# Treatment options for severe myasthenia gravis
Severe myasthenia gravis typically requires a combination of treatments. The choice depends on how the disease presents, which antibodies are present, whether there is a thymoma, and how well the patient responds to initial therapies. The main treatment groups are described below.
Symptomatic treatment
Cholinesterase inhibitors
ProveniIncluded in official guidelines, or approved by EMA or FDA
These medications increase the level of acetylcholine in the muscles by slowing down the breakdown process. In this way, signals between nerves and muscles can be transmitted better. They work quickly (within minutes to hours) and help against tired muscles and drooping eyelids.
Side effects are usually mild and reversible: stomach pain, nausea, increased saliva and tear production. In rare cases, overdosing can lead to confusing symptoms. These medications only provide symptom relief and do not stop the underlying immune process.
Immunosuppressants
ProveniIncluded in official guidelines, or approved by EMA or FDA
These agents suppress the immune system so that the body produces fewer antibodies that attack the neuromuscular junction. They often form the basis of long-term treatment and help prevent worsening and make remission possible.
Commonly used substances work through different mechanisms: some block cell division of immune cells, others suppress certain inflammatory signals. Side effects depend on the specific agent and can include infections, kidney toxicity, liver damage, and increased cancer risk. Therefore, regular monitoring is done through blood tests.
Rapid stabilization in severe phases
Plasma exchange (plasmapheresis)
ProveniIncluded in official guidelines, or approved by EMA or FDA
This technique removes harmful antibodies directly from the blood. Blood is drawn from the body, and its plasma (the liquid part containing antibodies) is replaced with donor plasma or artificial fluid. This can have an effect within days to weeks.
Plasma exchange is mainly used for severe flares (crisis) or in preparation for surgery. Side effects are usually minor but can include hypocalcemia (low calcium), infections, and blood clotting problems. The effect is usually temporary, so it must be followed by long-term therapy.
Intravenous immunoglobulin (IVIG)
ProveniIncluded in official guidelines, or approved by EMA or FDA
These are antibodies from healthy donor blood that suppress the body's own immune system and reduce inflammation. The mechanism is not yet fully understood, but it works through various routes: it can neutralize harmful antibodies, inhibit the complement system, and better regulate certain immune cells.
IVIG works more slowly than plasma exchange (days to weeks) but the effect lasts longer. Possible side effects include headache, fever, thrombosis (blood clots), kidney failure, and in rare cases heart rhythm disturbances. Patients with certain conditions such as IgA deficiency must be treated carefully.
Complement-targeting therapies
Eculizumab
ProveniIncluded in official guidelines, or approved by EMA or FDA
This medication blocks complement C5, an important component of the immune system involved in attacking the neuromuscular junction. By inhibiting complement, it reduces inflammation and damage to the muscles.
Eculizumab can be used in anti-acetylcholinesterase receptor (AChR) antibody-positive patients, especially when they respond inadequately to immunosuppressants. Side effects can include infections (especially meningococcal bacteria), infusion reactions, headache, and abdominal pain. Patients must be vaccinated against certain bacteria.
Povetacicept
ResearchediPositive results in clinical studies, not yet standard treatment
This agent blocks complement C1s, early in the complement cascade. In ongoing studies, it shows promising results, especially in generalized myasthenia gravis. The mechanism of action differs from C5 blockade and may be more effective in certain patient groups.
Side effects are not yet fully characterized, but initial data suggest similarity with other complement inhibitors. This medication is not yet standard available.
FcRn receptor inhibitors
Efgartigimod
ProveniIncluded in official guidelines, or approved by EMA or FDA
This medicine blocks the FcRn receptor that is responsible for the reuse of harmful antibodies in the body. By blocking this, the body breaks down these antibodies more quickly. So it doesn't work by directly suppressing the immune system, but by disrupting the natural recycling mechanism of antibodies.
Efgartigimod can be used for anti-AChR-antibody–positive generalized myasthenia and for certain severe forms. It can have an effect within just a few days. Side effects are generally mild: infections (due to lowered immunity), infusion reactions, fatigue and headaches. The medicine is given intravenously.
Treatment approaches in development
Aritinercept
ResearchediPositive results in clinical studies, not yet standard treatment
This medicine binds to BAFF (B-cell activating factor), a signal that activates B cells to produce antibodies. By blocking BAFF, B cells become less active and less antibody production occurs.
This medicine is currently being investigated in clinical studies. Preliminary data suggest usefulness in generalized myasthenia, especially in combination with other therapies. Many side effects are not yet well documented.
CC-97540
ResearchediPositive results in clinical studies, not yet standard treatment
This experimental medicine works on various immune cells at the same time and is being investigated for difficult-to-treat myasthenia gravis. It still needs further research.
Surgical treatment
Thymectomy (removal of the thymus)
ProveniIncluded in official guidelines, or approved by EMA or FDA
The thymus is a gland in the chest that plays a role in the development of myasthenia gravis. Removing it can cause remission or significantly reduce symptoms, especially in younger patients and those with a thymoma.
The operation can be performed openly (large incision) or minimally invasively (small opening). Side effects are those of any operation: infection, bleeding, pain. Long-term effects are still being investigated; recent studies show positive long-term outcomes. Thymectomy is especially effective in the first years after diagnosis.
Treatment of myasthenic crisis
In severe worsening with breathing difficulties or swallowing problems, rapid action is taken with more intensive therapies:
- Plasmapheresis and IVIG can be deployed quickly one after another or simultaneously
- Mechanical ventilation (artificial breathing) may be necessary
- Intensive immunosuppressants are started or increased
- Nutritional support via feeding tube may be necessary
Role of corticosteroids
ProveniIncluded in official guidelines, or approved by EMA or FDA
Corticosteroids work broadly immunosuppressant and can have an effect fairly quickly. They are used especially in acute situations and as bridge therapy, until slower-acting medicines (such as immunosuppressants) take effect.
Long-term use of high doses of corticosteroids brings significant side effects: weight gain, bone loss, infections, mood changes. For this reason, attempts are made to keep the dose low and to gradually reduce it.
Treatment strategy in severe forms
In severe generalized myasthenia gravis, treatment is usually stratified:
1. **Initial**: symptomatic cholinesterase inhibitors + corticosteroids or IVIG for rapid stabilization
2. **Follow-up**: slow-acting immunosuppressants (usually combined) as the basis
3. **Further options**: complement-targeting (eculizumab) or FcRn inhibition (efgartigimod) if response is insufficient
4. **Surgery**: thymectomy is considered, especially early in the course of the disease
The combination of multiple mechanisms of action proves more effective than monotherapy. Regular evaluation determines whether dosing needs to be adjusted or other medicines are needed.
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_This information never replaces a doctor's judgment. Always discuss your situation with your own healthcare provider._