Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria - PubMed (original) (raw)
Clinical Trial
. 2004 Feb 5;350(6):552-9.
doi: 10.1056/NEJMoa031688.
Affiliations
- PMID: 14762182
- DOI: 10.1056/NEJMoa031688
Free article
Clinical Trial
Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria
Peter Hillmen et al. N Engl J Med. 2004.
Free article
Abstract
Background: Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell and the subsequent production of blood cells with a deficiency of surface proteins that protect the cells against attack by the complement system. We tested the clinical efficacy of eculizumab, a humanized antibody that inhibits the activation of terminal complement components, in patients with PNH.
Methods: Eleven transfusion-dependent patients with PNH received infusions of eculizumab (600 mg) every week for four weeks, followed one week later by a 900-mg dose and then by 900 mg every other week through week 12. Clinical and biochemical indicators of hemolysis were measured throughout the trial.
Results: Mean lactate dehydrogenase levels decreased from 3111 IU per liter before treatment to 594 IU per liter during treatment (P=0.002). The mean percentage of PNH type III erythrocytes increased from 36.7 percent of the total erythrocyte population to 59.2 percent (P=0.005). The mean and median transfusion rates decreased from 2.1 and 1.8 units per patient per month to 0.6 and 0.0 units per patient per month, respectively (P=0.003 for the comparison of the median rates). Episodes of hemoglobinuria were reduced by 96 percent (P<0.001), and measurements of the quality of life improved significantly.
Conclusions: Eculizumab is safe and well tolerated in patients with PNH. This antibody against terminal complement protein C5 reduces intravascular hemolysis, hemoglobinuria, and the need for transfusion, with an associated improvement in the quality of life in patients with PNH.
Copyright 2004 Massachusetts Medical Society
Similar articles
- The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.
Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, Röth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L. Hillmen P, et al. N Engl J Med. 2006 Sep 21;355(12):1233-43. doi: 10.1056/NEJMoa061648. N Engl J Med. 2006. PMID: 16990386 Clinical Trial. - Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria.
Hill A, Hillmen P, Richards SJ, Elebute D, Marsh JC, Chan J, Mojcik CF, Rother RP. Hill A, et al. Blood. 2005 Oct 1;106(7):2559-65. doi: 10.1182/blood-2005-02-0564. Epub 2005 Jun 28. Blood. 2005. PMID: 15985537 Clinical Trial. - Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria.
Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Brodsky RA, et al. Blood. 2008 Feb 15;111(4):1840-7. doi: 10.1182/blood-2007-06-094136. Epub 2007 Nov 30. Blood. 2008. PMID: 18055865 Clinical Trial. - Treatment of paroxysmal nocturnal hemoglobinuria in the era of eculizumab.
Röth A, Dührsen U. Röth A, et al. Eur J Haematol. 2011 Dec;87(6):473-9. doi: 10.1111/j.1600-0609.2011.01701.x. Eur J Haematol. 2011. PMID: 21883481 Review. - New insights into paroxysmal nocturnal hemoglobinuria.
Savage WJ, Brodsky RA. Savage WJ, et al. Hematology. 2007 Oct;12(5):371-6. doi: 10.1080/10245330701562634. Hematology. 2007. PMID: 17852463 Review.
Cited by
- Dense deposit disease in Korean children: a multicenter clinicopathologic study.
Park SJ, Kim YJ, Ha TS, Lim BJ, Jeong HJ, Park YH, Lee DY, Kim PK, Kim KS, Chung WY, Shin JI. Park SJ, et al. J Korean Med Sci. 2012 Oct;27(10):1215-21. doi: 10.3346/jkms.2012.27.10.1215. Epub 2012 Oct 2. J Korean Med Sci. 2012. PMID: 23091320 Free PMC article. - Advances in haematological pharmacotherapy in 21st century.
Ghosh K, Ghosh K. Ghosh K, et al. Indian J Hematol Blood Transfus. 2010 Jun;26(2):30-40. doi: 10.1007/s12288-010-0019-1. Epub 2010 Sep 28. Indian J Hematol Blood Transfus. 2010. PMID: 21629633 Free PMC article. - Terminal complement inhibition dampens the inflammation during COVID-19.
Kulasekararaj AG, Lazana I, Large J, Posadas K, Eagleton H, Lord Villajin J, Zuckerman M, Gandhi S, Marsh JCW. Kulasekararaj AG, et al. Br J Haematol. 2020 Aug;190(3):e141-e143. doi: 10.1111/bjh.16916. Epub 2020 Jun 28. Br J Haematol. 2020. PMID: 32495372 Free PMC article. No abstract available. - Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.
Hsiung CC, Wilson CM, Sambold NA, Dai R, Chen Q, Teyssier N, Misiukiewicz S, Arab A, O'Loughlin T, Cofsky JC, Shi J, Gilbert LA. Hsiung CC, et al. Nat Biotechnol. 2024 May 17. doi: 10.1038/s41587-024-02224-0. Online ahead of print. Nat Biotechnol. 2024. PMID: 38760567 - Anti-inflammatory interventions-what has worked, not worked, and what may work in the future.
Fattahi F, Ward PA. Fattahi F, et al. Transl Res. 2016 Jan;167(1):1-6. doi: 10.1016/j.trsl.2015.08.003. Epub 2015 Aug 14. Transl Res. 2016. PMID: 26323016 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous