Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

myasthenic crisis

1st line – intubation and mechanical ventilation

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ACUTE
|
myasthenic crisis
1st line – 

intubation and mechanical ventilation

Indications for mechanical ventilation are forced vital capacity (FVC) 15 mL/kg or less (normal ≥60 mL/kg) and/or negative inspiratory force (NIF) 20 cm H₂O or less (normal ≥70 cm H₂O). Some patients may require a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube.[23]

Initial therapy consists of optimized ventilatory settings to facilitate respiratory muscle relaxation and removal of provoking factor(s).

Plus – plasma exchange or intravenous immune globulin

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ACUTE
|
myasthenic crisis
Plus – 

plasma exchange or intravenous immune globulin

Treatment recommended for ALL patients in selected patient group

Acute therapy for the recovery of transmission across the neuromuscular junction with either immune globulin or plasma exchange is required.

Plasma exchange elicits a rapid response, with onset usually after 2 to 3 sessions; however, effects are temporary, lasting weeks.[81][119][122] 

Intravenous immune globulin (IVIG) is easy to administer.[118][119][120][121] When patients respond, onset is within 4 to 5 days, with maximal response apparent within 1 to 2 weeks; however, its effects are also temporary.

In patients with muscle-specific tyrosine kinase (MuSK) MG, plasma exchange or IVIG may be used during acute exacerbations and crises, but IVIG appears to be less effective than plasma exchange in this subpopulation.[1][50]

Primary options

immune globulin (human): 1000 mg/kg intravenously once daily for 1-2 days

Plus – supportive care

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ACUTE
|
myasthenic crisis
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care includes deep venous thrombosis prophylaxis; ulcer prophylaxis; adequate nutrition and hydration; and avoidance of infections and drugs that may worsen myasthenia symptoms.

Consider – corticosteroid

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ACUTE
|
myasthenic crisis
Consider – 

corticosteroid

Treatment recommended for SOME patients in selected patient group

High-dose corticosteroids may be initiated concurrently with intravenous immune globulin (IVIG) or plasma exchange, as they reach their maximal effectiveness at the time when the effects of IVIG and plasma exchange are waning.[131][132] Once the patient has begun to show maximal improvement, the dose can be slowly decreased. Premature and/or rapid taper of corticosteroids often results in exacerbation of symptoms.

Primary options

prednisone: 1 to 1.5 mg/kg orally once daily

ONGOING

mild to moderate disease (class I to III)

1st line – pyridostigmine

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ONGOING
|
mild to moderate disease (class I to III)
1st line – 

pyridostigmine

Patients with mild and occasional symptoms require no treatment.

The cholinesterase inhibitor pyridostigmine is part of initial treatment for most patients with either ocular or generalized MG, with the dose depending on severity of symptoms.[1][3][89][90][91] However, patients with antibodies to muscle-specific tyrosine kinase (MuSK) often respond poorly to cholinesterase inhibitors, with frequent adverse effects, and occasional worsening of symptoms.[1]

Muscarinic adverse effects can often be decreased by giving pyridostigmine in combination with glycopyrrolate. Alternatively, loperamide may prove useful for persistent diarrhea when the dose of pyridostigmine cannot be reduced.

Taking pyridostigmine 30 minutes prior to eating with a small amount of food is helpful for patients with oral, facial, buccal, pharyngeal, and/or lingual dysfunction. The sustained-release formulation of pyridostigmine may be used for nighttime dosing in patients needing treatment during the night or who have difficulty with the first morning dose of pyridostigmine. It should rarely, if ever, be used for daytime dosing because of variability in absorption.

Primary options

pyridostigmine: dose is highly individualized; consult specialist for guidance on dose

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Consider – corticosteroid

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ONGOING
|
mild to moderate disease (class I to III)
Consider – 

corticosteroid

Treatment recommended for SOME patients in selected patient group

A corticosteroid (e.g., prednisone) is used for patients in whom pyridostigmine monotherapy is not effective.[1][90][91][92][93]

Therapy is started with a low dose and gradually titrated up toward maximum dose. Results from one small randomized controlled trial suggest that low-dose prednisone with gradual escalation may be effective in treating ocular MG and may avoid the adverse effects associated with higher doses of corticosteroids.[94] Some patients may experience worsening of MG, including the risk of precipitating myasthenic crisis, if corticosteroids are started at high dose.[91]

