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

Treatment Options for Chronic Immune Thrombocytopenic Purpura (ITP)

The optimal treatment approach for chronic ITP should follow a stepwise algorithm starting with corticosteroids as first-line therapy, followed by thrombopoietin receptor agonists (TPO-RAs), rituximab, or splenectomy as second-line options based on patient-specific factors and response to initial therapy.

First-Line Treatment Options

• Corticosteroids remain the standard initial treatment for chronic ITP with prednisone (1 mg/kg orally for 21 days followed by tapering) recommended as the primary first-line therapy 1
• High-dose dexamethasone (40 mg/day for 4 days) is an effective alternative first-line option with response rates up to 90%, and can be given in cycles every 14-28 days 2, 3
• Long-term responses with high-dose dexamethasone pulse therapy can be achieved in 67-74% of patients 3
• Initial response to corticosteroids occurs in 70-80% of patients, but sustained responses are seen in only 20-40% of cases 1, 4
• Treatment decisions should be based on bleeding severity, bleeding risk, patient activity level, potential side effects, and patient preferences rather than platelet count alone 1
• Intravenous immunoglobulin (IVIg) at 0.4 g/kg/day for 5 days or 1 g/kg/day for 1-2 days can be used when rapid platelet increase is needed or when corticosteroids are contraindicated 1, 2
• IV anti-D (50-75 μg/kg) can be used for Rh(D) positive, non-splenectomized patients as an alternative first-line option 1, 2

Second-Line Treatment Options

Thrombopoietin Receptor Agonists (TPO-RAs)

• Romiplostim (Nplate) is FDA-approved for adult ITP patients when certain medicines or splenectomy have not worked well enough 5
• TPO-RAs are associated with high response rates and can be considered before splenectomy in patients who fail corticosteroid therapy 1
• Romiplostim demonstrated durable platelet responses in 61% of non-splenectomized patients and 38% of splenectomized patients compared to 5% and 0% with placebo, respectively 5
• Weekly subcutaneous administration of romiplostim (median dose 2-3 mcg/kg) effectively maintains platelet counts in the target range of 50-200 × 10^9/L 5
• Potential side effects include risk of blood clots if platelet count becomes too high, and bone marrow fibrosis with long-term use 5

Rituximab

• Rituximab (anti-CD20 monoclonal antibody) achieves responses in 60% of patients with complete responses in 40% of patients 1
• Response typically occurs within 1-8 weeks of treatment initiation 1
• Long-term responses with rituximab are documented in 20-30% of cases 1
• Side effects are generally mild but can include infusion reactions, serum sickness, and rarely progressive multifocal leukoencephalopathy 1

Splenectomy

• Splenectomy has historically been the gold standard second-line therapy with initial response rates of 80% and long-term responses in approximately 60-65% of patients 1, 4
• Response to splenectomy typically occurs within 24 hours 1
• Despite high efficacy, there is increasing reluctance to recommend splenectomy due to surgical risks and long-term complications including risk of overwhelming post-splenectomy infection 1, 4
• In children, splenectomy is rarely recommended due to the 3% risk of post-splenectomy overwhelming sepsis compared to the extremely low risk of death from ITP (0.5%) 1

Third-Line Treatment Options

For patients failing first and second-line therapies, several options can be considered:

• Azathioprine (1-2 mg/kg daily) achieves responses in up to two-thirds of patients but may take 3-6 months for effect 1
• Cyclosporin A (5 mg/kg/day initially, then 2.5-3 mg/kg/day) shows response rates of 50-80% with onset within 3-4 weeks 1
• Cyclophosphamide (1-2 mg/kg orally daily or 0.3-1 g/m² IV every 2-4 weeks) produces responses in 24-85% of patients 1
• Danazol (200 mg 2-4 times daily) achieves responses in up to 67% of patients but requires 3-6 months of treatment 1
• Dapsone (75-100 mg daily) shows responses in up to 50% of patients within 3 weeks 1
• Mycophenolate mofetil (1000 mg twice daily) achieves responses in up to 75% of patients within 4-6 weeks 1

Treatment Algorithm for Chronic ITP

1. Initial Approach:

   • Begin with prednisone 1 mg/kg daily for 21 days followed by tapering 1
   • Alternative: High-dose dexamethasone 40 mg/day for 4 days in cycles 2, 3

2. For patients failing first-line therapy:

   • Consider TPO-RAs (romiplostim) for non-splenectomized patients 5
   • Consider rituximab (375 mg/m² weekly for 4 weeks) particularly in younger patients 1
   • Consider splenectomy in appropriate surgical candidates with severe, symptomatic disease 1

3. For patients failing second-line therapy:

   • Select from third-line options based on comorbidities, side effect profiles, and patient preferences 1
   • Consider combination therapies in refractory cases 1

Special Considerations

• Prolonged corticosteroid use should be avoided due to significant side effects including weight gain, mood alterations, hypertension, diabetes, osteoporosis, and increased infection risk 1, 2
• Treatment for chronic ITP should be tailored to maintain a hemostatic platelet count (typically >30-50 × 10^9/L) rather than normalizing platelet counts 1, 2
• The decision to treat should be based primarily on bleeding symptoms rather than platelet count alone, though counts <20-30 × 10^9/L generally warrant treatment 1, 4
• In children with chronic ITP, the goal is to maintain hemostatic platelet counts while minimizing the use of prolonged corticosteroid therapy 1
• Cytotoxic drugs should be used with extreme caution in children with chronic ITP 1