Health Concerns

Myasthenia Gravis

Conventional Treatment

Fortunately, the majority of patients who have myasthenia gravis are able to be treated successfully and live normal lives. In some patients, temporary or permanent remission is possible and medications can be discontinued (MGFA 2010b). The choice of therapy depends on the type and severity of symptoms that the patient has and includes the following:

Acetylcholinesterase Inhibitors

Myasthenia gravis patients’ muscles are not able to respond properly to acetylcholine that is released from nerve cells. Therefore, treatments such as acetylcholinesterase inhibitors that increase levels of acetylcholine allow the muscle cells more time to respond to nerve impulses. Acetylcholinesterase inhibitors temporarily relieve symptoms, but will not block progression of the disease (Jayam Trouth 2012). They are usually used in patients with mild disease who present frequent symptoms and in patients with moderate disease in combination with immunosuppressant medication (Corse 2014). The most commonly prescribed acetylcholinesterase inhibitor is pyridostigmine bromide (Mestinon®, Regonol®); its side effects include diarrhea and stomach cramps. Drug overdose can lead to increased salivation, low heart rate, increased sweating, increased secretion of tears, and excessive pupil constriction (Meriggioli 2009). In patients who have antibodies to MuSK, acetylcholinesterase inhibitor treatment is typically less effective and may even result in worsening of symptoms (Corse 2014).

Plasma Exchange and Intravenous Immunoglobulin Therapy

Plasma is the liquid portion of the blood that transports blood cells and numerous other biomolecules. In plasma exchange, a patient’s plasma that contains self-antibodies is separated and removed from the remaining components of the blood. The removed plasma containing self-antibodies is usually replaced with plasma from donor individuals or a combination of albumin and saline (MGFA 2010a; Winters 2012). Plasma exchange can result in a rapid decrease in symptoms and is an important modality in the treatment of acute exacerbations; however, results are temporary. Side effects include decreased blood pressure, blood clots, infection, and an increased risk of bleeding (Jayam Trouth 2012).   

In immunoglobulin therapy, a patient suffering from myasthenia gravis is infused intravenously with antibodies isolated from human donors. The mechanism by which immunoglobulin therapy works is unclear, but it is believed that the infused antibodies block the activity of a number of different types of immune cells, including B cells, T cells, and macrophages. This is also a short-lived therapy, but it is highly effective at reducing symptoms of myasthenia gravis during exacerbation. Side effects are rare, but include blood clots (Jayam Trouth 2012). 

Plasma exchange and immunoglobulin therapy produce similar results and have similar side effects. However, the cost of immunoglobulin therapy is significantly greater than the cost of plasma exchange (Jayam Trouth 2012).

Immunosuppressants

The primary long-term treatment strategy for myasthenia gravis is suppression of the immune system, also known as immunosuppression (Sanders 2010). There are two classes of immunosuppressive agents commonly used: corticosteroids and non-steroidal drugs. Many myasthenia gravis patients must take immunosuppressive drugs indefinitely (Sieb 2014).

Corticosteroids. Corticosteroids are the most common immunosuppressive agents used to treat myasthenia gravis. They work extremely well to decrease symptoms; however, they only work for short periods of time and are associated with significant side effects (Sathasivam 2011). Prednisone is a steroidal drug typically used in patients with symptoms that cannot be controlled by acetylcholinesterase inhibitors (Meriggioli 2009). Approximately one-third of patients who take high doses of prednisone develop worsening of symptoms 7–10 days after the first administration. These symptoms can last for several days (Sathasivam 2011; UIC 2007; Meriggioli 2009). To prevent this complication, steroids should first be administered at low doses, on alternate days, and gradually increased over time.Alternatively, acetylcholinesterase inhibitors, plasma exchange, or immunoglobulin can also be used to treat these exacerbations (Meriggioli 2009). Side effects of corticosteroid use include high blood pressure, diabetes, osteoporosis, infection, psychiatric disorders, insomnia, and increased white blood cell count (Sathasivam 2011).

Non-steroidal agents. There are several different types of non-steroidal drugs used to treat myasthenia gravis.

