Myasthenia gravis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Medical Therapy
The mainstays of medical therapy for myasthenia gravis are:
Symptomatic treatments
An oral anticholinesterase like pyridostigmine is usually the first drug in MG patients.(5) these drugs can reduce the degradation of Ach in the synaptic cleft.(7) limbs and bulbar muscles respond very well to these drugs but ocular symptoms including diplopia are resistance to these medications.(8) (manabe az treatment)
Chronic immunomodulating treatments
- glucocorticoids: There are many studies supporting the beneficial effect of glucocorticoids like oral prednisone and pulsed intravenous (IV) methylprednisolone in MG patients. This group of drugs can improve the symptoms in almost 50 percent of patients.(6,7,8,11 chronic) the side effects of these drug are: Skin thinning and purpura(13), Cushingoid appearance and weight gain(4), cataracts and glaucoma(7), ischemic heart disease and heart failure(31), gastritis, ulcer formation, and gastrointestinal bleeding(48-49), menstrual irregularities in women and low fertility in both men and women(66-67) and psychiatric and cognitive symptoms(71).(manabe az avareze korton)
- immunosuppressive drugs
- Azathioprine: Azathioprine, a purine analogue which inhibits the nucleic acids synthesis, can cause improvement in about 90 percent of myasthenia gravis patients but the onset of this effect takes at least 6 to 12 month.(13-14-15-16 chronic) Azathioprine can cause macrocytosis (increased MCV) and malignancies such as non-hodgkin lymphoma. (19-20 chronic)
- Mycophenolate: Mycophenolate mofetil, a purine synthesis blocker in lymphocytes, is proven to be effective in reducing the symptoms of MG patients and their need to glucocorticoids.(25-26)
- Cyclosporine: Cyclosporine, an immunomodulatory agent which blocks the production of interleukin-2 and inhibits the function of T helper cells, can cause improvement in about 90 percent of MG patients after 1 to 2 months of start but the maximum effect will appear after 7 months.(32-33-34 chronic) This drug can cause nephrotoxicity (37), tremor, nausea, myalgias, gingival hyperplasia, hypertrichosis and malignancies such as squamous cell skin cancer and lymphoma.(34)
- Tacrolimus: Tacrolimus, an immunosuppressive macrolid can significantly reduce the requirement to prednisolone and MG symptoms in almost 67 to 87 percent of patients with less nephrotoxicity than cyclosporine.(37-38-40 ta44 chronic) the side effects of this drug include hyperglycemia, hypomagnesemia, paresthesias and tremor.(45)
- Rituximab: Rituximab, a monoclonal antibody against B cell membrane marker CD20 can be used in refractory myasthenia gravis. This drug is also effective in patients with anti MuSK antibody.(46-47-48-49-50 chronic)
- Methotrexate: Methotrexate is an immunosuppressant agent which suggested to be effective as a second line immunosuppressant for MG patients.(51-52)
- Etanercept: Etanercept is made of TNF receptor linked to Fc portion of human IgG1. This drug can inhibit TNF-alpha which is a proinflammatory cytokine, and improve the symptoms of MG patients.(53)
- Cyclophosphamide: Cyclophosphamide is an alkylating agent which inhibits the proliferation of B and T cells. Monthly high dose intravenous administration of this drug is proved to be more effective than daily oral type.(54) the side effects of this drug include anorexia, nausea and vomiting, leukopenia, alopecia and hemorrhagic cystitis and it can also increase the risk of malignancies.(54-55)
Rapid immunomodulating treatments
- plasmapheresis
- intravenous immune globulin