Myasthenia gravis is a heterogeneous disease. Clinical presentation, antibody profile, age at onset, thymic pathology, disease activity, and treatment response can all influence management. Recent advances in targeted therapies have expanded treatment options, particularly for patients with generalized MG (gMG) whose symptoms remain inadequately controlled or who experience significant treatment-related adverse effects. [3,4]
Disease Overview
At the neuromuscular junction, a nerve releases acetylcholine (ACh), which binds to receptors on muscle cells and initiates contraction. In MG, autoantibodies target proteins involved in this process, reducing the effectiveness of nerve-to-muscle transmission and causing weakness and fatigue. [1,2]
In the most common form, antibodies target the ACh receptor (AChR) on the muscle, accounting for 80% to 85% of patients. Other patients have antibodies against muscle-specific kinase (MuSK) (5%-8%) or low-density lipoprotein receptor-related protein 4 (LRP4) (<1%). These antibody subtypes differ in their underlying mechanisms and may have distinct clinical features and treatment implications. Some patients have clinically defined MG despite negative results on routine antibody testing. [1,2,4]
Signs and Symptoms
Muscle weakness is typically mildest in the morning after rest and intensifies as the day progresses or with repeated physical effort (such as chewing, speaking, or walking), improving temporarily with rest. A patient might experience ocular symptoms, such drooping of the eyelid (ptosis) and double vision (diplopia); difficulty chewing as a meal progresses; or weakness when climbing stairs. The pattern and severity of weakness vary among patients and can change over time. [1–3]
Patients with MG may present with ocular symptoms only. In some patients, this “ocular” MG remains their primary disorder, whereas others will develop weakness in additional muscle groups.
Eye symptoms
Ptosis may affect one or both eyelids. Weakness of the muscles that move the eyes may cause diplopia. Diplopia may also be associated with difficulty in maintaining eye alignment or a steady gaze.
Facial weakness, speech issues, and dysphagia
Weakness of facial and bulbar muscles may cause changes in facial expression, slurred or nasal speech, chewing fatigue, difficulty swallowing, or choking during meals. Bulbar symptoms can affect nutrition, communication, and airway safety. [3]
Neck, arms, and legs
Myasthenia gravis may cause weakness in the neck, shoulders, arms, hips, and legs. Patients may have difficulty holding up their head, lifting objects, rising from a chair, climbing stairs, or walking longer distances. [2,5]
Breathing difficulties
Patients with MG can experience weakness affecting the respiratory muscles. Severe weakness can cause a myasthenic crisis, a medical emergency that may require intensive care and ventilatory support. New or rapidly worsening breathing difficulties, or severe swallowing problems, require urgent medical assessment. [3,5,6]
Causes
AChR antibody–positive MG
AChR antibodies can reduce the number of functional ACh receptors, accelerate receptor breakdown, and activate the complement system. Complement-mediated injury damages the postsynaptic membrane and impairs neuromuscular transmission. This mechanism provides the rationale for complement-inhibiting treatments in appropriately selected patients.[8]
MuSK antibody–positive MG
MuSK is important for organizing and maintaining ACh receptors at the neuromuscular junction. MuSK antibodies generally act through a different mechanism from AChR antibodies and do not activate complement in the same way. MuSK-associated MG can feature prominent facial, bulbar, and respiratory weakness, and treatment considerations may differ from those for AChR-positive disease. B-cell-directed therapy may play an important role in the treatment of these patients. [4]
LRP4 antibodies and seronegative MG
LRP4 is involved in the signaling pathway that helps organize ACh receptors. A smaller proportion of patients have LRP4 antibodies. Others test negative for antibodies included in routine testing. Seronegative MG is not necessarily a single biological entity; interpretation depends on the clinical presentation, the tests performed, and their sensitivity. Antibody results alone do not fully predict an individual’s disease course or response to treatment. [9]
Types of Myasthenia Gravis
Myasthenia gravis can be classified in several complementary ways.
Ocular MG: Weakness is limited to the muscles controlling the eyes and eyelids.
Generalized MG: Weakness extends beyond the eyes and may affect bulbar, neck, limb, or respiratory muscles.
AChR-positive MG: Often involves complement-mediated injury and includes patients who may be candidates for complement inhibitors.
