"Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria".The New England Journal of Medicine. 2006. 355(12):1233-1243.
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In patients with paroxysmal nocturnal hemoglobinuria (PNH), does eculizumab improve hemoglobin stabilization and reduce transfusion requirements?
In patients with PNH, eculizumab significantly stabilized hemoglobin levels, reduced transfusion requirements, improved markers of intravascular hemolysis, and improved quality of life.
PNH is a disease characterized by intravascular hemolysis due to absent GPI-linked proteins leading to anemia and a need for frequent transfusions as well as other complications. Eculizumab, a monoclonal antibody against complement protein C5, inhibits terminal complement activation. The TRIUMPH trial demonstrated that eculizumab effectively stabilized hemoglobin levels without transfusions in 49% of treated patients, significantly reduced the median number of transfused red cell units, and reduced intravascular hemolysis compared to placebo.
There are no direct guidelines outlined within this study. However, based on evidence from this trial, eculizumab may be a recommended treatment option for patients with PNH requiring frequent transfusions.
- Double-blind, randomized, placebo-controlled, multicenter phase 3 trial - N=87 patients with PNH - Eculizumab group (n=43) vs. Placebo group (n=44) - Treatment period of 26 weeks - Two primary endpoints: stabilization of hemoglobin levels without transfusion, number of units of packed red cells transfused - Secondary endpoints included changes in lactate dehydrogenase levels and quality of life measures.
- Adults (≥18 years) with PNH with at least four transfusions in the prior 12 months. - Inclusion: PNH type III erythrocyte proportion ≥ 10%, platelet count ≥100,000/mm3, lactate dehydrogenase ≥1.5 times the upper limit of normal. - Exclusion: Recent investigational drug use, complement deficiency, active bacterial infection, or history of bone marrow transplantation.
- Eculizumab: 600 mg intravenously weekly for 4 weeks, followed by 900 mg at week 5 and then 900 mg biweekly through week 26. - Placebo administered with the same schedule.
#### Primary Outcomes - Stabilization of hemoglobin levels without transfusion: 49% in eculizumab group vs. 0% in placebo (P<0.001). - Units of packed red cells transfused: Median of 0 units in eculizumab group vs. 10 units in placebo (P<0.001).
- Transfusion independence was achieved in 51% with eculizumab vs. 0% with placebo (P<0.001). - 85.8% lower median area under the curve for lactate dehydrogenase in eculizumab group (P<0.001). - FACIT-Fatigue instrument and EORTC QLQ-C30 scores improved significantly from baseline to week 26 compared to placebo (P<0.001).
- Lack of long-term outcome data regarding eculizumab's effect on thrombosis incidence in PNH. - Results may not be generalizable to PNH patients without a history of frequent transfusions.
- Funded by Alexion Pharmaceuticals. - Several authors reported financial relationships with Alexion Pharmaceuticals.
- Supplemental materials and full trial protocol available on study publication page. - Additional research and long-term studies on the use of eculizumab in PNH.