What are the treatment options for Immune Thrombocytopenic Purpura (ITP)?

Treatment Options for Immune Thrombocytopenic Purpura (ITP)

Thrombopoietin receptor agonists (TPO-RAs) such as eltrombopag or romiplostim are the preferred second-line options for ITP patients who are corticosteroid-dependent or unresponsive to corticosteroids, offering better long-term efficacy and safety profiles than other alternatives. 1

First-Line Treatment

Corticosteroids

• Initial therapy: Prednisone 1-2 mg/kg/day for adults or 4 mg/kg/day for 7 days followed by gradual reduction for children 1
• Treatment goal: Achieve platelet count ≥30-50 × 10⁹/L
• Duration: Should be limited to 4-6 weeks maximum to avoid significant adverse effects 2
• Alternative: High-dose methylprednisolone (30 mg/kg/day for 3 days followed by 20 mg/kg/day for 4 days) for rapid response 2, 1
• Important caveat: Prolonged corticosteroid use (>6-8 weeks) should be avoided due to significant adverse effects including weight gain, osteoporosis, cataracts, hypertension, and infections 2, 1

Other First-Line Options

• Intravenous immunoglobulin (IVIg): For patients with severe bleeding or requiring rapid platelet increase 2, 1
• Anti-D immunoglobulin: Alternative to IVIg in Rh-positive, non-splenectomized patients 2, 1

Second-Line Treatment

Thrombopoietin Receptor Agonists (TPO-RAs)

• Preferred second-line option for most patients with ITP duration >1 year 2, 1
• Romiplostim: Weekly subcutaneous injection, starting at 1 mcg/kg/week with dose adjustments to maintain platelet count 50-200 × 10⁹/L 3
  • Demonstrated 88% overall response rate in non-splenectomized patients and 79% in splenectomized patients 3
  • Requires regular monitoring of platelet counts
  • Potential risk of blood clots if platelet count becomes too high 3
• Eltrombopag: Daily oral medication, alternative to romiplostim 2, 1
• Switching between TPO-RAs: If a patient doesn't respond to one TPO-RA, switching to the other often results in response 2
• Monitoring: Use minimum dose necessary to maintain target platelet count; watch for potential remissions 2

Splenectomy

• Effective option with 60-70% long-term response rate 2
• Consider for eligible patients who prefer surgical treatment 2
• Important considerations:
  • Long-term risks include delayed relapse, infection, thromboembolism, and possibly cancer 2
  • 80% of responders maintain platelet response over 4 years 2
  • Should be discussed thoroughly with patients given its permanent nature 2

Rituximab

• Not recommended as standard second-line therapy due to:
  • Variable and unpredictable time to response (1-8 weeks) 2
  • Limited long-term benefits in most patients 2
  • Reduced efficacy in male patients and those with ITP >1 year 2
  • Response rates of 31-79% reported, but long-term responses only in 20-30% of cases 2
  • Potential risks including hepatitis B reactivation and multifocal leukoencephalopathy 2

Third-Line and Beyond Options

Combination Therapies

• Cyclosporin A, azathioprine, prednisone, IVIg, anti-D, vinca alkaloids, and danazol 2
• Approximately 70% of patients achieve platelet response 2
• Response time varies from days to months 2

Treatment Algorithm

1. Initial assessment:

   • If platelet count <20-30 × 10⁹/L or active bleeding: Start first-line therapy
   • If platelet count >30 × 10⁹/L without significant bleeding: Observation may be appropriate

2. First-line therapy:

   • Corticosteroids (prednisone 1-2 mg/kg/day)
   • Add IVIg or anti-D for severe bleeding or need for rapid platelet increase

3. Transition to second-line therapy if:

   • Patient cannot tolerate first-line treatment
   • No response within 2-4 weeks
   • Response lost within 6 months
   • Unable to taper corticosteroids to low dose (≤5 mg/day prednisone) 2

4. Second-line therapy:

   • TPO-RAs (romiplostim or eltrombopag) for most patients with ITP >1 year
   • Splenectomy for eligible patients who prefer surgical treatment
   • If no response to one TPO-RA, try the alternate TPO-RA

5. Third-line options for refractory cases:

   • Combination therapies
   • Consider clinical trials

Special Considerations

• Platelet transfusions: Only for active bleeding with thrombocytopenia or very severe thrombocytopenia (<10,000/μL) with high bleeding risk 1
• TPO-RA discontinuation: If no response after 4 weeks at maximum dose 1
• Monitoring: Weekly platelet count monitoring during treatment initiation, with monthly monitoring after establishing stable platelet counts 1
• Pediatric patients: Cytotoxic drugs should be used with extreme caution; all children with persistent or chronic ITP should be managed by a hematologist experienced in pediatric ITP 2

By following this treatment approach and considering the individual patient's response, bleeding risk, and tolerance to therapy, most patients with ITP can achieve safe platelet counts and improved quality of life.