Understanding Myasthenia Gravis

At OptiMyG, we are dedicated to transforming the future for patients with new-onset myasthenia gravis. Let's dive into what this condition is all about.

The need for research

We are conducting this study to better understand myasthenia gravis (MG) and improve treatment options for patients. While current therapies can help manage symptoms, they do not work equally well for everyone, and some can have significant side effects.

Our study aims to explore how early treatment with immune-suppressing therapies, like rituximab, impacts the course of the disease. We want to find out if it can reduce symptoms, prevent the disease from escalating, and lower the need for hospitalizations.

We are also studying the role of specific antibodies in MG to understand how they change over time and how they respond to treatment. This could help us predict which treatments will work best for individual patients in the future, moving closer to personalized care for MG.

What is myasthenia gravis?

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating muscle weakness, particularly in muscles responsible for eye movements, facial expressions, mastication, swallowing, and speech.

MG is a rare condition, with an estimated prevalence of approximately 25 cases per 100,000 individuals. It can occur at any age but is more frequently observed in young adult women and in individuals of both sexes over the age of 60.

Distinct subtypes of MG are recognized:

  • Early-onset MG (EOMG): Predominantly affects women and typically manifests between the ages of 20 and 40. This subtype is often associated with thymic hyperplasia (enlargement of the thymus gland).
  • Late-onset MG (LOMG): More common in men, it usually begins around the age of 70 and is generally not linked to thymus abnormalities.

The hallmark of MG is muscle weakness that fluctuates over time, improving with rest but worsening with activity. Clinical severity ranges from isolated ocular symptoms, such as drooping eyelids (ptosis) and double vision (diplopia), to generalized muscle weakness involving limb and respiratory muscles, which may lead to life-threatening myasthenic crises.

The disease often presents initially with ocular or facial muscle involvement, resulting in ptosis, difficulties in facial expressions, and impaired chewing or speaking. Over time, the weakness may spread to other muscle groups. Symptom severity may vary throughout the day and can be exacerbated by factors such as physical or emotional stress, infections, or certain medications.

What do we know so far?

The weakness in MG happens because the body’s immune system produces antibodies that disrupt signal between nerves and muscles. Around 80% of people with MG  have antibodies that attack a protein called the acetylcholine receptor (AChR), while smaller groups have antibodies against other proteins, such as muscle-specific kinase (MuSK) or lipoprotein receptor-related protein 4 (LRP4). Some people, about 10–20%, do not have detectable antibodies to these known proteins, and this is called “triple-seronegative MG.” 

The exact cause of MG is not known, but both heredity and environmental factors, such as infections, are believed to play a role. 

Current treatment

Cholinesterase inhibitors are often used as a first treatment to improve MG symptoms by increasing acetylcholine levels, but long-term immunotherapies are usually needed for preventing worsening. Corticosteroids like prednisolone are the first choice for immunomodulation, but their long-term use often causes serious side effects. As a result, steroid-sparing drugs, including azathioprine and mycophenolate, are commonly used, though scientific evidence supporting them is limited. Unfortunately, this leaves a great proportion of MG patients with significant residual symptoms. 

Biological treatments such as :

  • Complement inhibitors (eculizumab, ravalizumab)
  • Fc receptor blockers (efgartigimod)

are available only as a third line option for AChR positive patients, but are costly and not widely accessible.

Rituximab, a B-cell (a type of white blood cell that produce antibodies) depleting therapy, has shown promise in early studies, particularly for MuSK-positive MG, and may reduce the risk of worsening symptoms if used early. 

Why rituximab?

Rituximab is a humanized chimeric  monoclonal antibody, meaning it was created by combining human and non-human components to specifically target a protein called CD20 found on certain immune cells (B cells). Rituximab  has been long used to treat various lymphoproliferative and autoimmune disorders. Rituximab in MG has been studied in several meta-analyses and randomised, double-blind, placebo-controlled clinical trials, with conflicting results due to heterogeneous methods and study designs. Our study aims to find out if there is a window of opportunity to mitigate long-term disease burden by early depletion of B cells to prevent buildup of a long-lived plasma cell pool, and to inform on the long-term benefit-risk balance.