MuSK-positive MG: Has a distinct antibody mechanism and may require a different treatment approach.
LRP4-positive or seronegative MG: Requires interpretation of laboratory findings alongside clinical and electrodiagnostic evidence.
In addition to the classifications of ocular, generalized, AChR-positive, MuSK-positive, and LRP4-positive or seronegative MG, age at onset and thymic pathology are also relevant. AChR-positive disease can be associated with thymic hyperplasia or thymoma, and the presence of thymoma has important implications for management. These classifications also help to inform treatment decisions, but more information is necessary before deciding a course of therapy. For instance, the patient’s current disease activity, any functional limitations, and existing comorbidities can alter the treatment decision. Furthermore, the patient’s treatment history and individual preferences also matter. [3,4]
Diagnosis
Diagnosis is based on the clinical presentation, supported by laboratory and neurophysiological testing. Because symptoms fluctuate and can resemble those of other disorders, evaluation may require more than one test. The differential diagnosis might include amyloid lateral sclerosis, congenital myasthenia syndrome, and myositis. [1,3,4]
Antibody testing
Blood testing commonly evaluates AChR and MuSK antibodies. Additional testing, including LRP4 antibodies or more sensitive assays in selected cases, may be considered when initial results are negative but clinical suspicion remains. A negative antibody test does not by itself exclude MG. [4]
Neurophysiological testing
Repetitive nerve stimulation measures muscle responses to repeated nerve stimulation; a decremental response may support the diagnosis of a neuromuscular transmission disorder.
Single-fiber electromyography (EMG) assesses variability in neuromuscular transmission and can detect abnormalities associated with MG. [4]
Thymic imaging
The initial assessment must include chest imaging to evaluate the thymus for thymoma. Further investigations may be needed to evaluate alternative diagnoses or coexisting conditions. [10]
Treatment and Management
The goals of treatment are multifaceted. The key goals are to improve muscle function, control autoimmune disease activity, prevent exacerbations, reduce treatment-related adverse effects, and support daily functioning. To address these objectives, treatment may need to be multifaceted as well. Options include:
- Symptomatic medication
- Conventional immunotherapy
- Thymectomy
- Rapid-acting therapies for significant worsening or myasthenic crisis
- Targeted biologic treatments
Ptosis and ophthalmoparesis that limit a patient’s ability to function might improve with immunosuppressant agents if anticholinesterase agents have not been effective. [3] Studies of subgroups of patients with MG treated with rituximab have shown significant improvement in manual muscle testing (MMT). Thymectomy is recommended if chest imaging shows a patient with MG has a thymoma or thymic enlargement. Some were able to reduce their prednisone dose post-thymectomy. [3–5]
Treatment decisions depend on antibody status, symptom distribution and severity, the speed of control needed, prior treatment response, comorbidities, safety considerations, access, treatment burden, and patient preferences.
Assessing disease activity and treatment goals
Management is guided not only by whether MG is ocular or generalized, but also by current disease activity and the impact of symptoms on daily life. Persistent functional limitations, recurrent significant exacerbations, difficulty reducing corticosteroid dose, or inadequate control despite appropriate therapy may prompt reassessment and consideration of treatment escalation. One issue is that definitions of “high disease activity” and “treatment-refractory MG” may vary. For example, MG can be stratified into mild-to-moderate versus high disease activity (including treatment-refractory status), based on autoantibody activity, thymic pathology, and the presence of clinical manifestations. [4]
Treatment goals extend beyond improvement at a single point in time. They include sustained symptom control, improved daily functioning, prevention of exacerbations, and minimizing long-term treatment burden—particularly corticosteroid exposure. The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale can help track the impact of symptoms on everyday activities. The Quantitative Myasthenia Gravis (QMG) score provides a more clinician-assessed measure of disease severity. These measures support, but do not replace, clinical judgment and discussion with the patient. [4]
Symptomatic treatment
Pyridostigmine is an acetylcholinesterase inhibitor that increases the availability of ACh at the neuromuscular junction. It can improve muscle function but does not directly suppress the autoimmune process. Effectiveness and tolerability vary. Clinical experience has not supported that patients consistently improve or tolerate the treatment well. Adverse effects can include abdominal cramping, diarrhea, sweating, and increased secretions; it may be less effective or poorly tolerated in some patients with MuSK-positive MG. [1,3]
