What is Paroxysmal Nocturnal Hemoglobinuria (PNH)?

From the Guidelines

Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) should be routinely tested for the condition, especially those with Budd-Chiari syndrome (BCS), as PNH has been reported in 9-19% of tested BCS patients 1. PNH is a rare acquired haematological disorder of haematopoietic stem cells, and its exact mechanism for the development of splanchnic vein thrombosis (SVT) is yet unknown 1.

• Key factors associated with PNH include:
  • A prevalence of 0-2% in portal vein thrombosis (PVT) patients 1
  • A greater risk for thrombosis in patients with a PNH cell population above 60% of the granulocytes 1
  • Association with autoimmune-mediated diseases, inflammatory bowel disease, vasculitis, sarcoidosis, and connective tissue disease, although these disorders are hardly observed in some studies 1
• Testing for PNH should be performed in all BCS patients and considered in PVT patients 1, as early diagnosis and treatment are crucial to prevent life-threatening complications like thrombosis and improve quality of life.
• Other risk factors for SVT, such as hormonal factors, including oral contraceptive use and pregnancy, should also be considered, as they may increase the risk of BCS and PVT 1.

From the FDA Drug Label

1.1 Paroxysmal Nocturnal Hemoglobinuria ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).

1. 1 Paroxysmal Nocturnal Hemoglobinuria (PNH) SOLIRIS is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

PNH Treatment:

• Ravulizumab (ULTOMIRIS) is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH) 2.
• Eculizumab (SOLIRIS) is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis 3. Key Points:
• Both ravulizumab and eculizumab are used to treat PNH.
• The treatment options are available for patients with PNH, with specific dosage regimens for each medication.

From the Research

Definition and Treatment of PNH

• Paroxysmal nocturnal hemoglobinuria (PNH) is a rare stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis 4.
• The treatment of PNH has evolved with the introduction of complement inhibitors, such as eculizumab and ravulizumab, which have been shown to decrease intravascular hemolysis and thrombosis and improve survival 5, 6.

Ravulizumab as a Treatment Option

• Ravulizumab is a long-acting, second-generation complement component 5 (C5) inhibitor that is administered intravenously every 8 weeks 5.
• Ravulizumab has been shown to be non-inferior to eculizumab in terms of efficacy and safety for the treatment of patients with PNH 4, 5.
• Ravulizumab is likely to replace eculizumab as the first-line treatment for PNH due to its more convenient dosing schedule and reduced risk of breakthrough hemolysis 5.

Safety and Efficacy of Ravulizumab

• Ravulizumab has been found to be safe and well-tolerated in phase 3 trials, with a lower risk of breakthrough hemolysis compared to eculizumab 7.
• Long-term safety data for ravulizumab treatment are needed, but available data suggest that it provides durable control of terminal complement activity and intravascular hemolysis, resulting in a low incidence of major adverse vascular events 8.
• Ravulizumab has been shown to reduce the risk of mortality by five-fold compared to untreated patients with PNH 8.

Breakthrough Hemolysis Events

• Breakthrough hemolysis events are less common with ravulizumab compared to eculizumab, and are often associated with complement-amplifying conditions rather than suboptimal C5 inhibition 7.
• The immediate, complete, and sustained C5 inhibition achieved through weight-based dosing of ravulizumab reduces the risk of breakthrough hemolysis by eliminating events associated with suboptimal C5 inhibition 7.