Introduction
GL/ULT-g/0019 January 2025
A patient with highly active generalized myasthenia gravis (gMG) despite multiple immunosuppressants
History of Present Illness
Welcome. Your patient today is Sabrina T.
Sabrina has a history of highly active generalized myasthenia gravis (gMG), which has persisted despite multiple prior immunosuppressive therapies.
Medical History
Sabrina is a 35-year-old female with a history of generalized myasthenia gravis (gMG) who initially presented with partial right-sided ptosis and intermittent horizontal diplopia. Over time, she developed progressive symptoms, including generalized muscle weakness, fatigue, worsening ptosis, and intermittent dysphagia, which significantly impacted her daily activities and ability to work. A diagnosis of gMG was confirmed, and initial treatment included prednisone 30 mg/day and pyridostigmine 240 mg/day.
Symptom exacerbations prompted adjustments in her treatment regimen. Subsequently, the patient stabilized but continued to report muscle weakness and fatigue, though improvements in respiratory function and swallowing were noted.
The patient recently experienced a myasthenic exacerbation, presenting with dyspnea, generalized weakness, dysarthria, and severe dysphagia with difficulty managing oral secretions. She was hospitalized in the ICU due to respiratory compromise requiring noninvasive ventilation. To manage the exacerbation, she underwent intravenous immunoglobulin (IVIG) therapy. This treatment led to significant clinical improvement, including resolution of respiratory distress and gradual recovery of muscle strength. The patient was transitioned out of the ICU and began physical therapy for rehabilitation, focusing on restoring functional mobility and addressing residual bulbar symptoms.
However, the patient has now returned to your office following her recent myasthenic crisis. She reports mild worsening of bulbar symptoms and occasional shortness of breath. Her symptoms improve with rest, indicating a stable condition.
Past surgical history: none.
Current medications: prednisone 40 mg/day and mycophenolate mofetil 3 g/day.
Allergies: None.
Review of systems: review of systems is normal today.
Family and Social History
Sabrina is married and lives with her husband and two young daughters. Her mother has a history of rheumatoid arthritis, and her father has hypertension. Sabrina works as a teacher but has reduced her hours due to health-related fatigue. She does not smoke or use recreational drugs. She occasionally drinks a glass of wine socially but does not consume alcohol regularly.
Physical Examination Notes
GENERAL: well-developed; appears fatigued but in no acute distress; alert and oriented x 3. She reports worsening fatigue with sustained activity.
HEAD, EYES, EARS, NOSE, AND THROAT: pupils equal, round, reactive to light, and accommodation; moderate bilateral ptosis noted, partially obscuring vision; extraocular motion intact but shows significant fatigability, with symptoms worsening upon prolonged gaze; moist mucosa without lesions; reports intermittent double vision (diplopia).
NECK: full range of motion; normal pulses; smooth, normal-sized thyroid; no lymphadenopathy.
HEART: normal rate and rhythm; normal S1 and S2; no murmurs, gallops, or rubs.
LUNGS: clear to auscultation and percussion; no wheezing or crackles; no accessory muscle use observed; respiratory effort appears normal.
ABDOMEN: soft, nontender; normal bowel sounds; no hepatomegaly, splenomegaly, or ascites.
EXTREMITIES: no clubbing, cyanosis, or edema; pulses intact bilaterally.
NEUROLOGIC: cranial nerves II-XII intact; noted ptosis with bilateral extraocular muscle weakness; demonstrates mild neck flexor weakness; mild proximal muscle weakness in upper and lower extremities, which worsens with repetitive testing; sensory and cerebellar function intact; deep tendon reflexes 2+ symmetric.
SKIN: warm to the touch; thin skin with mild bruising consistent with steroid use; mild facial rounding (cushingoid features).
MUSCULOSKELETAL: mild proximal muscle weakness in both upper and lower extremities with noted fatigability upon repeated testing.
Consultation
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Transcript · How have things been?
I’m struggling with how the steroids are affecting me. My face is so puffy, and I’ve gained weight. I barely recognize myself. I’d like to stop using them if possible.
I understand, Sabrina. The side effects of steroids can be tough. There are new strategies, and we’ll explore them during our visit today.
Transcript · How do you feel about your medications and treatment?
Honestly, Doctor, it’s been a struggle. I’m grateful for the progress I’ve made, but it’s hard to feel like myself when I’m always tied up with the frequent treatments. I have so much going on—work, family, the kids’ activities. I feel like my life is centered around my illness, and that’s tough. I’d also like to be able to return to work.
I hear you, and it’s completely understandable to want more balance and flexibility. We’ll keep this in mind when evaluating your alternative options.
Transcript · Have you considered the thymectomy?
In the past, we spoke about a thymectomy. In some cases, removing the thymus can help lessen the immune system’s attack on the body, which can reduce symptoms over time and decrease the need for medication. It’s one of the options we consider.
I understand, but surgery makes me nervous—the thought of possible complications, pain, and recovery time. I’m worried about the risks involved. I did see the surgeon as you requested, but when she explained the procedure to me, I was not interested.