References
  1. Alvarez-Velasco R, Dols-Icardo O, El Bounasri S, et al. Reduced Number of Thymoma CTLA4-Positive Cells Is Associated With a Higher Probability of Developing Myasthenia Gravis. Neurol Neuroimmunol Neuroinflamm. Mar 2023;10(2)doi:10.1212/NXI.0000000000200085
  2. Bhandari V, Bril V. FcRN receptor antagonists in the management of myasthenia gravis. Front Neurol. 2023;14:1229112. doi:10.3389/fneur.2023.1229112
  3. Cortes-Vicente E, Alvarez-Velasco R, Pla-Junca F, et al. Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome. Annals of clinical and translational neurology. Feb 2022;9(2):122-131. doi:10.1002/acn3.51492
  4. Cortes-Vicente E, Alvarez-Velasco R, Segovia S, et al. Clinical and therapeutic features of myasthenia gravis in adults based on age at onset. Mar 17 2020;94(11):e1171-e1180. doi:10.1212/WNL.0000000000008903
  5. Dalakas MC. Immunotherapy in myasthenia gravis in the era of biologics. Nat Rev Neurol. Feb 2019;15(2):113-124. doi:10.1038/s41582-018-0110-z
  6. Evoli A, Spagni G, Monte G, Damato V. Heterogeneity in myasthenia gravis: considerations for disease management. Expert Rev Clin Immunol. Jul 2021;17(7):761-771. doi:10.1080/1744666X.2021.1936500
  7. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J. Myasthenia gravis. Nat Rev Dis Primers. May 2 2019;5(1):30. doi:10.1038/s41572-019-0079-y
  8. Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis – autoantibody characteristics and their implications for therapy. Nat Rev Neurol. May 2016;12(5):259-68. doi:10.1038/nrneurol.2016.44
  9. Grob D, Brunner N, Namba T, Pagala M. Lifetime course of myasthenia gravis. Muscle Nerve. Feb 2008;37(2):141-9. doi:10.1002/mus.20950
  10. Narayanaswami P, Sanders DB, Wolfe G, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. Jan 19 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124
  11. Nowak RJ, Coffey CS, Goldstein JM, et al. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology. Dec 22021;doi:10.1212/WNL.0000000000013121
  12. Piehl F, Eriksson-Dufva A, Budzianowska A, et al. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA neurology. Nov 1 2022;79(11):1105- 1112. doi:10.1001/jamaneurol.2022.2887
  13. Rath J, Brunner I, Tomschik M, et al. Frequency and clinical features of treatment-refractory myasthenia gravis. J Neurol. Apr 2020;267(4):1004-1011. doi:10.1007/s00415-019-09667-5
  14. Rose N, Holdermann S, Callegari I, et al. Receptor clustering and pathogenic complement activation in myasthenia gravis depend on synergy between antibodies with multiple subunit specificities. Acta Neuropathol. Nov 2022;144(5):1005-1025. doi:10.1007/s00401-022-02493-6

Discover our latest publications

Cellular immune endophenotypes separating early and late-onset myasthenia gravis.

Theorell J, Ruffin N, Fower A, Sorini C, Ambrose P, Damato V, Handunnetthi L, Leite I, Irani SR, Brauner S, Handel AE, Piehl F. JCI Insight. 2025; e199679. doi: 10.1172/jci.insight.199679. Online ahead of print. PMID: 41307955

OptiMyG partners Stockholm and Firenze, with additional contribution of Oxford, UK

Early- and late-onset myasthenia gravis differ immunologically despite sharing acetylcholine-receptor antibodies. Using deep cytometric and single-cell phenotyping of blood and thymus samples, the study identified three lymphocyte populations that distinguish the subgroups: mucosa-associated invariant T cells and naïve CD8 T cells were reduced in late-onset disease, indicating immune senescence, while a differentiated NK-cell population was specifically decreased in early-onset disease and correlated with thymic inflammation. Using only these three populations, subgroup prediction reached 90% accuracy. These findings reveal distinct immunocellular endophenotypes that may enhance disease classification and guide targeted interventions.

 

 

Nicotine, Alcohol Consumption, and Risk of Myasthenia Gravis: Results From the Swedish Nationwide GEMG Study

Petersson, M., Jons, D., Feresiadou, A., Ilinca, A., Lundin, F., Johansson, R., Budzianowska, A., Roos, A.-K., Kagström, V., Gunnarsson, M., Sundström, P., Klareskog, L., Olsson, T., Kockum, I., Piehl, F., Alfredsson, L., Brauner, S.

