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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2559-2565. Prepublished online as a Blood First Edition Paper on June 28, 2005; DOI 10.1182/blood-2005-02-0564. This Article Full Text (PDF) All Versions of this Article: 2005-02-0564v1 106/7/2559    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hill, A. Articles by Rother, R. P Search for Related Content PubMed PubMed Citation Articles by Hill, A. Articles by Rother, R. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2005 Accepted May 25, 2005 Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria Anita Hill*, Peter Hillmen, Stephen J Richards, Dupe Elebute, Judith C Marsh, Jason Chan, Christopher F Mojcik, and Russell P Rother Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom Haematology, St Georges Hospital Medical School, London, United Kingdom Alexion Pharmaceuticals, Inc, Cheshire, Connecticut, USA * Corresponding author; email: anitahill{at}doctors.org.uk. Paroxysmal nocturnal hemoglobinuria is a hematological disorder characterized by clonal expansion of red blood cells lacking the ability to inhibit complement-mediated hemolysis. Eculizumab, a humanized monoclonal antibody that binds the C5 complement protein, blocks serum hemolytic activity. This study evaluated the long-term safety and efficacy of eculizumab in 11 PNH patients during an open-label extension trial. Following completion of an initial 12-week study, all patients chose to participate in the 52-week extension study. Eculizumab, 900 mg every 12 to 14 days, was sufficient to completely and consistently block complement activity in all patients. A dramatic reduction in hemolysis was maintained throughout the study with a decrease in LDH levels from 3110.7 IU/L before treatment to 622.4 IU/L (p = 0.002). The proportion of PNH type III RBC increased from 36.7% at baseline to 58.4% (p = 0.005). The paroxysm rate of days with gross evidence of hemoglobinuria/patient/month decreased from 3.0 during screening to 0.2 (p < 0.001) during treatment. The median transfusion rate decreased from 1.8 units/patient/month before eculizumab to 0.3 units/patient/month (p = 0.001) during treatment. Statistically significant improvements in quality of life measures were also maintained during the extension study. Eculizumab continued to be safe and well tolerated, and all patients completed the study. The close relationship between sustained terminal complement inhibition, hemolysis and symptomatology was demonstrated. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New dawn for a nocturnal disease Monica Bessler Blood 2005 106: 2224-2225. [Full Text] [PDF] This article has been cited by other articles: A. M. Risitano, R. Notaro, L. Marando, B. Serio, D. Ranaldi, E. Seneca, P. Ricci, F. Alfinito, A. Camera, G. Gianfaldoni, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab Blood, April 23, 2009; 113(17): 4094 - 4100. [Abstract] [Full Text] [PDF] J. Davis Eculizumab Am. J. Health Syst. Pharm., September 1, 2008; 65(17): 1609 - 1615. [Abstract] [Full Text] [PDF] A. Dmytrijuk, K. Robie-Suh, M. H. Cohen, D. Rieves, K. Weiss, and R. Pazdur FDA Report: Eculizumab (Soliris(R)) for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria Oncologist, September 1, 2008; 13(9): 993 - 1000. [Abstract] [Full Text] [PDF] F. E. Craig and K. A. Foon Flow cytometric immunophenotyping for hematologic neoplasms Blood, April 15, 2008; 111(8): 3941 - 3967. [Abstract] [Full Text] [PDF] R. A. Brodsky, N. S. Young, E. Antonioli, A. M. Risitano, H. Schrezenmeier, J. Schubert, A. Gaya, L. Coyle, C. de Castro, C.-L. Fu, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria Blood, February 15, 2008; 111(4): 1840 - 1847. [Abstract] [Full Text] [PDF] R. L. Haspel and P. Hillmen Which Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Should Be Treated with Eculizumab? Hematology, January 1, 2008; 2008(1): 35 - 35. [Abstract] [Full Text] [PDF] P. Hillmen The Role of Complement Inhibition in PNH Hematology, January 1, 2008; 2008(1): 116 - 123. [Abstract] [Full Text] [PDF] P. Hillmen, P. Muus, U. Duhrsen, A. M. Risitano, J. Schubert, L. Luzzatto, H. Schrezenmeier, J. Szer, R. A. Brodsky, A. Hill, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria Blood, December 1, 2007; 110(12): 4123 - 4128. [Abstract] [Full Text] [PDF] H. Wang, J. Arp, W. Liu, S. J. Faas, J. Jiang, D. R. Gies, S. Ramcharran, B. Garcia, R. Zhong, and R. P. Rother Inhibition of Terminal Complement Components in Presensitized Transplant Recipients Prevents Antibody-Mediated Rejection Leading to Long-Term Graft Survival and Accommodation J. Immunol., October 1, 2007; 179(7): 4451 - 4463. [Abstract] [Full Text] [PDF] S. Mihai, M. T. Chiriac, K. Takahashi, J. M. Thurman, V. M. Holers, D. Zillikens, M. Botto, and C. Sitaru The Alternative Pathway of Complement Activation Is Critical for Blister Induction in Experimental Epidermolysis Bullosa Acquisita J. Immunol., May 15, 2007; 178(10): 6514 - 6521. [Abstract] [Full Text] [PDF] N. J. Hepburn, A. S. Williams, M. A. Nunn, J. C. Chamberlain-Banoub, J. Hamer, B. P. Morgan, and C. L. Harris In Vivo Characterization and Therapeutic Efficacy of a C5-specific Inhibitor from the Soft Tick Ornithodoros moubata J. Biol. Chem., March 16, 2007; 282(11): 8292 - 8299. [Abstract] [Full Text] [PDF] A. Hill, S.J. Richards, R.P. Rother, and P. Hillmen Erythropoietin treatment during complement inhibition with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria Haematologica, March 1, 2007; 92(3): e31 - e33. [Abstract] [Full Text] [PDF] G. R. Buchanan and M. J. Kahn Hemolytic anemias ASH Self-Assessment Program, January 1, 2007; 2007(1): 102 - 142. [Full Text] [PDF] S. K. Kathula, J. Singh, A. K. Malani, M. Pabla, M. Takita, T. Matsumura, M. Kami, Y. B. Pride, and P. Hillmen Eculizumab in paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med., December 28, 2006; 355(26): 2786 - 2786. [Full Text] [PDF] M. C. Pickering, J. Warren, K. L. Rose, F. Carlucci, Y. Wang, M. J. Walport, H. T. Cook, and M. Botto Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice PNAS, June 20, 2006; 103(25): 9649 - 9654. [Abstract] [Full Text] [PDF] S. P. Berger, A. Roos, and M. R. Daha Complement and the kidney: What the nephrologist needs to know in 2006? Nephrol. Dial. Transplant., December 1, 2005; 20(12): 2613 - 2619. [Full Text] [PDF]

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