advance of other adverse effects not relating to their current symptoms of MG: acne, bruising (occur easily and difficulty in healing), cataracts, imbalances on electrolyte panel test results, hirsutism, hyperglycemia, hypertension, necrosis of the femoral head, obesity, osteoporosis, and steroid-induced myopathy. Patients with type 2 diabetes mellitus who are taking oral agents to control symptoms of MG may require insulin therapy to treat diabetes symptoms during this period. Appropriate precautionary measures should be followed to avoid any of the aforementioned adverse effects.
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Azathioprine—The most commonly used drug to treat patients with MG is now azathioprine.
3 It allows tapering of steroid dosage and reduces some of the adverse effects of steroid therapy. Commonly, the patient will not have clinical benefit from azathioprine for about 4 to 6 months and sometimes longer.
The typical starting dose of azathioprine is 50 mg daily for the first week (test dose), and then the dose is titrated up to a maximum of 2 mg to 3 mg per kilogram of body weight daily in two or three divided doses.
The most common adverse effects are neutropenia and liver function abnormalities. Thus, results from regular CBC counts and liver profile tests should be routinely followed for patients receiving azathioprine therapy.
Rarely, an acute hypersensitive reaction develops when initiating this treatment modality. Therefore, a test dose is commonly used during the first week of treatment. Although the long-term effects of azathioprine are not well known, some concern has been raised about an increased risk of malignancy.
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▪ Cyclosporine—A powerful immunosuppressant that inhibits T-cell activation is cyclosporine. This agent is usually prescribed for patients who have failed to respond to combination therapy with prednisone and azathioprine and those who cannot tolerate azathioprine.
The standard starting dose for cyclosporine is 25 mg twice daily and titrated up to a maximum of approximately 3 mg to 6 mg per kilogram of body weight. However, immunosuppressive therapy should always be tailored to the individual patient; combination therapy is often more efficacious (ie, allowing for reduced dosage and fewer adverse effects) than monotherapy.
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While patients' are receiving this treatment, their blood levels (troughs) of cyclosporine should be checked periodically. The most important adverse effects are nephrotoxicity and hypertension.
▪ Cyclophosphamide—In general, cyclophosphamide is used only when other agents have failed or are not well tolerated by the patient. Cyclophosphamide therapy may be started at 25 mg daily and gradually increased up to a maximum of approximately 2 mg to 5 mg per kilogram of body weight daily.
An increased incidence of hemorrhagic cystitis accompanies the use of this medication in some patients.
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Mycophenolate Mofetil—A novel immunosuppressive agent for treatment of MG that has already been shown to be of benefit in transplantation medicine is mycophenolate mofetil. Recent openlabel trials in patients with MG have shown this medication to provide significant benefit.
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The standard daily dosage for this medication is 1 g to 2 g. Patients may be started at 250 mg of mycophenolate mofetil twice daily, and the dosage can be titrated upward as needed. When starting this agent, the patient's CBC count should be checked every week for the first month of treatment, every 2 weeks for the next 6 to 8 weeks, and monthly thereafter.
Currently, this agent is considered a useful alternative treatment modality for patients who have severe MG. This medication should also be considered for use in treatment when standard immunosuppressive agents fail.