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

Introduction: 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. Methods: 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). Results: As of January 1, 2018, 181 Registry-enrolled patients were included in the eculizumab effectiveness analyses (n=138, IST+c-Ecu; n=43, Ecu+cIST); 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. Discussion/conclusion: Although some intergroup differences were seen, concomitant eculizumab and IST was safe and effective regardless of treatment sequence.