Once treatment goals are achieved, the dose should be tapered to establish a minimally effective dose.[1] One study concluded that rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome in patients with moderate to severe MG.[95]

Patients with generalized MG with moderate symptoms usually require chronic corticosteroid maintenance therapy or additional therapy.[1][90][93]

Primary options

prednisone: 15-20 mg orally once daily initially, increase by 5 mg/day increments every 2-3 days according to response, maximum 60 mg/day

More

Consider – immunosuppressant

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ONGOING
|
mild to moderate disease (class I to III)
Consider – 

immunosuppressant

Treatment recommended for SOME patients in selected patient group

For patients in whom corticosteroids are contraindicated and for patients requiring high doses of corticosteroids, other immunosuppressants may be considered. These other immunosuppressants may be used instead of a corticosteroid, or in combination in order to allow dose reduction (i.e., as a corticosteroid-sparing agent).[1]

Azathioprine is recommended as the first-line immunosuppressive treatment for MG, based on effectiveness and tolerability.[1][90][91][96] Testing for mutations in the gene for thiopurine methyltransferase (TPMT) has been suggested before starting treatment with azathioprine, although mutations causing severe decreases or absence of the enzyme are rare.[140][141] Monitoring blood counts for safety as well as for increase in red cell mean corpuscular volume or induction of mild lymphopenia for establishing a therapeutic response has been suggested.

Other immunosuppressive agents that may be considered include cyclosporine, tacrolimus, mycophenolate, and methotrexate.[1][3][90][97] Cyclosporine is effective, but use is limited due to potential serious adverse effects and drug interactions.[1] Tacrolimus also provides benefit, but is less widely used for MG outside Asia.[98] Evidence for the effectiveness of mycophenolate is equivocal, and randomized controlled trial evidence for methotrexate is lacking; these options may be considered if other options are not tolerated or ineffective.[1][3][90][97][99][100] Mycophenolate and methotrexate are contraindicated in pregnancy.

Primary options

azathioprine: 50 mg orally once daily initially for 1 week, increase gradually according to response, maximum 2-3 mg/kg/day

Secondary options

cyclosporine non-modified: 2.5 mg/kg orally twice daily initially, increase gradually according to response and serum cyclosporine levels

OR

tacrolimus: consult specialist for guidance on dose

Tertiary options

mycophenolate mofetil: consult specialist for guidance on dose

OR

methotrexate: consult specialist for guidance on dose

Consider – rituximab

Back
ONGOING
|
mild to moderate disease (class I to III)
Consider – 

rituximab

Treatment recommended for SOME patients in selected patient group

Evidence suggests that rituximab is effective in patients with muscle-specific tyrosine kinase (MuSK)-MG. It should be considered as an early therapeutic option for patients with moderate MuSK-MG if the response to initial immunotherapy is inadequate.[3][101][102] Some patients may be able to taper and stop prednisone and/or other immunosuppressant agents when on rituximab.

Primary options

rituximab: consult specialist for guidance on dose

Consider – thymectomy

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ONGOING
|
mild to moderate disease (class I to III)
Consider – 

thymectomy

Treatment recommended for SOME patients in selected patient group

Thymectomy has been found to be effective in patients without thymoma who have mild or moderate generalized MG with acetylcholine receptor (AChR) antibodies.[3][90][103][104][105] Thymectomy may be considered early in the disease course for patients ages 18 to 50 years, to minimize the need for immunosuppressants, including long-term corticosteroid treatment.

Patients with ocular AChR-MG with an insufficient response to cholinesterase inhibitors may be offered thymectomy if they have contraindications to, are refractory to, or prefer not to take immunosuppressive agents, although there is no large prospective randomized controlled trial of thymectomy in this patient population.[3]

Thymectomy may be considered for patients without detectable antibodies if immunosuppressants are ineffective or to minimize side effects.

