What is the role of azathioprine (immunosuppressive medication) in the treatment of psoriasis?

Azathioprine in Psoriasis Treatment

Azathioprine has limited evidence for effectiveness in psoriasis and is now rarely used in clinical practice, though it may be considered as an alternative therapy when other treatments have failed or are contraindicated. 1

Role of Azathioprine in Psoriasis Management

Azathioprine is an immunosuppressive medication that works through multiple mechanisms:

• Inhibits purine synthesis
• Incorporates 6-thioguanine nucleotides (6-TGNs) into DNA, contributing to cytotoxicity
• Suppresses T-cell effects and alters antibody production
• Reduces immunoinflammatory responses 2

Current Position in Treatment Algorithm

• Unlicensed indication: Azathioprine is not FDA-approved for psoriasis treatment 1
• Limited evidence base: Only a few studies support its use as monotherapy in moderate-to-severe psoriasis 1
• Alternative role: May be considered when other therapies have failed or are contraindicated 3
• Combination therapy: Can potentially be combined with biologics such as infliximab as an alternative to methotrexate for long-term maintenance 1

Efficacy in Psoriasis

Recent studies have shown varying degrees of efficacy:

• Weekly pulse therapy: 300mg once weekly has shown promise:

  • PASI 75 achieved in 42% of patients
  • PASI 90 in 36% of patients
  • PASI 100 in 22% of patients 4

• Comparative efficacy: When compared to methotrexate in a randomized controlled trial:

  • Azathioprine weekly pulse (300mg): 47.5% achieved PASI 75 (intention-to-treat analysis)
  • Methotrexate weekly (15mg): 85% achieved PASI 75 (intention-to-treat analysis) 3

• Prolonged remission: Some studies suggest azathioprine pulse therapy may produce durable remission in psoriasis patients 5

Dosing Strategies

Two main approaches have been studied:

1. Daily dosing: 1-3 mg/kg/day based on TPMT activity level 6

2. Weekly pulse therapy: 300 mg once weekly, which has shown efficacy in several immune-mediated dermatological conditions including psoriasis 7

Safety Considerations and Monitoring

TPMT Testing

• Critical safety measure: TPMT testing is essential before starting azathioprine to prevent potentially life-threatening myelosuppression 6, 2
• Genetic polymorphisms: Approximately 0.3% of patients have little or no TPMT activity (homozygous deficient), while about 10% have intermediate activity (heterozygous deficient) 2
• Dose adjustment: Patients with TPMT deficiency require alternative therapy or dose modification 2

Adverse Effects

• Hematological: Myelosuppression, particularly in patients with TPMT deficiency
• Hepatic: Liver toxicity reported at higher frequency compared to other agents like mycophenolate mofetil 1
• Gastrointestinal: Nausea, vomiting
• Other concerns: In older studies, minimal cholestasis was seen in some cases and portal fibrosis of a reversible degree in others 8

Monitoring Requirements

• Regular complete blood count
• Liver function tests
• Consider periodic liver biopsies for long-term therapy to detect structural liver damage at an early, reversible stage 8
• Avoid concomitant use with allopurinol (increases azathioprine toxicity) 6

Practical Approach to Using Azathioprine in Psoriasis

1. Consider azathioprine when:

   • Patient has failed or has contraindications to first-line systemic therapies (methotrexate, cyclosporine, biologics)
   • Other treatment options are unavailable or unsuitable

2. Before initiating:

   • Perform TPMT testing (mandatory)
   • Complete baseline laboratory evaluation (CBC, liver function, renal function)

3. Dosing options:

   • Daily dosing: 1-3 mg/kg/day based on TPMT activity
   • Weekly pulse: 300 mg once weekly (alternative regimen with potentially fewer side effects)

4. Monitoring:

   • CBC and liver function tests every 1-2 weeks initially, then monthly
   • Assess clinical response after 12+ weeks (full benefit may take time)

5. Duration:

   • Consider maintenance therapy in responders
   • Monitor for relapse after discontinuation

Conclusion

While azathioprine has shown some efficacy in psoriasis treatment, its role is limited by the availability of more effective and better-studied alternatives. It remains a valuable option in specific clinical scenarios, particularly for patients who cannot use other systemic therapies.