SOLIRIS (eculizumab): The first treatment specifically approved for PNH

For US Healthcare Professionals

Pathophysiology

Assessment of PNH via flow cytometry is essential for accurate confirmation of the diagnosis and management of PNH.

GPI Anchor Mutation and Deficiency in Cell Surface Proteins in PNH

PNH is an acquired hematopoietic stem cell disorder caused by a somatic mutation in the PIG-A (phosphatidylinositol glycan-complementation class A) gene.1 This mutation prevents all blood cell types from synthesizing the GPI (glycosyl-phophatidylinositol) anchor. The GPI anchor is responsible for binding certain surface
proteins to cell membranes.2,3

PathophysiologyAll PNH cells lack a group of GPI-linked proteins, including an essential group known as complement-regulating surface proteins.3,4 The most important surface protein involved in the complement cascade is CD59 (membrane inhibitor of terminal complement complex formation). Its deficiency, particularly on red blood cells

  • Does not allow for protection against terminal complement1
     
  • Is associated directly with the primary clinical manifestation of PNH — chronic hemolysis1,5

Chronic hemolysis is the underlying cause of the signs and symptoms in PNH, including anemia, disabling fatigue, recurrent pain, dyspnea, smooth muscle dystonias, impaired quality of life and thrombotic events.4-8

Next: The Role of Hemolysis

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTION

SOLIRIS® increases the risk of meningococcal infections.

Vaccinate patients with a meningococcal vaccine at least 2 weeks prior to receiving the first dose of SOLIRIS; revaccinate according to current medication 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.

SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING INCLUDING WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS.

The most frequent adverse events observed in clinical studies were headache, nasopharyngitis, back pain, nausea, fatigue, and cough.

Please see important safety information (including boxed warning) as well as the complete prescribing information.

References:
1. Johnson RJ, Hillmen P. Paroxysmal nocturnal hemoglobinuria: nature's gene therapy? J Clin Pathol Mol Pathol. 2992;55:145-152.
2. Luzzatto L, Gianfaldoni G. Recent advances in biological and clinical aspects of paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2006;84:104-112.
3. Besa EC. Paroxysmal nocturnal hemoglobinuria. eMedicine. August 2006;1-11. Available at: http://www.emedicine.com/med/topic2696.htm Accessed: 5/17/2007.
4. Johnson RJ, Hillmen P. Paroxysmal nocturnal hemoglobinuria: nature's gene therapy? J Clin Pathol Mol Pathol. 2992;55:145-152.
5. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699-3709.
6. Rosse WF, Hillmen P, Schrieber AD. Immune-mediated hemolytic anemia. Hematology. (Am Soc Hematol Educ Program) January 2004:48-62.
7. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ, Shattil SJ, et al. eds. Hematology. 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone. 2005:419-427.
8. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin. JAMA. 2005;293:1653-1662.