Treatments for Myasthenia Gravis

Commonly Used Treatments

Successful treatment requires a skilled physician overseeing management. Not all treatments are effective or viable options for all effected persons. Treatment must be individualized. Overall health history, disease presentation and severity, age, access to treatment, clinical skill and patient choice will all factor into medication management.This information is meant strictly as a guide. Always consult with a physician before making any changes to your medication regimen.

  • Pyridostigmine bromide (Mestinon) was the first FDA approved medication for Myasthenia Gravis and is commonly the first line drug, with the exception of MuSK antibody positive patients. It is an acetycholinesterase inhibitor that increases usable availability of acetycholine (neurotransmitter) in the synapse, temporarily allowing the muscle to receive a greater amount of the signal needed for improved, sustained contraction. The majority of patients will see positive improvement in varying degrees with Mestinon with a noticeable improvement in muscular weakness, although some will not take this medication in spite of effectiveness due to GI side effects.  Since there is no standard dosing regimen for Mestinon and since it poses the risk of cholinergic crisis (overdose), it is imperative to work with a knowledgeable care provider who will work with you on customizing a dose that is optimal for you.  Common symptoms are GI cramping, diarrhea, bloating, flatulence, increase in bronchial secretions and mild twitching.  Signs of an overdose are flushing, sweating, vomiting, severe GI cramping and diarrhea, salivation, lacrimation, unable to hold urine, twitching, sudden increase in generalized weakness, slurred speech and miosis.   

Please note that pyridostigmine bromide may contain large amounts of lactase that can aggravate patients who are lactose intolerant or allergic and is cautioned in the use of patients with asthma due to a possible increase in bronchial secretions and in patients with mechanical, intestinal or urinary obstruction. Please work with your care provider in determining the best course of action for your individual needs.

