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

Treatment Options for Chronic Immune Thrombocytopenic Purpura (ITP)

Thrombopoietin receptor agonists (TPO-RAs) are the preferred second-line therapy for long-term management of chronic ITP due to their high response rates, sustained efficacy, and favorable safety profile compared to other options. 1

First-Line Treatment Options

• Corticosteroids remain the standard initial treatment for chronic ITP 2, 1
• Prednisone (1 mg/kg orally for 21 days followed by tapering) is recommended as primary first-line therapy 1
• Initial response to corticosteroids occurs in 70-80% of patients, but sustained responses are seen in only 20-40% of cases 1, 3
• High-dose dexamethasone (40 mg/day for 4 days, given every 2-4 weeks for 1-4 cycles) offers up to 90% initial response rates and 50-80% sustained response rates 4, 5
• Intravenous immunoglobulin (IVIg) at 1 g/kg/day for 1-2 days can be used when rapid platelet increase is needed or when corticosteroids are contraindicated 2, 1
• IV anti-D (50-75 μg/kg) can be used for Rh(D) positive, non-splenectomized patients as an alternative first-line option 1

Second-Line Treatment Options

• TPO-RAs (romiplostim, eltrombopag) are the preferred second-line therapy with overall platelet response rates of 88% in non-splenectomized and 79% in splenectomized patients 1, 6
• Romiplostim is administered subcutaneously once weekly with dose adjustments to maintain platelet counts between 50-200 × 10^9/L 6
• Rituximab (anti-CD20 monoclonal antibody) achieves responses in 60% of patients with complete responses in 40% of patients, with response typically occurring within 1-8 weeks 2, 1
• Long-term responses with rituximab are documented in 20-30% of cases 1
• 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 2, 1, 7

Third-Line Treatment Options

• 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

1. Initial Assessment: 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

2. First-Line Treatment:

   • Begin with prednisone (1 mg/kg/day for 21 days then taper) 1
   • Alternative: High-dose dexamethasone (40 mg/day for 4 days) for faster response 4, 5

3. Second-Line Treatment (if no response to first-line or relapse):

   • TPO-RAs (romiplostim or eltrombopag) are preferred due to high efficacy and favorable safety profile 1, 6
   • Rituximab may be considered before splenectomy 2, 1
   • Splenectomy remains effective but is increasingly deferred due to surgical risks and potential for post-splenectomy complications 2, 7

4. Third-Line Treatment (if no response to second-line):

   • Consider immunosuppressive agents (azathioprine, cyclosporin A, cyclophosphamide) 1
   • Other options include danazol, dapsone, or mycophenolate mofetil 1

Important Considerations and Pitfalls

• Treatment should aim to maintain a hemostatic platelet count (>30-50 × 10^9/L) rather than normalizing platelet counts 1
• 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, 7
• Prolonged corticosteroid use (>6-8 weeks) should be avoided due to significant side effects including weight gain, mood alterations, hypertension, diabetes, osteoporosis, and increased infection risk 1, 4
• Patients requiring on-demand administration of corticosteroids after completing first-line treatment should be considered non-responders and promptly switched to second-line therapy 1
• TPO-RAs were previously thought to require lifelong administration, but evidence now shows up to 30% of patients may achieve remission after discontinuation 1
• When switching between TPO-RAs due to lack of efficacy, most patients will respond to the alternate agent 1
• Abrupt interruptions of TPO-RAs or excessive dose adjustments may cause platelet fluctuations and should be avoided 1
• Romiplostim carries risks of blood clots if platelet counts become too high during treatment 6