Conventional immunotherapy
Corticosteroids and other immunosuppressive medicines reduce abnormal immune activity. Treatment may include prednisone and steroid-sparing agents, such as azathioprine, mycophenolate mofetil, tacrolimus, or cyclosporine. [1,3]
These medicines differ in their time to benefit, evidence base, monitoring requirements, and adverse-effect profiles. Some steroid-sparing agents may take months to provide their full effect, while prolonged corticosteroid use can cause substantial adverse effects. Clinicians seek effective disease control while reducing corticosteroid exposure to the lowest practical dose. Initiation, dose changes, and tapering require clinical supervision because symptoms can temporarily worsen in some circumstances. [3,4]
Rapid-acting treatments
Intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) may be used when rapid improvement is needed, including in selected severe exacerbations, myasthenic crisis, or around certain procedures. They may also serve as a bridge until longer-term therapies take effect. [3,4]
Thymectomy
Thymectomy is indicated when thymoma is present and may benefit selected patients with non-thymomatous, AChR-positive gMG. Evidence supports benefit in patients with thymoma, but expected outcomes depend on clinical characteristics and the timing of surgery. The decision should be made with the neurology and surgical teams, considering the patient’s disease profile and overall health. [3,4,10,11]
Targeted therapies: selection and practical considerations
Targeted therapies act on specific components of the immune response. The availability of targeted treatments, such as complement inhibitors, neonatal Fc receptor (FcRn) inhibitors, and B-cell directed therapy, has expanded therapeutic options for patients with gMG who have persistent symptoms, significant disease activity, or difficulty achieving satisfactory control with conventional treatment. They are not interchangeable, and there are limited direct head-to-head comparisons. Selection should consider the patient’s antibody subtype, disease activity, prior response, safety profile, dosing preferences, and access. [4,5,7]
Complement inhibitors
Complement inhibitors reduce activity in the complement pathway, which contributes to neuromuscular junction injury in AChR-positive MG. Examples include eculizumab, ravulizumab, and zilucoplan. These agents differ in administration and dosing schedule. Eculizumab, for example, is administered every two weeks by intravenous infusion by a healthcare professional, while ravulizumab is given by intravenous infusion approximately 6 to 7 times a year. In contrast, zilucoplan can be delivered subcutaneously once daily by prefilled syringe or autoinjector by the patient or caregiver at home. [16-18] This range of administration and dosing schedules can give patients a choice that works with their individual lifestyles.
Complement inhibition is associated with an increased risk of serious meningococcal infection. Vaccination and other risk-mitigation measures specified in the product labeling are essential; urgent treatment circumstances require following the relevant prescribing information and clinical protocols.
Neonatal Fc receptor (FcRn) inhibitors
FcRn inhibitors reduce circulating immunoglobulin G (IgG), including disease-associated antibodies. Options include efgartigimod, rozanolixizumab, and nipocalimab. Their approved populations, administration schedules, treatment cycles, and safety considerations differ by product and formulation.[5-7,12,14,15]
B-cell-directed therapy
B-cell-directed treatments target immune cells involved in antibody production. Rituximab has been used off-label in selected patients, particularly in MuSK-positive or difficult-to-control MG. Inebilizumab, a CD19-directed therapy, is FDA-approved for adults with AChR- or MuSK-antibody-positive gMG. Product-specific screening, vaccination, infection, and monitoring requirements should be reviewed before treatment. For example, inebilizumab should not be utilized in patients with active hepatitis B infection, and other products may increase the risk of infection. [6–9,13]
Factors affecting choice of targeted treatment
Antibody subtype can help identify relevant treatment mechanisms and thus guide targeted treatment choice, but it does not determine the best therapy for every patient. Other considerations include: [4]
Disease activity and urgency: Persistent disability or recurrent severe exacerbations may support escalation.
Expected response: Therapies differ in their onset and pattern of benefit.
Safety and prevention: Infection risk, vaccination requirements, laboratory monitoring, and comorbidities can affect suitability.
