Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria

Peter Hillmen, Petra Muus, Ulrich Dührsen, Antonio M. Risitano, Jörg Schubert, Lucio Luzzatto, Hubert Schrezenmeier, Jeffrey Szer, Robert A. Brodsky, Anita Hill, Gerard Socié, Monica Bessler, Scott A. Rollins, Leonard Bell, Russell P. Rother, Neal S. Young

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Abstract

Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated whether long-term treatment with the complement inhibitor eculizumab reduces the rate of TE in patients with PNH. Clinical trial participants included all patients in the 3 eculizumab PNH clinical studies, which recruited patients between 2002 and 2005 (n = 195); patients from these studies continued treatment in the current multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared with the pretreatment rate in the same patients. The TE event rate with eculizumab treatment was 1.07 events/100 patient-years compared with 7.37 events/100 patient-years (P < .001) prior to eculizumab treatment (relative reduction, 85%; absolute reduction, 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TE events were reduced from 39 events before eculizumab to 3 events during eculizumab (P < .001). The TE event rate in antithrombotic-treated patients (n = 103) was reduced from 10.61 to 0.62 events/100 patient-years with eculizumab treatment (P < .001). These results show that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. This study is registered at http://clinicaltrials.gov (study ID no. NCT00122317).

Original languageEnglish (US)
Pages (from-to)4123-4128
Number of pages6
JournalBlood
Volume110
Issue number12
DOIs
StatePublished - Dec 1 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Hillmen, P., Muus, P., Dührsen, U., Risitano, A. M., Schubert, J., Luzzatto, L., Schrezenmeier, H., Szer, J., Brodsky, R. A., Hill, A., Socié, G., Bessler, M., Rollins, S. A., Bell, L., Rother, R. P., & Young, N. S. (2007). Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood, 110(12), 4123-4128. https://doi.org/10.1182/blood-2007-06-095646