Systemic Threats of Hemolysis Include Progression to End Organ Damage or Failure1,2
64% of PNH patients have CKD and nearly 50% have evidence of pulmonary hypertension (PHT)3,4
- Renal insufficiency prevalence in PNH is 6.6x higher than reported for the general population 3,5
- Renal failure was identified as the cause of death in approximately 8% to 18% of PNH patients6
- 59% of PNH patients with minimal transfusion history (0-1 transfusions) had CKD3
PNH patients are also at risk for end organ damage or failure, including brain, liver, GI system, and lung.1,2,7
Pulmonary hypertension (PHT) can be linked to hemolysis and resulting nitric oxide (NO) depletion8
- Hemolysis levels and NO consumption were shown to be much greater in patients with PNH than in patients with other hemolytic diseases (6- to 10-fold, respectively)4
- Evidence of PHT in PNH patients has been observed using 2 key measures for PHT4
- Doppler echocardiography7
- NT-proBNP level (≥160 pg/mL)4
- PNH patients with PHT present with cardiac dysfunction4
Symptoms of PHT commonly found in patients with PNH8,9
- 66% of patients reported shortness of breath9
- 72% of those patients qualified shortness of breath as moderate to severe9
- 88% of those patients reported distress due to dyspnea9
Other PNH symptoms that may be associated with NO deficiency include abdominal pain, dysphagia, and erectile dysfunction.10
IMPORTANT SAFETY INFORMATION
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
Soliris increases the risk of meningococcal infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early
- Vaccinate patients with a meningococcal vaccine at least 2 weeks prior to receiving the first dose of Soliris; revaccinate according to current medical guidelines for vaccine use
- Monitor patients for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary
The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.
The most frequent adverse events observed in clinical studies were headache, nasopharyngitis, back pain, nausea, and fatigue.
SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING INCLUDING WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS.
References: 1. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293:1653-1662.
2. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25:1256-1264.
3. Hillmen P, Elebute MO, Kelly R, et al. High incidence of progression to chronic renal insufficiency in patients with paroxysmal nocturnal hemoglobinuria (PNH) [ASH abstract]. Blood. 2007;110: Abstract 3678.
4. Hill A, Rother RP, Wang X, et al. Eculizumab reduces pulmonary hypertension through inhibition of hemolysis-associated nitric oxide consumption in patients with paroxysmal nocturnal hemoglobinuria [ASH abstract]. Blood.2008;112: Abstract 486.
5. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
6. Nishimura J-I, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine. 2004;83:193-207.
7. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258.
8. Hill A, Wang X, Sapsford RJ, et al. Nitric oxide consumption and pulmonary hypertension in patients with paroxysmal nocturnal hemoglobinuria [ASH abstract]. Blood. 2005;106: Abstract 1046.
9. Meyers G, Weitz I, Lamy T, et al. Disease-related symptoms reported across a broad population of patients with paroxysmal nocturnal hemoglobinuria [ASH abstract]. Blood. 2007;110: Abstract 3683.
10. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007;137:181-192.
11. Rosse WF. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:331-342.