Neurology. 2025;105(1):e213771.

OptiMyG partner Stockholm

Alcohol consumption was associated with a lower risk of myasthenia gravis in this nationwide Swedish case-control study, while nicotine exposure showed subtype-specific effects. Smoking and use of Swedish snuff at disease onset increased the risk of early-onset MG, particularly in acetylcholine receptor antibody–positive cases. No association with nicotine was seen in late-onset disease. Despite limitations of retrospective self-reported data, the findings suggest that alcohol may be protective, whereas nicotine exposure may contribute to MG risk, especially in younger patients.

Comparison of the Quantitative Myasthenia Gravis and Myasthenia Gravis Activity of Daily Living Scores From a Clinical Practice Perspective

Wu, W., Petersson, M., Piehl, F., Brauner, S. Muscle Nerve. 2025;72(5):1100-1107. doi: 10.1002/mus.70013.

OptiMyG partner Stockholm

Summary; MG-ADL and QMG showed notable differences in how they capture disease activity in myasthenia gravis. In 177 patients, MG-ADL detected residual symptoms more often than QMG, especially for bulbar and respiratory complaints, and showed a lower flooring effect. QMG scores were associated with disease onset, MG-QoL-15, and prior prednisolone use, while MG-ADL correlated only with MG-QoL-15. Quality-of-life influences were driven by symptom-related items. Overall, MG-ADL appears more sensitive in mild disease, whereas QMG reflects more objective clinical factors, highlighting their complementary roles for assessing MG severity.

Rituximab in New-Onset Generalized Myasthenia Gravis: Long-Term Follow-Up of the RINOMAX Clinical Trial

Wu, J., Eriksson-Dufva, A., Budzianowska, A., Feresiadou, A., Hansson, W., Hietala, M.A., Håkansson, I., Johansson, R., Jons, D., Kmezic, I., Lindberg, C., Lindh, J., Lundin, F., Nygren, I., Rostedt Punga, A., Press, R., Samuelsson, K., Sundström, P., Wickberg, O., Frisell, T., Brauner, S., Piehl, F.

Eur J Neurol. 2025;32(11):e70418. doi: 10.1111/ene.70418

OptiMyG partner Stockholm

The long term follow-up of the RINOMAX randomized clinical trial in new-onset generalized myasthenia gravis suggests sustained benefit of rituximab beyond the first year. Early rituximab treatment led to lower QMG scores at 12 and 24 months, fewer hospitalizations, and fewer rescue treatments compared with placebo or delayed rituximab. Rescue needs over 5 years were numerically lower with early rituximab, and corticosteroid use remained low. Severe infections occurred in 12–19% of rituximab-treated patients, highlighting safety considerations. Overall, long-term disease activity and treatment burden were low, suggesting a favorable long-term effect of rituximab, though infection risk with B-cell depletion warrants caution.

Impact of disease activity on quality of life and EQ-5D-3L score in myasthenia gravis: results from the Swedish MG registry

Petersson, M., Wu, J., Berggren, F., Schager, I., Piehl, F., Brauner, S.

J Neurol. 2025;272(9):562. doi: 10.1007/s00415-025-13298-4.

OptiMyG partner Stockholm

Quality of life was substantially reduced in myasthenia gravis, even at low disease activity. EQ-5D scores were significantly lower than in the general population and correlated with MG-ADL, QMG, and MG-QoL-15. The greatest impairment was in usual activities, with limb and respiratory symptoms driving most of the QoL reduction. Longitudinal data showed that each increase in MG-ADL score corresponded to a measurable decline in EQ-5D. These findings highlight that MG impacts daily functioning early in the disease course, underscoring the need for improved treatment strategies.

