Can azathioprine be used in patients with myasthenia gravis?

Azathioprine in Myasthenia Gravis

Yes, azathioprine is an effective and established treatment for myasthenia gravis, with approximately 83% of patients showing positive response, though it requires 4-10 months before clinical improvement is seen. 1, 2

Evidence for Use in Myasthenia Gravis

Azathioprine has demonstrated clear efficacy in myasthenia gravis across multiple studies:

• 83% of patients improve on azathioprine therapy, with initial clinical response typically occurring after 4-10 months of treatment and peak improvement at approximately 14 months 2
• The drug functions both as monotherapy and as a steroid-sparing agent when combined with corticosteroids 3, 4
• Older patients appear to derive more benefit from azathioprine treatment 4
• Patients with late-onset, severe myasthenia gravis (type II, HLA B8-negative) show particularly good response, with one-third achieving complete remission and two-thirds showing marked improvement 3

Dosing and Titration Strategy

Start with 50-100 mg daily in adults and build up to the target maintenance dose of 2-3 mg/kg/day over the first few weeks to minimize gastrointestinal side effects. 1

• Increase by 25-50 mg increments weekly or biweekly as tolerated 1
• Patients with normal TPMT activity can receive conventional doses (2-3 mg/kg/day), while those with intermediate TPMT activity should receive lower doses (approximately 0.5-1 mg/kg/day) 1
• Critical drug interaction: If the patient is on allopurinol, reduce azathioprine dose to 1/3 to 1/4 of usual dose due to severe myelosuppression risk 1, 5

Absolute Contraindications Before Prescribing

Do not prescribe azathioprine without first checking TPMT status—this is non-negotiable. 6, 5

• Very low or absent TPMT activity is an absolute contraindication due to life-threatening pancytopenia risk 6, 5
• Known hypersensitivity to azathioprine or 6-mercaptopurine 5
• Concurrent allopurinol treatment (or reduce azathioprine dose to 25% if unavoidable) 6, 5
• Pregnancy, except where benefit clearly outweighs risk 6, 5
• Active breastfeeding—6-mercaptopurine appears in breast milk 6, 5
• Known malignancy where immunosuppression may increase disease progression 6, 5

Monitoring and Response Assessment

Do not expect any clinical improvement before 4-6 months of treatment—this latent period is inherent to azathioprine's mechanism of action. 1, 2

• Red blood cell mean corpuscular volume (RBC MCV) is the most useful laboratory marker for monitoring therapeutic efficacy: responders show MCV increases of approximately 15 fl, while non-responders show increases of only 4.5 fl 7
• Continue treatment for at least 6-10 months before assessing efficacy, as patients continue to improve up to 24 months 2
• If discontinuation is attempted after successful treatment, relapse typically occurs within one year 2

Tolerability Considerations

Recent evidence suggests azathioprine has a higher discontinuation rate due to side effects compared to alternative agents like mycophenolate and methotrexate. 8

• The most common side effect is liver dysfunction, occurring in 23% of patients 8
• Women are more likely to experience side effects from azathioprine 8
• Despite higher side-effect burden, there is no significant difference in treatment cessation due to lack of efficacy compared to other immunosuppressants 8

Common Pitfalls to Avoid

• Never start azathioprine without TPMT testing—this is the single most important safety measure 6, 5
• Do not discontinue prematurely—the 4-10 month latent period means apparent "treatment failure" at 3 months may simply reflect insufficient time for drug effect 1, 2
• Do not forget the allopurinol interaction—this can cause life-threatening myelosuppression if azathioprine dose is not reduced to 25% of usual 1, 5
• Do not use standard doses in elderly patients—use the lower end of the dosing range with additional hematological monitoring 5