Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria.
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.
Hillmen
Peter
P
Department of Haematology, Leeds Teaching Hospitals National Health Science Trust, Leeds, United Kingdom. peter.hillmen@panp-tr.northy.nhs.uk
Hall
Claire
C
Marsh
Judith C W
JC
Elebute
Modupe
M
Bombara
Michael P
MP
Petro
Beth E
BE
Cullen
Matthew J
MJ
Richards
Stephen J
SJ
Rollins
Scott A
SA
Mojcik
Christopher F
CF
Rother
Russell P
RP
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017707:Erythrocyte Transfusion; D005260:Female; D006456:Hemoglobinuria / Q000175:diagnosis / Q000188:drug therapy; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy* / Q000628:therapy / Q000652:urine; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D017701:Reticulocyte Count; D016482:Urinalysis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab; D007770:L-Lactate Dehydrogenase