Our previous publications:

 

  1. Álvarez-Velasco R, Dols-Icardo O, El Bounasri S, López-Vilaró L, Trujillo JC, Reyes-Leiva D, Suárez-Calvet X, Cortés-Vicente E, Illa I, Gallardo E. Reduced number of thymoma CTLA4-positive cells is associated with a higher probability of developing myasthenia gravis. Neurology: Neuroimmunology & Neuroinflammation. 2023 Jan 25;10(2):e200085.
  2. Caballero-Ávila M, Álvarez-Velasco R, Moga E, Rojas-Garcia R, Turon-Sans J, Querol L, Olivé M, Reyes-Leiva D, Illa I, Gallardo E, Cortés-Vicente E. Rituximab in myasthenia gravis: efficacy, associated infections and risk of induced hypogammaglobulinemia. Neuromuscular Disorders. 2022 Aug 1;32(8):664-71.
  3. Cortes-Vicente E, Alvarez-Velasco R, Pla-Junca F, et al. Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome. Annals of clinical and translational neurology. Feb 2022;9(2):122-131. doi:10.1002/acn3.51492
  4. Cortes-Vicente E, Alvarez-Velasco R, Segovia S, et al. Clinical and therapeutic features of myasthenia gravis in adults based on age at onset. Mar 17 2020;94(11):e1171-e1180. doi:10.1212/WNL.0000000000008903
  5. Damato V, Spagni G, Monte G, Scandiffio L, Cavalcante P, Zampetti N, Fossati M, Falso S, Mantegazza R, Battaglia A, Fattorossi A. Immunological response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis treated with rituximab. Neuromuscular Disorders. 2023 Mar 1;33(3):288-94.
  6. Damato V, Spagni G, Monte G, Woodhall M, Jacobson L, Falso S, Smith T, Iorio R, Waters P, Irani SR, Vincent A. Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis. Journal of Neurology, Neurosurgery & Psychiatry. 2022 Sep 1;93(9):995-1000.
  7. Farina A, Falso S, Cornacchini S, Spagni G, Monte G, Mariottini A, Massacesi L, Barilaro A, Evoli A, Damato V. Safety and tolerability of SARS‐Cov‐2 vaccination in patients with myasthenia gravis: A multicenter experience. European Journal of Neurology. 2022 Aug;29(8):2505-10.
  8. Mariscal A, Martínez C, Goethals L, Cortés-Vicente E, Moltó E, Juárez C, Barneda-Zahonero B, Querol L, Le Panse R, Gallardo E. Modified radioimmunoassay versus ELISA to quantify anti-acetylcholine receptor antibodies in a mouse model of myasthenia gravis. Journal of Immunological Methods. 2024 Nov 1;534:113748.
  9. Piehl F, Eriksson-Dufva A, Budzianowska A, et al. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA neurology. Nov 1 2022;79(11):1105- 1112. doi:10.1001/jamaneurol.2022.2887
  10. Reyes-Leiva D, López-Contreras J, Moga E, Pla-Juncà F, Lynton-Pons E, Rojas-Garcia R, Turon-Sans J, Querol L, Olive M, Álvarez-Velasco R, Caballero-Ávila M. Immune response and safety of SARS-CoV-2 mRNA-1273 vaccine in patients with myasthenia gravis. Neurology: Neuroimmunology & Neuroinflammation. 2022 Jun 20;9(4):e200002.
  11. Reyes-Leiva D, López-Contreras J, Moga E, Pla-Juncà F, Lynton-Pons E, Rojas-Garcia R, Turon-Sans J, Querol L, Olive M, Álvarez-Velasco R, Caballero-Ávila M. Immune response and safety of SARS-CoV-2 mRNA-1273 vaccine in patients with myasthenia gravis. Neurology: Neuroimmunology & Neuroinflammation. 2022 Jun 20;9(4):e200002.
  12. Rose N, Holdermann S, Callegari I, et al. Receptor clustering and pathogenic complement activation in myasthenia gravis depend on synergy between antibodies with multiple subunit specificities. Acta Neuropathol. Nov 2022;144(5):1005-1025. doi:10.1007/s00401-022-02493-6
  13. Spagni G, Gastaldi M, Businaro P, Chemkhi Z, Carrozza C, Mascagna G, Falso S, Scaranzin S, Franciotta D, Evoli A, Damato V. Comparison of fixed and live cell-based assay for the detection of AChR and MuSK antibodies in myasthenia gravis. Neurology: Neuroimmunology & Neuroinflammation. 2022 Oct 21;10(1):e200038.
  14. Spagni G, Vincent A, Sun B, Falso S, Jacobson LW, Devenish S, Evoli A, Damato V. Serological Markers of Clinical Improvement in MuSK Myasthenia Gravis. Neurology: Neuroimmunology & Neuroinflammation. 2024 Sep 9;11(6):e200313.