Long term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. | Aplastic Anemia and MDS International Foundation

Long term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival.

Journal Title: 
Blood
Author(s): 
Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, Mitchell LD, Cohen DR, Gregory WM, Hillmen P.
Primary Author: 
Kelly RJ
Original Publication Date: 
Friday, April 1, 2011

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder with increased mortality and morbidity due to intense intravascular hemolysis. Eculizumab, a monoclonal antibody against the complement protein C5, stops the intravascular hemolysis in PNH. We evaluated 79 consecutive patients treated with eculizumab in Leeds between May 2002 and July 2010. Mortality and disease symptoms were studied. The survival of the 79 patients treated with eculizumab was not different to an age and sex matched normal control population (p=0.46) but was significantly better than 30 similar patients with PNH managed in the 7 years before eculizumab (p=0.030). Three patients on eculizumab, all over 50 years old, died from causes unrelated to PNH. Twenty-one of the 79 patients (27%) had a thrombosis prior to starting eculizumab (5.6 events per 100 patient years) compared with 2 thrombotic episodes on eculizumab (0.8 events per 100 patient years; p<0.001). Twenty-one patients with no prior history of thrombosis discontinued warfarin after starting eculizumab with no thrombotic sequelae. Forty of 61 (66%) patients on treatment for over 12 months achieved transfusion independence on eculizumab. The mean transfusion requirement reduced by 74% falling from 19.3 units in the 12 month period immediately prior to commencing eculizumab to 5.0 units in the most recent 12 months on eculizumab in these 61 patients (p<0.001). Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it is equivalent to that of the general population.