Myasthenia%20gravis Treatment

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

• 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

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