There is no evidence to support thymectomy in patients with muscle-specific tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4, or agrin antibodies without thymoma.[3]

If a patient has what appears to be thymoma on imaging studies, thymectomy is indicated independent of the type or severity of MG.[1][90]

In patients with mild disease who do not otherwise need corticosteroids or other immunosuppressants, treatment with these agents prior to thymectomy is not necessary. Thymectomy should be undertaken in an institution where the health professionals are experienced in anesthetic care and perioperative management of patients with MG. Techniques available range from robotic-assisted or video-assisted thoracotomy to thoracotomy using a transcervical or median sternotomy approach.[107][108][109][110] Less invasive approaches are reported to be as effective as more aggressive approaches.[107][108][110] It is generally accepted that the more complete the removal of thymus, the higher the rate of remission in MG symptoms. Surgical risks include injury to phrenic or recurrent laryngeal nerves, pleural effusion, pulmonary embolism, wound infection or delayed healing, and later sternal instability.

Risk factors for myasthenic crisis after thymectomy include preoperative history of myasthenic crisis, preoperative MG severity, preoperative bulbar symptoms, and high-dose pyridostigmine use.[111][112] One systematic review concluded that plasma exchange before surgery may reduce the risk of postoperative myasthenic crisis in patients with severe disease but may have little or no effect in patients with mild disease.[113]

severe (class IV or V) or refractory disease

1st line – pyridostigmine

Back
ONGOING
|
severe (class IV or V) or refractory disease
1st line – 

pyridostigmine

The cholinesterase inhibitor pyridostigmine is part of treatment for most patients with MG, with the dose depending on severity of symptoms.[1][3][89][90][91] However, patients with antibodies to muscle-specific tyrosine kinase (MuSK) often respond poorly to cholinesterase inhibitors, with frequent adverse effects, and occasional worsening of symptoms.[1]

Muscarinic adverse effects can often be decreased by giving pyridostigmine in combination with glycopyrrolate. Alternatively, loperamide may prove useful for persistent diarrhea when the dose of pyridostigmine cannot be reduced.

Taking pyridostigmine 30 minutes prior to eating with a small amount of food is helpful for patients with oral, facial, buccal, pharyngeal, and/or lingual dysfunction. The sustained-release formulation of pyridostigmine may be used for nighttime dosing in patients needing treatment during the night or who have difficulty with the first morning dose of pyridostigmine. It should rarely, if ever, be used for daytime dosing because of variability in absorption.

Primary options

pyridostigmine: dose is highly individualized; consult specialist for guidance on dose

More

Consider – corticosteroid

Back
ONGOING
|
severe (class IV or V) or refractory disease
Consider – 

corticosteroid

Treatment recommended for SOME patients in selected patient group

A corticosteroid (e.g., prednisone) may be used alongside pyridostigmine, unless contraindicated.[1][90][91][92][93]

Therapy is started with a low dose and gradually titrated up toward maximum dose. Results from one small randomized controlled trial suggest that low-dose prednisone with gradual escalation may be effective in treating ocular MG and may avoid the adverse effects associated with higher doses of corticosteroids.[94] Some patients may experience worsening of MG, including the risk of precipitating myasthenic crisis, if corticosteroids are started at high dose.[91]

Once treatment goals are achieved, the dose should be tapered to establish a minimally effective dose.[1] One study concluded that rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome in patients with moderate to severe MG.[95]

Patients with generalized MG with moderate to severe symptoms usually require chronic corticosteroid maintenance therapy or additional therapy.[1][90][93]

Primary options

prednisone: 15-20 mg orally once daily initially, increase by 5 mg/day increments every 2-3 days according to response, maximum 60 mg/day

More

Consider – immunosuppressant

Back
ONGOING
|
severe (class IV or V) or refractory disease
Consider – 

immunosuppressant

Treatment recommended for SOME patients in selected patient group

For patients in whom corticosteroids are contraindicated and for patients requiring high doses of corticosteroids, other immunosuppressants may be considered. These other immunosuppressants may be used instead of a corticosteroid, or in combination in order to allow dose reduction (i.e., as a corticosteroid-sparing agent).[1]

Azathioprine is recommended as the first-line immunosuppressive treatment for MG, based on effectiveness and tolerability.[1][90][91][96] Testing for mutations in the gene for thiopurine methyltransferase (TPMT) has been suggested before starting treatment with azathioprine, although mutations causing severe decreases or absence of the enzyme are rare.[140][141] Monitoring blood counts for safety as well as for increase in red cell mean corpuscular volume or induction of mild lymphopenia for establishing a therapeutic response has been suggested.

