What are the different therapy methods for psoriasis using cyclosporin (cyclosporine), including dosing and efficacy in dermatology?

Cyclosporin Therapy Methods for Psoriasis: Dosing and Efficacy

Cyclosporin is a highly effective systemic therapy for psoriasis with multiple dosing regimens, producing swift and dramatic improvement in up to 80-90% of patients when dosed at 2.5-5 mg/kg/day for 12-16 weeks. 1

Standard Dosing Regimens

Induction Therapy

• Initial dosing options:
  • Standard approach: 2.5-5 mg/kg/day given orally in divided doses 1
  • Higher dose (5 mg/kg/day): When rapid control is required 1
  • Lower dose (2.5-3 mg/kg/day): When time is less critical 1
  • Fixed-dose option: 100 mg daily (either as single dose or 50 mg twice daily) regardless of weight 1, 2

Efficacy by Dose

• 5 mg/kg/day: Achieves PASI 75 in 50-97% of patients 1
• 3 mg/kg/day: Achieves PASI 75 in 50-70% and PASI 90 in 30-50% of patients 1
• 2.5 mg/kg/day: Achieves PASI 75 in 28-85% of patients 1
• Fixed 100 mg/day: Achieves PASI 50 in 82-84% of patients regardless of weight (for patients 50-80 kg) 2

Administration Timing

• Microemulsion formulation shows better absorption when taken before meals rather than after meals 1
• Can be given as a single daily dose or divided into two doses 1

Maintenance Therapy Approaches

Continuous Maintenance

• Low-dose maintenance: 3 mg/kg/day after induction can maintain remission in 58% of patients for 6 months 3
• Lower doses (1.5 mg/kg/day) are not effective for maintenance, with median time to relapse of 6 weeks (similar to placebo) 1, 3

Intermittent Therapy

• Short-course approach: Use cyclosporin until clearance (typically 4-8 weeks), then discontinue until relapse occurs 1, 4
• Pulse therapy: Low-dose cyclosporin (approximately 2.5 mg/kg/day) given for short periods, then stopped when PASI 75 is achieved 4
• Tapering approach: Gradual tapering (1 mg/kg/day weekly) slightly delays relapse compared to abrupt termination 1

Special Populations

Pediatric Patients

• Cyclosporin is effective for moderate to severe plaque, pustular, and erythrodermic psoriasis in children 1
• Dosing: 2-5 mg/kg/day in divided doses 1
• Children may require higher doses by weight than adults due to faster clearance 1
• Excellent for rapid control of severe, unstable disease in children 1

Combination Therapies

Sequential Therapy

• Low-dose cyclosporin (3 mg/kg/day for 4 weeks) followed by NB-UVB phototherapy shows:
  • Faster resolution of pruritus
  • Reduced number of NB-UVB treatments needed
  • Reduced cumulative UVB exposure 1

Contraindicated Combinations

• Simultaneous cyclosporin + NB-UVB: Contraindicated due to increased risk of photocarcinogenesis 1

Formulation Considerations

• Modified microemulsion formulation (Neoral) is preferred over unmodified cyclosporin (Sandimmune) due to:
  • More consistent absorption
  • Better bioavailability
  • Reduced variability between individuals 1
• Formulations are not interchangeable 1

Monitoring and Safety

Key Adverse Effects

• Nephrotoxicity: Most common serious adverse effect
  • Reversible nephrotoxicity in 19-24% during short-term treatment 1
  • Risk of irreversible kidney damage increases after 2 years of continuous use 1, 5
• Hypertension: Common adverse effect requiring monitoring 1

Monitoring Requirements

• Blood pressure monitoring (early morning readings most sensitive) 1
• Renal function tests (creatinine, BUN) 1
• Consider monthly CBC, potassium, uric acid, lipids, magnesium, bilirubin, and liver enzymes 1

Common Pitfalls to Avoid

1. Extended continuous use: Long-term continuous therapy (>2 years) significantly increases risk of irreversible renal damage 1, 5

2. Inadequate monitoring: Failure to monitor blood pressure and renal function can lead to undetected nephrotoxicity 1

3. Inappropriate combinations: Simultaneous use with phototherapy increases photocarcinogenesis risk 1

4. Formulation switching: Changing between different cyclosporin formulations without dose adjustment can alter efficacy and toxicity 1

5. Ignoring age-related risks: Older patients (>45 years) experience more hypertension and renal function changes with cyclosporin 5

By selecting the appropriate dosing regimen based on disease severity, required speed of response, and patient characteristics, cyclosporin can be an effective tool for managing psoriasis while minimizing potential adverse effects.