Administration and treatment burden: Intravenous infusions, subcutaneous injections, daily administration, and intermittent treatment cycles place different demands on patients.
Cost and access: Insurance type, and pharmaceutical coverage and out-of-pocket costs can limit patient access and choices.
For many patients, targeted biologics are used as add-on therapy alongside conventional treatment. Whether and when to taper other medicines, switch mechanisms, or discontinue treatment remains individualized decisions. Evidence is still evolving regarding the optimal sequence, duration, and predictors of response. That is, guidance is lacking on the efficacy and safety of any particular protocol involving sequential use (or combination use) of targeted therapies. [4,5]
Current U.S. treatment landscape
The following summary reflects U.S. indications as of October 2026, based on the prescribing information for each product. It is not a substitute for current prescribing information.
| Treatment | Broad U.S. indication relevant to MG |
| Eculizumab (Soliris) | gMG in AChR-positive patients; current labeling includes adults and eligible pediatric patients |
| Ravulizumab (Ultomiris) | Adult AChR-positive gMG |
| Zilucoplan (Zilbrysq) | Adult AChR-positive gMG |
| Efgartigimod alfa-fcab (Vyvgart, IV formulation) | Adult gMG; see current label for the formulation-specific indication |
| Rozanolixizumab (Rystiggo) | Adult AChR- or MuSK-positive gMG |
| Nipocalimab (Imaavy) | AChR- or MuSK-positive gMG in patients aged 12 years and older |
| Inebilizumab (Uplizna) | Adult AChR- or MuSK-positive generalized MG |
This table summarizes indications rather than ranking treatments or recommending one agent over another. Indications and precautions can change; clinicians should confirm the latest FDA-approved labeling before prescribing. [12-18]
Emerging Treatments: Cemdisiran and the NIMBLE Trial
Cemdisiran is an investigational complement inhibitor, specifically a small interfering RNA (siRNA) therapy designed to reduce production of complement component C5 in the liver. By lowering C5, it aims to limit complement-mediated injury associated with AChR-positive gMG. [19]
In the Phase 3 NIMBLE trial, cemdisiran was studied in adults with gMG, including AChR- and LRP4-antibody-positive participants. The published trial reported significant improvement in MG-ADL scores at 24 weeks compared with placebo. Cemdisiran was administered by subcutaneous injection every 12 weeks. These results support continued evaluation of the treatment, but they do not establish superiority over other MG therapies. [19,20]
Other research approaches include additional B-cell- and plasma-cell-directed therapies, cellular therapies, and strategies designed to restore immune tolerance. These remain areas of investigation; they should not be presented as established treatment options unless supported by the relevant evidence and regulatory status. [4,5]
Living With Myasthenia Gravis
Overall, the care of patients with MG should be multidisciplinary and coordinated across relevant specialties (e.g., neurology, ophthalmology, physical therapy). Pregnancy planning, surgery, vaccination, and management of other medical conditions may require specific discussion with the greater treating team.[3]
Clinical Research and the Future of Treatment
The treatment of MG is becoming more individualized, as clinical trials and real-world studies expand the evidence for targeted therapies.[21] Important questions remain:
- Which patients are most likely to benefit from a given treatment?
- When should targeted therapies be introduced?
- How should treatments be sequenced or switched?
- How long should therapy continue?
- Can durable remission can be achieved?.
More direct comparisons between therapies and validated predictors of response are needed.[4,5]
CheckRare’s MG interviews and educational programs can provide additional perspectives on current research, expert interpretation, and the experiences of people living with the disease.
Resources
- Myasthenia Gravis Foundation of America (MGFA): Patient and clinician resources, treatment information, and support.
- International consensus guidance and professional guidelines: Evidence-informed recommendations for MG management.
- ClinicalTrials.gov: Registry of clinical studies, including ongoing MG trials.
- CheckRare: Additional MG interviews, research updates, and educational content.
This overview is intended for educational purposes and does not replace individualized medical advice. Diagnosis and treatment decisions should be made with a qualified healthcare professional familiar with the patient’s clinical history.
References
- Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375:2570–2581. doi:10.1056/NEJMra1602678.
