Introduction to Myasthenia Gravis and Its Impact

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness and fatigue, primarily impacting skeletal muscle function. The condition arises due to the immune system’s production of antibodies that target acetylcholine receptors (AChRs) at the neuromuscular junction, leading to impaired communication between nerves and muscles (1). The fluctuating nature of muscle weakness can significantly disrupt daily activities, affecting the quality of life for those affected. The disorder can manifest in various forms, including ocular myasthenia gravis, which primarily affects the eye muscles, and generalized myasthenia gravis, which involves more widespread muscle weakness (2).

The psychological burden of MG is profound, as patients often face challenges related to physical limitations and the unpredictability of symptoms. This can lead to anxiety and depression, compounding the overall impact of the disease. Current treatment options include acetylcholinesterase inhibitors, thymectomy, and immunosuppressive therapies, yet these approaches often leave room for improvement in terms of efficacy and safety (3, 4).

Current Treatment Options and Their Limitations

Historically, the management of MG has relied on acetylcholinesterase inhibitors, which enhance neuromuscular transmission by prolonging the action of acetylcholine at the neuromuscular junction. While this approach can provide symptomatic relief, it does not address the underlying autoimmune processes (5). Immunosuppressive therapies, including corticosteroids and non-steroidal immunosuppressants (NSISTs), are frequently employed to control the immune response. However, these treatments can lead to severe long-term side effects, including infections, osteoporosis, and metabolic changes (6, 7).

Thymectomy, the surgical removal of the thymus gland, has been shown to benefit a subset of patients, particularly those with thymoma or generalized MG. Despite these options, many patients remain refractory to standard treatments, highlighting the urgent need for more effective and targeted therapies (8, 9).

Advancements in Targeted Biologic Therapies

Recent advancements in the understanding of MG’s pathophysiology have paved the way for targeted biologic therapies that directly inhibit the pathogenic mechanisms at play (10). These therapies focus on modulating specific immune pathways involved in the disease’s progression, offering a promising alternative to traditional immunosuppressants.

Efgartigimod, an FcRn antagonist, exemplifies a novel biologic that has demonstrated efficacy in reducing pathogenic antibody levels associated with MG. By binding to FcRn receptors, efgartigimod disrupts the recycling of IgG, leading to a swift decrease in the levels of harmful antibodies. Clinical trials have shown that patients receiving efgartigimod experience significant improvements in muscle strength and functional outcomes, with a favorable safety profile (11, 12).

Another innovative approach involves complement inhibition, with therapies such as eculizumab and ravulizumab targeting the complement cascade to prevent muscle damage. These complement inhibitors have shown considerable promise in treating generalized MG, particularly in patients who are refractory to traditional treatments (13, 14).

These biologics represent a significant paradigm shift in the management of MG, moving from a primarily symptomatic treatment approach to one that targets the underlying mechanisms of the disease.

The Role of Efgartigimod and Telitacicept in Therapy

Efgartigimod’s rapid action and ability to provide significant symptom relief have made it a cornerstone of modern MG therapy (15). However, the transient nature of its effects necessitates the development of strategies for maintaining long-term disease control. This is where telitacicept, a recombinant fusion protein that inhibits B cell survival and differentiation, comes into play (16).

Telitacicept acts by blocking the activity of BAFF and APRIL, crucial factors for B cell maturation. By targeting this pathway, telitacicept reduces the population of long-lived plasma cells responsible for autoantibody production, addressing a key aspect of MG pathophysiology (17). Clinical studies have demonstrated telitacicept’s safety and efficacy across various antibody-mediated autoimmune diseases, including promising results in generalized MG (18).

The potential for a sequential therapy approach utilizing efgartigimod followed by telitacicept is currently under investigation. This strategy aims to leverage efgartigimod’s rapid antibody clearance followed by telitacicept’s sustained B cell modulation, potentially offering a more durable and comprehensive treatment regimen for patients with MG (19).

Future Directions in Myasthenia Gravis Research and Treatment

Research into MG continues to evolve, with a focus on identifying biomarkers that can guide treatment decisions and improve patient outcomes. Understanding the genetic and immunological underpinnings of the disease will be crucial in developing personalized treatment strategies that cater to the unique profiles of patients.

The exploration of combination therapies, including targeted biologics and traditional immunosuppressants, presents an exciting avenue for enhancing treatment efficacy while minimizing side effects. Future clinical trials will play a vital role in validating these approaches and establishing guidelines for their use in clinical practice (20).

Additionally, ongoing studies are needed to evaluate the long-term safety and efficacy of emerging therapies, as well as their impact on the psychological well-being of patients. Addressing the mental health aspects of MG is essential for providing holistic care and improving the overall quality of life for individuals living with this challenging condition.

FAQ

What is Myasthenia Gravis?

Myasthenia gravis (MG) is a chronic autoimmune disorder that leads to weakness and fatigue of voluntary muscles due to the immune system attacking acetylcholine receptors at the neuromuscular junction.

What are the common symptoms of MG?

Common symptoms of MG include fluctuating muscle weakness, especially in the eyes, face, throat, and limbs. Patients may experience drooping eyelids, double vision, difficulty swallowing, and general fatigue.

How is MG treated?

MG is primarily treated with acetylcholinesterase inhibitors, immunosuppressive therapies, and thymectomy. Recent advancements include targeted biologic therapies such as efgartigimod and telitacicept.

What is efgartigimod?

Efgartigimod is an FcRn antagonist that reduces pathogenic antibody levels by disrupting their recycling, leading to improved muscle strength in patients with MG.

What is telitacicept?

Telitacicept is a recombinant fusion protein that inhibits B cell survival and differentiation, reducing the production of autoantibodies in patients with MG.

What are the future directions for MG research?

Future research will focus on identifying biomarkers for personalized treatment, exploring combination therapies, and studying the long-term effects of new biologics on both physical and mental health outcomes for patients with MG.

References

Efgartigimod Followed by Telitacicept in Adult Generalized Myasthenia Gravis: A Retrospective Case Series. Retrieved from https://doi.org/10.2147/JIR.S513986
Psychosocial stress and cardiovascular disease. Retrieved from https://doi.org/10.1016/j.ajpc.2025.100968
Antimicrobial peptides selectively target malaria parasites by a cholesterol-dependent mechanism. Retrieved from https://doi.org/10.1016/j.jbc.2025.108298
Characterization of NAT, GST, and CYP2E1 Genetic Variation in Sub‐Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11993289/
Investigation of Genomic and Transcriptomic Risk Factors of Clopidogrel Response in African Americans. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11993291/