"Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria".The New England Journal of Medicine. 2006. 355(12):1233-1243.PubMed•Full text•PDF

### Clinical Question
In patients with paroxysmal nocturnal hemoglobinuria (PNH), does eculizumab improve hemoglobin stabilization and reduce transfusion requirements?

### Bottom Line
In patients with PNH, eculizumab significantly stabilized hemoglobin levels, reduced transfusion requirements, improved markers of intravascular hemolysis, and improved quality of life.

### Major Points


### Guidelines
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.

### Design
- 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.

### Population
- 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.

### Interventions
- 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.

### Outcomes
#### 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).

#### Secondary Outcomes
- 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).

### Criticisms
- 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.

### Funding
- Funded by Alexion Pharmaceuticals.
- Several authors reported financial relationships with Alexion Pharmaceuticals.

### Further Reading
- Supplemental materials and full trial protocol available on study publication page.
- Additional research and long-term studies on the use of eculizumab in PNH.