  • Corticosteroids (Prednisone, Prednisolone,  Methylprednisolone) are widely accepted and used in the treatment in autoimmune disease and Myasthenia Gravis. Notable improvement for Myasthenia patients occurs in an estimated 70 to 75% of the treated population. It is recommended that steroid treatment is begun at a lower rate and slowly increased so that the lowest therapeutic dose can be employed while reducing the potential for an acute Myasthenic exacerbaction as well as the risks and side effects commonly seen in steroid therapy.  Most patients will see a positive improvement in weakness within the first four to eight weeks of therapy with some enjoying drug induced remission from an appropriate dosing regimen. Thymoma and early onset myasthenics typically enjoy exceptional positive responses from steriod therapy both pre and post operatively. Side effects to steroid therapy can be difficult to tolerate and can range in severity and presentation. A patient's overall health history should be especially determined before beginning steroids. 
  • Immunosuppresants are steroid sparing drugs that are an option for patients who do not wish to be on long term steroid therapy or who need a more aggressive treatment option than what pyridostigmine and steroids alone can offer. (Please note that patients receiving immunosuppressants, are at increased risk of developing lymphoma and other  malignancies, particularly of the skin. Physicians should inform  patients of the risk of malignancy with therapeutic use.) These drugs carry the potential of fetal harm when administered to a pregnant woman. Whenever possible, immunosuppressants should not be given during pregnancy without careful weighing of risk versus benefit. The two most commonly used immunosuppresants are  azathioprine (Imuran) and  mycophenolate mofetil (Cellcept). A skilled provider will help the patient navigate which options are the best choice with the given health history and timeline for drug effiacy. Frequent monitoring with blood tests are necessary while on immunosuppressant therapy.
  • Azathioprine can take an average of three to six months to begin showing efficacy with some cases taking up to eighteen months to show maximal therapeutic responsiveness. This potential delay may act as a determinant for certain patients and their treating physicians. Not all will tolerate the side effects of this treatment. Many experience little to no side effects while enjoying strong, effective therapeutic use. Roughly one-third of treated patients experience mild dose-dependent side effects that does not necessitate stopping treatment but may require a reduction of the dosage.  Common side effects are  upset stomach, nausea, vomiting, diarrhea, loss of appetite, hair loss, or skin rash.    
  • Mycophenolate mofetil is generally well tolerated and has a similar mechanism of action as azathioprine. Both work by inhibiting B and T cell lymphocytes and help control mediated weakness. For those who do not respond well to azathioprine, mycophenolate mofetil may be an option depending on patient health history. Common side effects are mostly contained to GI disturbances such as cramping and diarrhea.  Mycophenolate mofetil carries with it an increased risk for certain types of cancer, nausea, vomiting, headaches, bone marrow suppression, sepsis, hypertension, tremor, neoplasia, depression, teratogenicity and an increased risk of infection.
  • Cyclosporine is another immunosuppresant option that is less commonly used than its counterparts due to lower patient tolerance but in some cases, it is a highly effective therapy option. Cyclosporine works by inhibiting predominantly T-lymphocyte-dependent immune responses and can sometimes prove effective in treating Myasthenia Gravis. While the majority of patients with Myasthenia Gravis show improvement on this medication within one to two months after starting therapy, it is poorly accepted outside of low therapeutic doses and comes with significant side effects. Like azathioprine, its efficacy and viability is maintained as long as appropriate, therapeutic doses are administered. Optimum improvement and stability is seen six months or longer after initiating the medication. After achieving the maximal response, the dose is titrated down to the minimum required to maintain improvement. It is very important to note that more adverse side effects are noted with this medication including renal toxicity and hypertension. Additionally, many drugs are contraindicated with cyclosporine and should be avoided or used with caution and physician oversight.   
  • Tacrolimus (Prograf) is another immunosuppressant drug that still requires further clinical investigation as to efficacy and patient tolerance. It can be combined with use of steroid and azathipine or mycophenolate mofetil therapy. Current research shows greatest patient response for those who are refractory (not responsive to attempted forms of therapy) and for newly diagnosed patients. Lowest therapeutic dosage is especially desirable since patient tolerance is not high with this treatment. 
  • IVIG/SCIG, also called gamma globulin or antibodies, is a highly purified blood product preparation that is derived from large pools of plasma donors and is administered via IV at home, in an infusion center or during a hospital admission and at home subcutaneously. Unlike immunosuppression and steroid therapy, which can be classified as chronic immunomodulating treatment, IVIG/SCIG can be classified as rapid immunomodulating treatments with a short duration of action and can be used for crisis intervention or long term patient management. It is also commonly used to help stabilize a patient for surgery or for post operative care, and to act as bridge to slower-acting therapies. It is not uncommon to see IVIG being used in addition to steroid and immunosuppression therapy.   As a blood product, this treatment carries risk of chemical aseptic meningitis, stroke, acute myocardial infarction, disseminated intravascular coagulation, transient serum sickness, transient neutropenia and thrombosis (rare). Patients with a history of stroke, CHF, clotting disorders, kidney, hepatic or cardiac disease should be well screened and cautiously considered before moving forward with IVIG. Serious adverse reactions occur in less than 5% of patients. The most common side effects occur soon after infusions and can include headache, flu like symptoms, GI cramping, flushing, chills, myalgia, wheezing, tachycardia, lower back pain, nausea, and hypotension. If these reactions present themselves, infusion should be stopped or slowed. If the infusion is resumed, a slower rate is suggested. Hydration pre, peri and post infusion and lower infusion rate is critical in helping to prevent adverse reactions.
  • Plasmapheresis (Plex) is a treatment similar to dialysis in which removal and return or exchange of plasma removes acetylcholine receptor (AChR) antibodies from the circulation of blood. Removed plasma is replaced with antibody free albumin and in some cases, fresh frozen plasma (for surgical and other health considerations). Steroid or immunosuppression therapy is encouraged in conjunction with plasmapheresis in order to help prevent antibody rebounding.  Plasmapheresis is used commonly to treat Myasthenic crisis. It is equally effective as IVIG in head to head studies in treating crisis at the one week mark post treatment, but at the three day mark, plasmapheresis shows a more rapid improvement with a shorter lasting duration, making it a more ideal treatment for rapid reversal in crisis. It is not frequently used for maintenance therapy, but it is a possibility for those who need a bridge in treatment but is not able to receive IVIG.  Benefits have a shorter duration of action with a mean benefit lasting 1-4 weeks depending on the individual. The procedure can be done in the hospital or at an infusion center. The most common side effects are hypotension (low blood pressure), which can manifest as dizziness, nausea and blurred vision, chills and hypocalcemia, which can manifest as muscle spasms and cramping, numbness and tingling in the hands, feet, and face and cardiac arrhythmia. Replacement calcium can be used to treat induced hypocalcemia.  

The Latest Pharmaceutical Therapies

Eculizumab (Soliris) is the first FDA approved treatment for Myasthenia Gravis in decades and one of only two FDA approved therapy options. It is also the latest treatment option in Myasthenia Gravis. This treatment works by binding to a particular protein that is involved in the immune system and subsequently inhibits one of the ways in which the immune system can attack the  neuromuscular junction (where Myasthenia Gravis manifests). This is indicated for use with AChR antibody positive patients who have failed previous therapies to adequately control their MG symptoms and have a more severe presentation. The risk for serious infection is present and the patient's health history should be well screened before beginning this treatment. 

Rituximab (Rituxan)  is a chimaeric monoclonal antibody specific for human CD20 that targets B lymphocytes. Originally developed for B-cell lymphoma, Rituximab was noted in clinical studies to also show benefit in some autoimmune diseases. Myasthenia Gravis has shown a history of B-cell hyperactivation which is believed to be a driving force behind antibody production. Rituximab is a new line of targeted therapy theorized to help halt or prevent this hyperactivation.  Currently studied for refractory and seronegative cases, Rituximab has shown great promise as an advancing therapy for Myasthenia Gravis. While many can tolerate it fairly well, it is an aggressive drug that comes with potentially serious risks and should be used with great caution and oversight by a skilled doctor who is experienced using Rituximab with Myasthenia Gravis.