Yuebing Li, MD

Dr Li is a staff physician, Department of Neurology, Neuromuscular Center, Neurological Institute at the Cleveland Clinic, Cleveland, OH.

Considered the most common primary disorder of neuromuscular transmission, myasthenia gravis (MG) has an incidence of 5 to 10 cases per million per year; the resulting prevalence is 36,000 to 60,000 cases in the US and more than 700,00 worldwide. Demographically, about 75% of patients under age 40 are women, while men represent the majority of cases (60%) in those older than 40.

Although there is no known cure, treatment controls symptoms, allowing most patients to have a relatively high quality of life and may lead to symptom remission in patients. Due to MG’s heterogeneity, treatment regimens should be individualized based on each patients’ symptoms, needs, and the like.

MG disease classifications and their impact on treatment

Based on areas of involvement, MG can be divided into ocular (only affecting muscles around the eye) and generalized (affecting other muscles such as muscles to control speech, chewing, swallowing, neck position, arms, and legs) subtypes.

In approximately 70% of cases, eye symptoms (droopy eyelids or double vision) are the presenting signs of MG. Only in a small portion (15% of patients), symptoms and signs remains exclusively in the eye region, and in the majority of patients, a generalized form will develop, mostly within the first three years.

In general, the ocular form is milder when compared with the generalized form, therefore less aggressive treatment is needed. However, immunosuppressive treatment is still needed in most patients with ocular MG, but a lower dose of a shorter duration might suffice.

It is important to know the differential diagnoses for MG and coexisting diagnoses in any given patient to avoid mixing MG symptoms with symptoms of other disorders.

On the other hand, patients with generalized MG often require immunosuppression of sufficient dosage and duration. In patients with severe generalized MG including those with myasthenic crisis (requiring ventilation), aggressive treatment that includes high-dose corticosteroid, intravenous immunoglobulin, and/or plasmapheresis is often needed.

MG is an antibody-mediated illness, and it also can be classified based on antibody types. The most common subtype is the antibody against acetylcholine receptor (AChR), seen in approximately 85% of patients. Another antibody acts against muscle-specific receptor tyrosine kinase (MuSK). Patients with anti-MuSK MG could have a more regional and more severe form of MG that is difficult to treat. Other newly discovered antibodies may include antibodies against lipoprotein-related protein 4 (LRP4). Patients with antibodies against LRP4 usually have a milder form of MG.

Symptomatic treatment for MG primarily includes the use of acetylcholinesterase (AChE) inhibitors such as pyridostigmine. The goal is to improve the patient’s symptoms. Such treatment may facilitate the recovery of body function, but in general does not change the underlying course of the illness.

Because MG is an autoimmune disease, various immunosuppressive treatments (including corticosteroids, azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclosporine, cyclophosphamide, rituximab, intravenous immunoglobulin [IVIG] and plasmapheresis) are used to induce symptom remission and prevent relapse.

General health and supportive treatments (good rest and sleep, healthy diet, moderate exercise, and avoidance of infection) are necessary to prevent relapse or exacerbation and promote the body’s own recovery of function. In general, these treatments do not change the underlying course of the illness.

The most effective treatment for most MG patients is a corticosteroid such as prednisone or prednisolone. In patients who cannot tolerate corticosteroids, other immunosuppressive medications such as azathioprine, mycophenolate mofetil, or tacrolimus should be considered. Often a combination of corticosteroid and these immunosuppressive medications is used to minimize possible adverse effects from corticosteroids.

In patients with severe symptoms, the use of intravenous immunoglobulin (IVIG) or plasmapheresis can often reduce the requirement for corticosteroids and lead to rapid improvement. In patients with refractory MG (defined as treatment response failure to corticosteroid and two other immunosuppressive agents), rituximab or cyclophosphamide is often considered.

There are three main factors that contribute to patient nonadherence to medications.

1. The first is patients’ fear. Patients often have heard a lot about possible adverse effects of immunosuppressive agents. It is important for patients to learn that most patients will tolerate these medications without significant adverse effects as long as the medications are being managed appropriately.

2. The second factor is the physician’s unfamiliarity with the medication. It is important for prescribers to learn about these medications in detail and get acquainted with the common adverse effects.

3. The third is possible coverage limitations from insurance companies.

To improve adherence, it is better to start these medications at a low dosage, followed by gradual titration. It is important for a physician’s office to set up a protocol specifying the timing and need of monitoring common adverse effects for each medication. Finally, it is often helpful to arrange more frequent office visits for patients with a new diagnosis of MG.

Guptill JT, Soni M, Meriggioli MN. Current treatment, emerging translational therapies, and new therapeutic targets for autoimmune myasthenia gravis. 

Howard JF. Clinical Overview of Myasthenia Gravis. 2015. Available at: http://www.myasthenia.org/HealthProfessionals/ClinicalOverviewofMG.aspx. Accessed July 20, 2017.

Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: executive summary. 

http://emedicine.medscape.com/article/1171206-overview

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The author discusses MG disease classifications as well as treatment goals and treatment adherence.

Yuebing Li, MD

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