Drugs for Myasthenia Gravis

Drugs for myasthenia gravis improve neuromuscular transmission or suppress the autoimmune attack on the acetylcholine receptor and related proteins. Treatment combines symptomatic drugs, immunosuppression, rapid immunotherapy for crisis, and thymectomy in selected patients.

Classification. Cholinesterase inhibitors (pyridostigmine), corticosteroids, steroid-sparing immunosuppressants (azathioprine, mycophenolate, methotrexate, tacrolimus, ciclosporin), biologics (rituximab, complement inhibitors, neonatal Fc receptor blockers), and rapid therapies (intravenous immunoglobulin, plasma exchange).

• Pyridostigmine 30 to 60 mg three to four times daily, increased to 60 to 120 mg every 4 to 6 hours; maximum 360 mg daily in most patients.
• Prednisolone starting 10 to 20 mg daily, increased gradually to 1 mg/kg daily (maximum 60 to 80 mg), then tapered to the lowest effective alternate-day dose.
• Azathioprine 2 to 3 mg/kg daily; mycophenolate 1 g twice daily.
• Rituximab, eculizumab, ravulizumab, efgartigimod: specialist biologics.
• Intravenous immunoglobulin 2 g/kg over 2 to 5 days; plasma exchange of 1 to 1.5 plasma volumes, 5 exchanges over 10 to 14 days.

Differences. Pyridostigmine relieves symptoms only. Steroids act in weeks and azathioprine in 6 to 12 months. Intravenous immunoglobulin and plasma exchange act within days.

• Ocular and mild generalised disease: pyridostigmine; add prednisolone if symptoms persist.
• Generalised disease: prednisolone with azathioprine or mycophenolate; thymectomy for acetylcholine receptor antibody-positive generalised disease and thymoma.
• Myasthenic crisis: admit to intensive care; intubate when forced vital capacity falls under 15 to 20 mL/kg; give intravenous immunoglobulin or plasma exchange; hold pyridostigmine while ventilated; treat infection.
• Starting high-dose steroids: can cause transient worsening in 1 to 2 weeks; start low and increase, or give while admitted.
• Before immunosuppression: exclude tuberculosis, hepatitis B and HIV. In areas where strongyloides is endemic, give ivermectin 200 microgram/kg as a single dose before steroids.
• Drugs to avoid or use with caution: aminoglycosides, fluoroquinolones, macrolides, intravenous magnesium, beta blockers, chloroquine, hydroxychloroquine, quinine, botulinum toxin, and neuromuscular blockers (sensitivity).

Selection. Add bone protection (calcium, vitamin D) and gastroprotection with steroids; check glucose and blood pressure.

Contraindications. Pyridostigmine in mechanical bowel or urinary obstruction.

Adverse effects. Pyridostigmine: diarrhoea, cramps, salivation, sweating, bradycardia, muscle twitching; excess causes weakness (cholinergic crisis). Steroids: hyperglycaemia, osteoporosis, infection, psychosis. Azathioprine: myelosuppression, hepatotoxicity. Mycophenolate: myelosuppression, diarrhoea, teratogenicity. Immunoglobulin: headache, thrombosis, kidney injury.

Interactions. Allopurinol with azathioprine needs a 66 to 75 percent dose reduction. Antimuscarinic drugs mask cholinergic effects.

Special groups.

• Pregnancy: pyridostigmine, prednisolone and azathioprine acceptable; mycophenolate and methotrexate contraindicated. Monitor the newborn for transient neonatal myasthenia.
• Breastfeeding: azathioprine, prednisolone and pyridostigmine acceptable.
• Kidney impairment: reduce pyridostigmine doses.
• Older adults: slower steroid titration.

Monitoring. Symptom scores, forced vital capacity, full blood count and liver enzymes (azathioprine and mycophenolate), glucose, blood pressure and bone health.

Referral and escalation. All new diagnoses need specialist review. Bulbar symptoms, breathlessness, rapidly worsening weakness or aspiration are emergencies.