Myasthenia%20gravis Treatment
Pharmacotherapy
Treatment goals should focus on complete remission (or minimal manifestations) while causing least possible side effects
Anticholinesterase Agents
- 1st-line therapy for all forms of myasthenia gravis
- Patients usually experience partial improvement; complete improvement occurs in few patients
- No difference in efficacy between different anticholinesterase agents
- Does not stop natural progression of disease state
- Dose and frequency should be tailored to patient’s individual needs
- Muscarinic side effects (eg diarrhea, abdominal cramps, etc) may limit tolerated dose
- Propantheline may be used to block unwanted autonomic side effects
- Loperamide may be used to treat diarrhea
Distigmine
- Longer-acting, but rarely used for myasthenia gravis because of the increased risk of cholinergic crisis
Neostigmine
- An analog of Pyridostigmine with therapeutic effect at approximately 4 hours
- Shorter action and is less effective; with more muscarinic side effects
Pyridostigmine
- Most commonly used anticholinesterase agent
- May be used as long-term treatment in patients with milder disease
- Effect begins within 30 minutes, peaks at about 2 hours and lasts for 3-4 hours
- May be preferable to Neostigmine because of its longer duration of action and is associated with less muscarinic effects
Prednisolone (Prednisone)
- Generally produces improvement of weakness in myasthenia gravis patients
- Based on observational studies, remission or marked improvement occurs in 70-80% of patients
- Start at a low dose to avoid temporary worsening of myasthenia gravis
- Increase dose slowly until marked clinical improvement is seen
- Maintain dose for 1-3 months
- When remission occurs, reduce to minimum effective dose given on alternate days
- Patients need to be observed closely for adverse effects
Immunosuppressants
- Should be considered in patients with progressive myasthenia gravis symptoms
Azathioprine
- Extensively used steroid-sparing immunosuppressant
- Most widely used of the immunomodulatory agents
- May be combined with corticosteroids to add therapeutic effect and/or allow the steroid dose to be reduced
- May take 4-12 months to see beneficial effects, with maximum effect seen at 6-24 months
Ciclosporin
- May be as effective as Azathioprine; may be used alone but is usually combined with steroids
to allow for a reduction of steroid dose - Considered a third-line therapy; should be used only in patients intolerant or unresponsive to other immunosuppressants (eg Azathioprine)
- Beneficial effects are seen in 1-3 months
Cyclophosphamide
- Demonstrated to be effective in treatment-resistant myasthenia gravis cases
- Risk of adverse events limits its use
- Approved by the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) for refractory generalized myasthenia gravis that is acetylcholine receptor antibody-positive
- A humanized monoclonal antibody that binds to C5 and inhibits the formation of C5b-induced membrane attack complex
- Recently approved by the US FDA for the treatment of generalized MG that is AChR antibody-positive
- An antibody fragment that binds to the neonatal Fc receptor (FcRn); thereby preventing FcRN from recycling immunoglobulin G (IgG) back into the blood
- Results in overall reduction of IgG, including the abnormal AChR antibodies
Mycophenolate
- May be considered for long-term therapy if refractory to 1st-line treatment
- Has been shown in small studies to improve functional status or as a steroid-sparing agent
- May be better tolerated than other immunomodulators due to its relative lack of side effects
- Drug is costly and beneficial effects may take months to be seen
Intravenous Immunoglobulin (IVIg)
- May be used to treat myasthenia gravis crisis or to improve a patient’s condition prior to thymectomy or as an adjuvant to minimize side effects with long-term immunosuppressant therapy
- May be used as an alternative to plasmapheresis or immunosuppressive therapy in patients with refractory myasthenia gravis or as preoperative treatment prior to thymectomy
- Rapid improvement occurs in 70% of patients within 4-5 days of treatment
- Can be used in the presence of systemic infection
- Beneficial effect may last for weeks-months
- Drug is expensive
Methotrexate
- According to randomized clinical trials, oral Methotrexate may be beneficial in generalized myasthenia gravis who cannot tolerate or respond to steroid-sparing agents
- In studies, it appears to be particularly effective in patients with muscle specific tyrosine kinase-positive myasthenia gravis that often respond relatively poorly to first-line immunosuppressive therapies
Tacrolimus
- Widely used in Japan for the management of myasthenia gravis in patients who underwent thymectomy and with poor response to steroid therapy
Non-Pharmacological Therapy
Plasmapheresis
- May be used to treat myasthenia gravis crisis or to improve a patient’s condition prior to thymectomy
- Pathogenic antibodies are separated from the blood cells mechanically
- Useful in decreasing symptoms when starting immunosuppressive therapy
- 5 exchanges (3-4 L/exchange) are performed over a 2-week period
- Rapid short-term clinical improvement in most patients due to reduction in anti-acetylcholine receptor antibodies
- Not recommended in patients with cardiac failure, sepsis, hypotension, and pregnancy
- Not recommended as a treatment to obtain a continuous and lasting immunosuppression in myasthenia gravis
- Not considered to be a suitable procedure in pediatric patients