VIENNA—Long-term treatment with eculizumab, a recombinant humanized monoclonal antibody, significantly reduces the risk of thrombosis in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to the results of a recent multicenter study.
Peter Hillmen, MD, of the Leeds Teaching Hospitals NHS Trust, reported the results of the study at the 12th Congress of the European Hematology Association in June 2007.
Dr Hillmen and colleagues prospectively examined the aggregate thromboembolism (TE) event rate in eculizumab-treated patients from 3 recent parent studies, as well as a subsequent common extension study. They compared those rates to the TE rate in the same patients’ pre-eculizumab treatment.
Eculizumab, which is designed to inhibit activation of terminal complement components that have been implicated in the development of PNH, reduced the TE rate in each of the three parent studies.
Most importantly, the aggregate TE event rate during eculizumab treatment was significantly reduced by 85% (P=<0.001), when compared with the same patients before eculizumab treatment.
With restriction of the pretreatment observation period to the 12 months immediately preceding eculizumab treatment, the TE event rate during treatment was reduced by 94% (P=0.002). The TE event rate in patients with TE prior to the trials was also reduced by 89% (P=<0.001).
Most TE events prior to eculizumab treatment occurred in patients receiving antithrombotics, either therapeutically or prophylactically. This indicates that the therapy may be insufficient to prevent thrombosis.
Pre-eculizumab treatment, 195 patients experienced 124 TE events. Of the 195 patients, 103 were on antithrombotics.
Of the 103 patients on antithrombotics, there were 54 TE events in 30 patients pre-eculizumab, compared to 1 TE event during eculizumab treatment. This demonstrates that eculizumab significantly reduces the risk of thrombosis in PNH patients, despite treatment with antithrombotics (P=<0.001).
Pre-eculizumab, TE was frequent in patients with lower levels of hemolysis and with mild anemia. Eculizumab significantly reduced TE across these and other subgroups (P=<0.001).
Dr Hillman said these data demonstrate the efficacy of long-term eculizumab treatment in its ability to significantly reduce the occurrence of thrombosis in PNH patients. Because TE accounts for the majority of deaths in PNH, it is reasonable to expect that eculizumab treatment, by decreasing the risk of TE, will increase the life-expectancy in PNH.
PNH is a rare, acquired, and potentially life-threatening disease of the blood characterized by hemolytic anemia, thrombosis, and red-colored urine, resulting from the breakdown of red blood cells.
TE is one of the most feared complications associated with PNH and accounts for approximately 45% of PNH patient deaths. The disease can occur even in individuals who have no previous history of thrombosis.
Patients with PNH are usually treated with anticoagulants on a prophylactic basis. However, these anticoagulants increase the risk of life-threatening hemorrhage without eliminating the potential for thrombosis, which can occur in as many as 30% of the patients who receive anticoagulant treatment.