I understand, Sabrina. Surgery is a big decision, and it’s natural to be concerned about the risks and recovery. We want to be sure any approach fits your comfort level and long-term goals. So, we’ll take surgery off the table.
Transcript · Which symptoms are impacting your well-being the most?
It’s been especially hard whenever we try to cut down on the steroids. I can’t work like I used to, and that’s putting a lot of stress on me and my family. Plus, I’ve been dealing with double vision, droopy eyelids, and trouble swallowing. Those make even everyday things really tough.
That sounds frustrating. Thank you for sharing that with me—it really helps us figure out how to make this more manageable for you. Let’s look into some other options that could reduce the need for steroids and help you feel more in control.
Tests
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Myasthenia Gravis Activities of Daily Living (MG-ADL) scale
Myasthenia Gravis Foundation of America (MGFA) Clinical Classification
Myasthenia Gravis Quality of Life 15-item Revised (MG-QoL15r) questionnaire
Quantitative Myasthenia Gravis (QMG) test
Diagnoses
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Existing Diagnoses
| Name | Start date | End date |
|---|---|---|
| Myasthenia gravis | … | Ongoing |
| Myasthenic crisis | … | … |
| Myasthenic crisis | … | … |
Decisions
Medication selection · non-medication orders.
Existing Prescriptions
Prednisone
Dose: 40 mg · Route: oral · Freq.: qd (1x/day)
Pyridostigmine
Dose: 240 mg · Route: oral · Freq.: qd (1x/day)
Mycophenolate mofetil
Dose: 3 g · Route: oral · Freq.: qd (1x/day)
Rituximab
Dose: 1000 mg · Route: IV · Freq.: every six months
Already discontinued.
Plasmapheresis
Freq.: every other day
Immunoglobulin (IVIG)
Dose: 2 g/kg · Route: Intravenous · Freq.: every day
Medication Selection
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Non-Medication Orders
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Medication adherence
Patient monitoring
Physical activity
Follow-up
Patient education and counseling
Case Review
Sabrina is a 35-year-old female patient with a history of highly active gMG, which has persisted despite multiple prior immunosuppressive therapies.
Sabrina’s journey.
Sabrina expressed a strong desire to reduce or discontinue prednisone due to adverse effects, as well as a need for better disease control.
In cases like Sabrina’s, with refractory AChR-Ab-positive gMG, several treatments could be reasonable options based on recent regulatory approvals.
Highly active gMG
Healthcare professionals are advised to consult their national guidelines and institutional best practices to ensure compliance with local standards of care. The guidelines for the management of myasthenic syndromes for diagnosing and treating myasthenic syndromes recommend distinguishing between mild/moderate and (highly) active disease, including refractory gMG, to ensure tailored and effective treatment strategies.
Disease Classification:
Mild/Moderate gMG:
- Symptoms are less severe and generally manageable with standard therapies.
- Patients may experience fluctuations in symptoms but not frequent or severe exacerbations.
Highly Active (including refractory) gMG:
- Moderate/high MGFA status (≥MGFA IIb) and/or at least two severe exacerbations/myasthenic crises within 1 year despite adequate treatment.
- Persistent symptoms impacting daily living (≥MGFA IIa) with one severe exacerbation/crisis within the past year despite adequate therapy.
- Mild/moderate symptoms (≥MGFA IIa) persisting for over 2 years despite appropriate disease-modifying and symptomatic treatment.
- Includes patients with frequent severe exacerbations or those resistant to standard therapies.
Refractory gMG is defined by persistent symptoms that do not respond sufficiently to disease-modifying and symptomatic therapies and/or a recurring need for intensive treatments to control severe exacerbations or myasthenic crises. 10–15% experience refractory gMG .
Minimal symptom expression (MSE)
The therapeutic goal for gMG is the best possible disease control while preserving or restoring the patient's quality of life. This is known as minimal symptom expression (MSE). MSE represents a higher standard for sustained symptom control. MSE is defined by an MG-ADL score of 0–1, indicating either no symptoms or very minimal ones, providing an objective measure of disease stability. The guidelines for the management of myasthenic syndromes define four levels of disease control:
- Complete disease control without residual symptoms: No disease activity is present, and patients report no residual symptoms.
- Complete disease control with stable minimal residual symptoms: No disease activity is detected, but patients may experience stable, minimal residual symptoms indicative of incomplete remission.
- Incomplete disease control with ongoing disease activity: This state is characterized by instability, deterioration, or fluctuations with residual symptoms and the continuous emergence of new or developing symptoms, which may include fluctuations or crises.
- No disease control with high disease activity: This level includes refractory gMG and is marked by persistent symptoms with or without crises or crisis-like deteriorations, as well as resistance to therapy.
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A patient with highly active generalized myasthenia gravis (gMG) despite multiple immunosuppressants · GL/ULT-g/0019 January 2025 · Sabrina T.
Faculty — R. Andrade MD
Supporter — Alexion, AstraZeneca Rare Disease