Concomitant Immunosuppressive Therapy and Eculizumab Use in Patients with Paroxysmal Nocturnal Hemoglobinuria: An International PNH Registry Analysis

Abstract

<b><i>Introduction:</i></b> Complement C5 inhibitor eculizumab is the first approved treatment for paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disorder caused by uncontrolled terminal complement activation. Approximately 50% of patients with aplastic anemia (AA) have PNH cells. Limited data are available for patients with AA-PNH taking concomitant immunosuppressive therapy (IST) and eculizumab. <b><i>Methods:</i></b> Data from the International PNH Registry (NCT01374360) were used to evaluate the safety and effectiveness of eculizumab and IST in patients taking IST followed by concomitant eculizumab (IST + c-Ecu) or eculizumab followed by concomitant IST (Ecu + c-IST). <b><i>Results:</i></b> As of January 1, 2018, 181 Registry-enrolled patients were included in the eculizumab effectiveness analyses (<i>n</i> = 138, IST + c-Ecu; <i>n</i> = 43, Ecu + c-IST); 87 additional patients received IST alone. Reductions from baseline with eculizumab were observed in the least squares mean lactate dehydrogenase ratio (IST + c-Ecu, −3.4; Ecu + c-IST, −3.5); thrombotic event incidence rates were similar between groups (IST + c-Ecu, 1.3; Ecu + c-IST, 0.7). Red blood cell transfusion rate ratios decreased from baseline for IST + c-Ecu (0.7) and increased for Ecu + c-IST (1.2); there were none for IST alone. Hematological parameters generally improved for IST + c-Ecu and IST alone, and changed minimally or worsened for Ecu + c-IST. Safety signals were generally consistent with those previously described for the respective therapies. <b><i>Discussion/conclusion:</i></b> Although some intergroup differences were seen, concomitant eculizumab and IST were safe and effective regardless of treatment sequence.