What is the treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)

Eculizumab is the primary treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH) to reduce hemolysis, prevent thrombosis, and improve survival. 1, 2

Diagnosis and Initial Evaluation

• PNH diagnosis requires flow cytometry to evaluate loss of GPI-anchored proteins on blood cells 3
• Testing should include complement levels (C3, C4, CH50) and evaluation for GPI-negative cells by flow cytometry 3
• A complete blood count with peripheral smear, reticulocyte count, LDH, and haptoglobin should be performed to assess the degree of hemolysis 3
• Direct antibody test (Coombs test) should be conducted to rule out other causes of hemolysis 3

First-Line Treatment

• Eculizumab (Soliris), a C5 inhibitor, is FDA-approved for PNH treatment to reduce hemolysis 1
• For patients 18 years and older, the dosing regimen is:
  • 600 mg weekly for the first 4 weeks
  • 900 mg for the fifth dose 1 week later
  • 900 mg every 2 weeks thereafter 1
• Prior to initiating eculizumab, patients must be vaccinated against meningococcal infection (serogroups A, C, W, Y, and B) at least 2 weeks before the first dose 1
• If urgent therapy is needed before vaccination can be completed, antibacterial prophylaxis should be provided 1

Alternative Treatment Options

• Ravulizumab (Ultomiris), a longer-acting C5 inhibitor, is also FDA-approved for PNH in adults and pediatric patients one month of age and older 4, 5
• Ravulizumab allows for extended dosing intervals (every 8 weeks) compared to eculizumab (every 2 weeks), improving patient convenience 5
• Newer complement inhibitors targeting different parts of the complement cascade (pegcetacoplan, iptacopan, danicopan) may be considered for patients with suboptimal response to anti-C5 therapy 5

Monitoring and Follow-up

• Regular monitoring of hemoglobin, LDH, reticulocyte count, and clinical symptoms is necessary 3
• Patients should be monitored for breakthrough hemolysis, particularly during infections, trauma, or surgery 5
• Thrombotic events should be closely monitored as they are a major cause of morbidity and mortality in PNH 2

Special Considerations

• For patients with both PNH and thrombosis, indefinite anticoagulant treatment should be given 3
• Patients with PNH who undergo allogeneic hematopoietic stem cell transplantation (HSCT) may benefit from prophylactic eculizumab in the early post-transplantation period to prevent hemolysis and thrombosis 6
• HSCT is curative but should be reserved for the most severely affected patients due to associated risks 3
• Patients with PNH and underlying myeloproliferative neoplasms should receive appropriate anti-proliferative therapy in addition to complement inhibition 3

Treatment Efficacy and Outcomes

• Eculizumab treatment has been shown to:
  • Reduce intravascular hemolysis by 87% 7
  • Decrease thrombotic events from 5.6 to 0.8 events per 100 patient-years 2
  • Improve survival to levels similar to the general population 2
  • Allow for transfusion independence in 66% of patients treated for more than 12 months 2
  • Improve symptoms of fatigue and dyspnea within 1-2 weeks of treatment 7
  • Improve chronic kidney disease in 41% of patients 7

Complications and Risks

• The most serious risk of complement inhibitor therapy is increased susceptibility to infections with encapsulated bacteria, particularly Neisseria meningitidis 1
• Patients must be enrolled in the ULTOMIRIS and SOLIRIS REMS program due to the risk of serious meningococcal infections 1
• Breakthrough hemolysis may occur during complement-amplifying conditions such as infections, trauma, or surgery 5

PNH is a rare but serious hematologic disorder that, if left untreated, leads to significant morbidity and mortality. With the advent of complement inhibitors, particularly eculizumab, the natural history of the disease has been dramatically altered, with improved survival and quality of life for affected patients.