Myasthenia gravis is a neuromuscular disorder driven by autoimmunity against the postsynaptic neuromuscular junction of skeletal muscles. The clinical manifestations of myasthenia gravis are broad, but generally it can be characterized as being fluctuating, chronic, and oftentimes carrying a poor prognosis. 

“[Myasthenia gravis] impairs [neuromuscular junction] transmission and can manifest in a spectrum ranging from mild ptosis and ocular symptoms to profound bulbar, limb and respiratory muscle weakness, and the presentation can be broadly classified as ocular or generalized [myasthenia gravis],” Menon and Bril wrote in Drugs. 

Read more about myasthenia gravis etiology 

Epidemiological studies suggest that the prevalence of myasthenia gravis is increasing. This can be due to a few factors: diagnostic protocols have been refined in recent years, making cases of myasthenia gravis harder to miss. In addition, novel therapies have extended the lifespan of patients with myasthenia gravis. Combined, this means that there is a higher percentage of patients with myasthenia gravis among the patient population. 

Ever since myasthenia gravis has been classified as an autoimmune disorder, therapeutic strategies have focused on immunomodulation or immunosuppression. The treatment goal for myasthenia gravis is also well-defined: achieving the complete remission of the disease or minimal manifestation of symptoms. 

In other autoimmune diseases, the therapeutic goal is much more ambitious, namely the complete eradication of the disease. This concept is known as “disease freedom”. However, in myasthenia gravis, this is currently unachievable, although patients can enjoy periods of sustained remission if prescribed the right therapies. 

Because there are a legion of immunosuppressive therapies available, many have been experimented on in patients with myasthenia gravis, with varying results. For example, current treatments include those that target the complement cascade, B and T cells, and cytokines associated with antibody production. 

Considerations in Clinical Trials  

“As the arsenal of [myasthenia gravis] immunosuppressive therapies increases, choosing a treatment that is targeted to the individual patient becomes more difficult,” wrote Lascano and Lalive in Autoimmunity Reviews. 

While the body of medical literature on myasthenia gravis is considerable, on closer inspection clinical trial designs and methodologies are incredibly heterogenous. In addition, the nature of the disease — fluctuating, with varying degrees of severity — makes it challenging to apply existing clinical study findings to any one patient. 

“Most of the recent [myasthenia gravis] clinical trials have recruited adult patients with [acetylcholine receptor] antibody-positive generalized [myasthenia gravis] who have been on stable doses of corticosteroids (typically for 4 weeks) or conventional immunosuppressive agents for 3–6 months,” Menon and Bril wrote. 

On the flip side, this means that studies tend to exclude patients who have undergone a recent thymectomy, patients requiring maintenance of intravenous immunoglobulin, or those requiring therapeutic plasma exchange. As a result, the clinical safety and efficacy of certain drugs in particular populations of patients remain uncertain. 

In addition, Menon and Bril highlight a few other points that make it challenging to conduct clinical trials among patients with myasthenia gravis. For example, there are no ideal biomarkers for myasthenia gravis; antibody levels do not necessarily translate to clinical severity. In addition, single-fiber electromyography can yield important data regarding neuromuscular transmissions, but it is both time-consuming and invasive, making it impractical in a clinical trial setting. 

Instead, clinicians have had to rely on a series of scoring systems to determine the impact of experimental drugs on clinical outcomes. These include Quantitative Myasthenia Gravis, Myasthenia Muscle Score, and Manual Muscle Test. Researchers also rely on quality of life questionnaires such as Myasthenia Gravis Quality of Life and Myasthenia Gravis Activities of Daily Living. 

“Despite all these instruments, a single gold standard trial design for [myasthenia gravis] is still not feasible,” opined Menon and Bril. “Furthermore, current trial designs fail to address multiple relevant questions concerning initiation and discontinuation of novel agents, inter-class and intra-class switching, synergistic or antagonistic actions and application in vulnerable populations.” 

Current Therapies 

Nevertheless, the starting point that views myasthenia gravis as an autoimmune disorder means that many of the current therapies were created with this paradigm in mind. For example, steroid therapy has been a staple of myasthenia gravis treatment for the last 6 decades, producing a favorable clinical response in around 66% of patients. 

Steroid therapy is thought to work by inhibiting T-cell and monocyte-macrophage activation (as opposed to reducing antibody levels). High-dose intravenous pulse corticosteroids have been found to achieve a faster clinical response with fewer side effects compared to short-term daily regimens. 

“Even though steroids are meant to be a short-term treatment, this drug is not usually discontinued,” Lascano and Lalive wrote. 

This, of course, puts patients at risk of developing adverse effects associated with long-term steroid use, which usually leads to the initiation of steroid-sparing agents. If steroids do not produce an adequately favorable clinical response within the first year, physicians usually switch to nonsteroidal immunosuppressive drugs. 

Another immunosuppressive agent widely used in myasthenia gravis is azathioprine (Imuran®). It works by inhibiting cellular synthesis and replication, limiting the proliferation of lymphocytes. Studies suggest that azathioprine alone works just as effectively as a combination of azathioprine and corticosteroid therapy. Current protocol dictates that azathioprine monotherapy is best suited in patients with non-turbulent disease, given its gradual onset of action.

Read more about myasthenia gravis treatment 

Importantly, azathioprine is generally safe and well-tolerated. It is also considered safe during pregnancy. In clinical practice, it is usually prescribed if patients cannot tolerate corticosteroid therapy. 

The treatment of myasthenia gravis via an immunosuppressive lens has served patients well in the last half-century or so. However, the research community is poised to go beyond this paradigm and introduce treatments that have far greater specificity. The trend today is to shift towards target-specific and selective immunological agents instead of broad-spectrum immunosuppressant agents. In the years ahead, we will likely see the increasing personalization of therapies for patients with myasthenia gravis. 


Menon D, Bril V. Pharmacotherapy of generalized myasthenia gravis with special emphasis on newer biologicalsDrugs. Published online May 31, 2022. doi:10.1007/s40265-022-01726-y

Lascano AM, Lalive PH. Update in immunosuppressive therapy of myasthenia gravisAutoimmun Rev. Published online December 16, 2020. doi:10.1016/j.autrev.2020.102712