  • Azathioprine (Imuran®, Azasan®) is effective in 70–90% of patients; however, benefits are not immediate and reductions in symptoms are often delayed by as long as 12 months. Azathioprine works by blocking T cells and B cells from dividing. It is often combined with prednisone in treatment strategies. Azathioprine has several severe side effects, including liver toxicity and a decrease in white blood cells. Fortunately, these side effects are reversible if drug concentration is reduced or treatment suspended. Azathioprine treatment can also increase the risk of developing different types of cancer (Meriggioli 2009). Azathioprine is generally the first choice agent for long-term immunosuppression in myasthenia gravis patients (Sieb 2014).
  • Cyclosporine (eg, Sandimmune®) works by blocking T cells from dividing. Cyclosporine side effects include tremors, anemia, hypertension, and kidney toxicity. It can also lead to an increased risk of developing cancer. A similar drug, Tacrolimus (Prograf®), also blocks T cells from increasing in number and has similar side effects as cyclosporine; however, it is associated with less kidney toxicity and the increase in blood pressure was less pronounced (Sakuma 2000; Mihatsch 1998; Meriggioli 2009; Thoms 2011).
  • Mycophenolate mofetil (CellCept®) is used to treat myasthenia gravis in some patients; however, efficacy has not been conclusively determined in large-scale, randomized controlled studies (Tavee 2010). Similar to azathioprine, mycophenolate mofetil works by blocking T and B cell multiplication (Meriggioli 2009). Despite many studies reporting that mycophenolate mofetil is effective in the treatment of myasthenia gravis (Sathasivam 2011), several clinical trials show that it is not more effective than prednisone in decreasing symptoms (Meriggioli 2009). Furthermore, a large clinical trial reported that treatment with mycophenolate mofetil has similar efficacy to treatment with a placebo (Sanders 2008). Common side effects associated with its use include headache, nausea, and diarrhea. Serious side effects may also occur such as infection, decreased white blood cell development, and liver toxicity (Sathasivam 2011).
  • Cyclophosphamide (eg, Cytoxan®) is a non-steroidal immunosuppressive agent that targets DNA and inhibits cell division (Johnson 2012). It is commonly used to treat different types of cancer including Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia (CLL), ovarian cancer, and breast cancer (MedlinePlus 2011). Clinical trials have found that cyclophosphamide is effective at improving symptoms of myasthenia gravis (Sanders 2010). A randomized, controlled trial in myasthenia gravis patients who failed other treatment options showed that prednisolone plus cyclophosphamide treatment resulted in significantly improved muscle strength at 12 months, but marginally at 6 months. The patients also were able to decrease their dosage of corticosteroid drugs at 6 and 12 months (De Feo 2002). Unfortunately, side effects of cyclophosphamide are severe because it is a non-specific agent and can damage normal dividing cells including those in the immune system, reproductive system, and gastrointestinal tract (Abarikwu 2012). Potential side effects include hair loss, nausea, vomiting, abdominal pain, and diarrhea (Jimenez 1992; RxList 2014). Cyclophosphamide treatment can also lead to severe side effects such as inhibition of immune function, bladder inflammation and bleeding, and an increased risk of infection and cancer (Sathasivam 2011; Sanders 2010). Due to these side effects, cyclophosphamide is only used in patients with severe myasthenia gravis who have shown no improvement with other treatment options (Sanders 2010).  

Thymectomy

Thymectomy, the surgical removal of the thymus, is a common treatment procedure for myasthenia gravis patients who have moderate to severe disease (Corse 2014). It is often performed in patients who have thymic tumors or hyperplasia, but is also performed in those who do not. Patients who have their thymus removed are more likely to achieve remission and become symptom free without medication than those who don’t. However, there is considerable debate about whether thymectomy is an effective and necessary option for patients without a thymoma (non-thymomatous). The remission rate for patients with non-thymomatous myasthenia gravis who undergo a thymectomy ranges from 38–72% (Diaz 2013). The first phase III randomized trial to determine if thymectomy is an effective treatment option in non-thymomatous myasthenia gravis patients is ongoing as of the time of this writing and preliminary results are expected in late 2015 (Cutter 2013). Removing the thymus gland may significantly impair one’s long term immune function (Bains 2013; Gerli 1999; Sauce 2009). Life Extension® suggests thymectomy be considered as a last resort.

Drugs to Avoid

Certain drugs may either induce symptoms of myasthenia gravis or aggravate existing symptoms. It is important to note that these cases are rare and patients should discuss the risks and benefits of all medications with their physician (MGFA 2014). Penicillamine is a drug commonly used to treat rheumatoid arthritis. Myasthenia gravis occurs in 1–7% of patients treated with penicillamine, with the first symptoms appearing 2–12 months after treatment initiation (UIC 2007).

High-dose intravenous magnesium can be used to treat pregnancy-induced preeclampsia. Clinical reports have shown that excessive intravenous magnesium can increase symptoms in myasthenia gravis patients and should be avoided (Cohen 1976; Catanzarite 1984; Bashuk 1990; MGFA 2014). Other drugs that may negatively impact myasthenia gravis include the antibiotics telithromycin (Ketek®), fluoroquinolones (ciprofloxacin and levofloxacin), azithromycin, gentamycin, and neomycin; botulinum toxin (Botox®); quinine; procainamide; and beta-blockers (MGFA 2014).