Does Azathioprine need to be stopped in a patient with low TPMT activity and no side effects after 4 years of use?

Management of Azathioprine in a Patient with Low TPMT Activity

Azathioprine should not be stopped in a patient with low TPMT activity who has been tolerating the medication well for 4 years without side effects. 1

Understanding TPMT Activity and Azathioprine

Thiopurine methyltransferase (TPMT) is an enzyme responsible for metabolizing azathioprine. Patients with low TPMT activity are generally at higher risk for developing azathioprine toxicity, particularly myelosuppression. However, this risk is most significant during the initial period of treatment.

Risk Assessment Based on TPMT Status:

• Very low/absent TPMT activity (deficient): Azathioprine is contraindicated 1
• Low TPMT activity (heterozygous): Increased risk of toxicity, but can still use azathioprine with:
  • Lower dosing (50% of standard dose) 2
  • More frequent monitoring 1
• Normal TPMT activity: Standard dosing and monitoring

Decision Algorithm for This Patient

1. Duration of stable therapy: The patient has been on azathioprine for 4 years without side effects

   • This demonstrates established tolerance to the medication
   • The highest risk period for myelosuppression is typically early in treatment

2. Current clinical status: No side effects reported

   • Absence of myelosuppression or other toxicity after 4 years suggests individual tolerance despite low TPMT

3. Risk-benefit assessment:

   • Risk: Discontinuing effective therapy may lead to disease flare
   • Benefit: Patient has already demonstrated tolerance to the medication

Monitoring Recommendations

Since the patient has low TPMT activity but is tolerating the medication, continue therapy with:

1. Laboratory monitoring:

   • Complete blood count (CBC) and liver function tests (LFTs) at least once every 3 months 1
   • Consider more frequent monitoring (monthly) due to low TPMT status 1

2. Dose consideration:

   • If not already implemented, consider maintaining at a lower dose (approximately 50% of standard dose) 2
   • Avoid dose increases without careful monitoring

3. Patient education:

   • Instruct the patient to report immediately any signs of:
     • Infection
     • Unexpected bruising or bleeding
     • Jaundice 2, 3

Common Pitfalls to Avoid

1. Unnecessary discontinuation: Stopping a well-tolerated medication after years of stability may cause disease relapse

2. Ignoring established tolerance: The 4-year history without toxicity is strong evidence of individual tolerance despite genetic predisposition

3. Relying solely on TPMT status: While TPMT testing helps identify patients at risk, clinical response and tolerance should guide ongoing management

4. Inadequate monitoring: Even with established tolerance, continued monitoring is essential as toxicity can develop at any time

Conclusion from Evidence

The British Association of Dermatologists guidelines indicate that while patients with low TPMT activity have increased risk of toxicity, alternative therapies should be considered OR a trial of azathioprine at lower doses with careful monitoring can be appropriate 1. In this case, the patient has already demonstrated tolerance over 4 years, which is strong evidence that they can safely continue the medication with appropriate monitoring.