Other immunosuppressive agents that may be considered include cyclosporine, tacrolimus, mycophenolate, cyclophosphamide, and methotrexate.[1][3][90][97] Cyclosporine is effective, but use is limited due to potential serious adverse effects and drug interactions.[1] Tacrolimus also provides benefit, but is less widely used for MG outside Asia.[98] Evidence for the effectiveness of mycophenolate is equivocal, and randomized controlled trial evidence for methotrexate is lacking; these options may be considered if other options are not tolerated or ineffective.[1][3][90][97][99][100] Cyclophosphamide is associated with significant risk of toxicity, including bone marrow suppression, opportunistic infections, bladder toxicity, sterility, and neoplasms. Therefore, it is used only for patients with severe refractory MG in whom other immunosuppressants are ineffective or not tolerated.[1][90] Mycophenolate, methotrexate, and cyclophosphamide are contraindicated in pregnancy.

Primary options

azathioprine: 50 mg orally once daily initially for 1 week, increase gradually according to response, maximum 2-3 mg/kg/day

Secondary options

cyclosporine non-modified: 2.5 mg/kg orally twice daily initially, increase gradually according to response and serum cyclosporine levels

OR

tacrolimus: consult specialist for guidance on dose

Tertiary options

cyclophosphamide: consult specialist for guidance on dose

OR

mycophenolate mofetil: consult specialist for guidance on dose

OR

methotrexate: consult specialist for guidance on dose

Consider – rituximab or C5 complement inhibitor or efgartigimod alfa

Back
ONGOING
|
severe (class IV or V) or refractory disease
Consider – 

rituximab or C5 complement inhibitor or efgartigimod alfa

Treatment recommended for SOME patients in selected patient group

Rituximab is a treatment option for severe muscle-specific tyrosine kinase (MuSK)‐ or acetylcholine receptor (AChR)‐antibody-positive MG that is refractory to other immunosuppressants.[3][101]​ Evidence suggests that rituximab is effective in patients with MuSK-MG, and it should be considered as an early therapeutic option for these patients if the response to initial immunotherapy is inadequate.[3][101][102]​ For patients with AChR-MG, rituximab is recommended as an option if other immunosuppressant agents are ineffective or not tolerated; however, efficacy in this group is uncertain.[3][114][115][116][117]​ Rituximab is not licensed for the treatment of MG.

Eculizumab and ravulizumab are C5 complement inhibitor monoclonal antibodies. Eculizumab is recommended as a treatment option for severe, refractory, generalized AChR-MG, if other immunotherapies result in an inadequate response or are not tolerated.[3] Studies indicate that eculizumab is an effective and tolerable immunotherapy for refractory severe MG.[123][124][125] Eculizumab may also be suitable for patients with refractory moderate disease, or earlier in the treatment course. Ravulizumab, a longer-acting C5 complement inhibitor, is approved in the US and Europe for treating generalized AChR-MG. In a phase 3 randomized, double-blind trial, ravulizumab was associated with significantly greater improvements in both patient- and clinician-reported outcomes than placebo, with an acceptable safety profile.[126]

All patients taking eculizumab or ravulizumab should be vaccinated against Neisseria meningitidis at least 2 weeks before the first dose to reduce the risk of meningococcal infection. Patients who start treatment less than 2 weeks after receiving a meningococcal vaccine must receive antibacterial drug prophylaxis until 2 weeks after vaccination.

Efgartigimod alfa is a human immunoglobulin G1 (IgG1) antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels. It is available as an intravenous formulation and as a subcutaneous formulation (coformulated with hyaluronidase). Intravenous efgartigimod alfa was well tolerated and more efficacious than placebo in a phase 3 randomized controlled trial of patients with generalized AChR-MG, and is approved in the US and Europe for treating generalized AChR-MG. Adverse effects included respiratory tract infections, headache, and urinary tract infections.[127][128][129]​​ Subcutaneous efgartigimod alfa/hyaluronidase is approved in the US for the treatment of generalized AChR-MG.[130]

Primary options

rituximab: consult specialist for guidance on dose

OR

eculizumab: 900 mg intravenously every 7 days for the first 4 weeks, followed by 1200 mg as a single dose 7 days after the fourth dose, then 1200 mg every 14 days thereafter