- Tannemaat MR, Huijbers MG, Verschuuren JJGM. Myasthenia gravis—pathophysiology, diagnosis, and treatment. Handb Clin Neurol. 2024;200:283–305. doi:10.1016/B978-0-12-823912-4.00026-8. https://pubmed.ncbi.nlm.nih.gov/38494283/
- Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114–122. doi:10.1212/WNL.0000000000011124.
- Gerischer L, Doksani P, Hoffmann S, Meisel A. New and emerging biological therapies for myasthenia gravis: a focused review for clinical decision-making. BioDrugs. 2025;39:185–213. doi:10.1007/s40259-024-00701-1.
- Barnett-Tapia C, Cortés Vicente E, Pascuzzi RM, et al. Measuring the effect of rozanolixizumab using the Myasthenia Gravis Impairment Index: analyses from the randomized phase 3 MycarinG study. J Neurol. 2025;272(1):752. doi:10.1007/s00415-025-13480-8
- Howard JF Jr, Vu T, Li G, et al. Subcutaneous efgartigimod PH20 in generalized myasthenia gravis: A phase 3 randomized noninferiority study (ADAPT-SC) and interim analyses of a long-term open-label extension study (ADAPT-SC+). Neurotherapeutics. 2024;21(4):e00378. doi:10.1016/j.neurot.2024.e00378
- Menon D, Bhandari V. FcRn inhibitors in the context of myasthenia gravis. Expert Opin Emerg Drugs. 2025Jan 28:1-4 Published online January 28, 2025. doi:10.1080/14728214.2025.245806
- Wang Y, Nao J, Duan Y, Li Z, Feng J. Therapeutic strategies targeting complement in myasthenia gravis patients. J Neurol. 2025;272(8):489. doi:10.1007/s00415-025-13225-7
9. Gligora I, Businaro P, Serra L, et al. Low prevalence and inconsistency of LRP4-IgG detection in suspected myasthenia gravis: a multicenter CBA comparison. Neurol Neuroimmunol Neuroinflamm. 2026;13(3):e200554.
- Claytor B, Delasos L, Raymond DP, et al. Myasthenia gravis and thymoma. Muscle Nerve. 2026;74:1156-1173. doi: 10.1002/mus.70318
- Rossini E, Leonardi L, Morino S, Antonini G, Fionda L. Immunological targets in generalized myasthenia gravis treatment: where are we going now? Brain Sci.. 2025;15(9):978. doi:10.3390/brainsci15090978
- IMAAVY (nipocalimab-aahu) prescribing information. Johnson & Johnson. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/IMAAVY-pi.pdf
- UPLIZNA (inebilizumab-cdon) prescribing information. Amgen. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/uplizna/uplizna_fpi_english.pdf
- VYVGART (efgartigimod alfa-fcab) prescribing information. Argenx. https://argenx.com/content/dam/argenx-corp/products/vyvgart-hytrulo-prescribing-information.pdf
- RYSTIGGO (rozanolixizumab-noli) prescribing information. UCB. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761286s007lbl.pdf
- ZILBRYSQ (zilucoplan) prescribing information. UCB. https://www.ucb-usa.com/zilbrysq-prescribing-information.pdf
- ULTOMIRIS: (ravulizumab) prescribing information. Alexion. https://ultomiris.com/gmg/-/media/alexion_global/documents/regulatory/north-america/usa/2026/english/ultomiris_uspi.pdf?rev=ddc99ca53352428a8164098298aba7f2
- SOLIRIS (eculizumab) prescribing information. AstraZeneca. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebcd67fa-b4d1-4a22-b33d-ee8bf6b9c722
- Vu T, Habib AA, Jacob S, et al. Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;407(10540):1712–1725. doi:10.1016/S0140-6736(26)00690-2.
- Regeneron Pharmaceuticals, Inc. Cemdisiran regulatory submissions accepted for review by FDA and EMA for the treatment of generalized myasthenia gravis (gMG). June 22, 2026. Company regulatory announcement. https://investor.regeneron.com/news-releases/news-release-details/cemdisiran-regulatory-submissions-accepted-review-fda-and-ema
- Myasthenia Gravis Foundation of America. Myasthenia Gravis Treatments Chart. Current treatment and indication overview; consult product labels for prescribing decisions. https://myasthenia.org/myasthenia-gravis-treatments-chart/
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