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:
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Authors | Peter Hillmen, Claire Hall, Judith C W Marsh, Modupe Elebute, Michael P Bombara, Beth E Petro, Matthew J Cullen, Stephen J Richards, Scott A Rollins, Christopher F Mojcik, Russell P Rother |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 350
Issue 6
Pg. 552-9
(Feb 05 2004)
ISSN: 1533-4406 [Electronic] United States |
PMID | 14762182
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2004 Massachusetts Medical Society |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- eculizumab
- L-Lactate Dehydrogenase
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(adverse effects, pharmacology, therapeutic use)
- Antibodies, Monoclonal, Humanized
- Erythrocyte Transfusion
- Female
- Hemoglobinuria
(diagnosis, drug therapy)
- Hemoglobinuria, Paroxysmal
(blood, drug therapy, therapy, urine)
- Hemolysis
(drug effects)
- Humans
- L-Lactate Dehydrogenase
(blood)
- Male
- Middle Aged
- Quality of Life
- Reticulocyte Count
- Urinalysis
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