More

Secondary options

ravulizumab: body weight 40-59 kg: 2400 mg intravenously as a loading dose, followed by 3000 mg every 8 weeks starting 2 weeks after the loading dose; body weight 60-99 kg: 2700 mg intravenously as a loading dose, followed by 3300 mg every 8 weeks starting 2 weeks after the loading dose; body weight ≥100 kg: 3000 mg intravenously as a loading dose, followed by 3600 mg every 8 weeks starting 2 weeks after the loading dose

More

OR

efgartigimod alfa: body weight <120 kg: 10 mg/kg intravenously once weekly for 4 weeks; body weight ≥120 kg: 1200 mg intravenously once weekly for 4 weeks

More

OR

efgartigimod alfa/hyaluronidase: 1008 mg (efgartigimod alfa)/11,200 units (hyaluronidase) subcutaneously once weekly for 4 weeks

More

Consider – thymectomy

Back
ONGOING
|
severe (class IV or V) or refractory disease
Consider – 

thymectomy

Treatment recommended for SOME patients in selected patient group

Thymectomy should be strongly considered for all patients with generalized acetylcholine receptor (AChR)-MG that is severe and/or in whom a trial of immunosuppressants is ineffective or produces intolerable side effects.[3][90][104][105] There is evidence of less benefit for patients with late-onset MG.[106]

Patients with ocular AChR-MG with an insufficient response to cholinesterase inhibitors may be offered thymectomy if they have contraindications to, are refractory to, or prefer not to take immunosuppressive agents, although there is no large prospective randomized controlled trial of thymectomy in this patient population.[3]

Thymectomy may be considered for patients without detectable AChR antibodies if immunosuppressants are ineffective or to minimize side effects.

There is no evidence to support thymectomy in patients with MuSK, low-density lipoprotein receptor-related protein 4, or agrin antibodies without thymoma.[3]

If a patient has what appears to be thymoma on imaging studies, thymectomy is indicated independent of the type or severity of MG.[1][90]

Thymectomy should be undertaken in an institution where the health professionals are experienced in anesthetic care and perioperative management of patients with MG. Techniques available range from robotic-assisted or video-assisted thoracotomy to thoracotomy using a transcervical or median sternotomy approach.[107][108][109][110] Less invasive approaches are reported to be as effective as more aggressive approaches.[107][108][110] It is generally accepted that the more complete the removal of thymus, the higher the rate of remission in MG symptoms. Surgical risks include injury to phrenic or recurrent laryngeal nerves, pleural effusion, pulmonary embolism, wound infection or delayed healing, and later sternal instability.

Risk factors for myasthenic crisis after thymectomy include preoperative history of myasthenic crisis, preoperative MG severity, preoperative bulbar symptoms, and high-dose pyridostigmine use.[111][112] One systematic review concluded that plasma exchange before surgery may reduce the risk of postoperative myasthenic crisis in patients with severe disease but may have little or no effect in patients with mild disease.[113]

Consider – intravenous immune globulin (IVIG) or plasma exchange

Back
ONGOING
|
severe (class IV or V) or refractory disease
Consider – 

intravenous immune globulin (IVIG) or plasma exchange

Treatment recommended for SOME patients in selected patient group

IVIG or plasma exchange may be an appropriate treatment in the following circumstances: for MG that is refractory to other treatment; as a short-term treatment for patients with MG with or at risk for myasthenic crisis (e.g., respiratory insufficiency or dysphagia); when a rapid response to treatment is needed; before starting corticosteroids if necessary to prevent or minimize exacerbations; and in preparation for surgery to avoid perioperative corticosteroids or other immunosuppressive drugs.[1] Each can be done intermittently (every 4-6 weeks) as an outpatient treatment.

Studies suggest that IVIG and plasma exchange are equally efficacious when compared at 2 weeks post-treatment, so choice of treatment depends on patient factors and availability.[1] The effects of both are temporary.

IVIG is easier to administer than plasma exchange.[118][119][120][121] Onset of response to IVIG is within 4 to 5 days, with maximal response apparent within 1 to 2 weeks. Plasma exchange also elicits a rapid response, with onset usually after 2 to 3 sessions.[81][119][122] IVIG appears to be less effective in MG patients with muscle-specific tyrosine kinase (MuSK) antibodies.[1][50]

IVIG maintenance therapy may be considered for select patients.[1]

Primary options

immune globulin (human): 1000 mg/kg intravenously once daily for 1-2 days

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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