Drugs

, Volume 68, Issue 10, pp 1341–1346

Eculizumab in Paroxysmal Nocturnal Haemoglobinuria

Leading Article

Abstract

Eculizumab is a monoclonal antibody that binds with high affinity to the complement protein C5, preventing terminal complement-mediated intravascular haemolysis in patients with paroxysmal nocturnal haemoglobinuria (PNH). In three well designed clinical trials in patients with PNH, eculizumab blocked serum haemolytic activity and decreased transfusion rates. Pooled data from the three clinical trials demonstrated that eculizumab treatment decreased the overall thromboembolism rate in patients with PNH. Eculizumab carries a black box warning for the potential increased risk of meningococcal infections and requires patients to receive the meningococcal vaccine at least 2 weeks before starting treatment. Eculizumab is the first drug to be approved by the US FDA for the treatment of PNH and is a novel treatment that offers a new option for patients with PNH.

References

  1. 1.
    Strubing P. Paroxysmale haemoglobinurie. Deutsche Med Wochenschrift 1882; 8: 1–16CrossRefGoogle Scholar
  2. 2.
    Nishimura J, Murakami Y, Kinoshita T. Paroxysmal noctrnal hemoglobinuria: an acquired genetic disease. Am J Hematol 1999; 62: 175–82PubMedCrossRefGoogle Scholar
  3. 3.
    Brodsky RA. New insights into paroxysmal nocturnal hemoglobinuria. Hematology Am Soc Hematol Educ Program 2006; 24-8: 516Google Scholar
  4. 4.
    Meletis J, Terpos E. Recent insights into pathophysiology of paroxysmal nocturnal hemoglobinuria. Med Sci Monit 2003; 9: 161–72Google Scholar
  5. 5.
    Parker CJ. The pathophysiology of paroxysmal nocturnal hemoglobinuria. Exp Hematol 2007; 35: 523–33PubMedCrossRefGoogle Scholar
  6. 6.
    Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol 2007; 137: 181–92PubMedCrossRefGoogle Scholar
  7. 7.
    Parham Peter, editor. The immune system. New York: Garland Publishing/Elsevier science Ltd., 2000: 185Google Scholar
  8. 8.
    Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995; 333: 1253–8PubMedCrossRefGoogle Scholar
  9. 9.
    Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106: 3699–709PubMedCrossRefGoogle Scholar
  10. 10.
    FDA News. FDA approves first-of-its-kind drug to treat rare blood disorder [online]. Available from URL: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01589.html [Accessed 2007 Nov 1]
  11. 11.
    Soliris (eculizumab) prescribing information. Cheshire (CT): Alexion Pharmaceuticals, Inc.Google Scholar
  12. 12.
    Matis LA, Rollins SA. Complement-specific antibodies: designing novel anti-inflammatories. Nat Med 1995; 1: 839–42PubMedCrossRefGoogle Scholar
  13. 13.
    Hillmen P, Hall C, Marsh J, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2004; 350: 552–9PubMedCrossRefGoogle Scholar
  14. 14.
    Hill A, Hillmen P, Richards SJ, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood 2005; 106: 2559–65PubMedCrossRefGoogle Scholar
  15. 15.
    Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006; 355: 1233–43PubMedCrossRefGoogle Scholar
  16. 16.
    Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 2008; 111: 1840–7PubMedCrossRefGoogle Scholar
  17. 17.
    Hillmen R, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007; 110: 4123–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of Pharmacy Practice and ScienceUniversity of MarylandRockvilleUSA
  2. 2.Department of Clinical Pharmacy PracticeSt. John’s UniversityQueensUSA

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