TY - JOUR
T1 - Concomitant Immunosuppressive Therapy and Eculizumab Use in Patients with Paroxysmal Nocturnal Hemoglobinuria
T2 - An International PNH Registry Analysis
AU - Hill, Anita
AU - De Latour, Régis Peffault
AU - Kulasekararaj, Austin G.
AU - Griffin, Morag
AU - Brodsky, Robert A.
AU - MacIejewski, Jaroslaw P.
AU - Marantz, Jing L.
AU - Gustovic, Philippe
AU - Schrezenmeier, Hubert
N1 - Funding Information:
Statistical consultation was provided by Ami Patel, PhD, MPH, of Alexion Pharmaceuticals, Inc., and Ke Zu, PhD, who was an employee of Alexion at the time of the study. Medical writing support was provided by Apurva Davé, PhD, and Amanda Martin, PhD, of Medical Expressions (Chicago, IL, USA), and was funded by Alexion Pharmaceuticals, Inc.
Publisher Copyright:
© 2022 The Author(s). Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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 + 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. Discussion/conclusion: Although some intergroup differences were seen, concomitant eculizumab and IST were safe and effective regardless of treatment sequence.
AB - 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 + 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. Discussion/conclusion: Although some intergroup differences were seen, concomitant eculizumab and IST were safe and effective regardless of treatment sequence.
KW - Aplastic anaemia
KW - Immunotherapy
KW - Paroxysmal nocturnal hemoglobinuria
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85147234929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147234929&partnerID=8YFLogxK
U2 - 10.1159/000526979
DO - 10.1159/000526979
M3 - Article
C2 - 36108594
AN - SCOPUS:85147234929
SN - 0001-5792
VL - 146
SP - 1
EP - 13
JO - Acta haematologica
JF - Acta haematologica
IS - 1
ER -