Long-term outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in a real-world setting

被引:11
作者
Versmold, Katharina [1 ]
Alashkar, Ferras [1 ]
Raiser, Carina [1 ]
Ofori-Asenso, Richard [2 ]
Xu, Tao [3 ]
Liu, Yutong [4 ]
Katz, Pablo [3 ]
Shang, Aijing [3 ]
Roeth, Alexander [1 ]
机构
[1] Univ Hosp Essen, West German Canc Ctr, Dept Hematol & Stem Cell Transplantat, Essen, Germany
[2] Roche Prod Ltd, Real World Data RWD Enabling Platform, Welwyn Garden City, England
[3] F Hoffmann La Roche Ltd, Basel, Switzerland
[4] Genesis Res, Hoboken, NJ USA
关键词
eculizumab; paroxysmal nocturnal hemoglobinuria; PNH; real-world data; COMPLEMENT INHIBITOR ECULIZUMAB; NATURAL-HISTORY; HEMOLYSIS; EFFICACY; ANEMIA; C5;
D O I
10.1111/ejh.13970
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Describe the real-world clinical profile of eculizumab-treated patients by characterizing their short-and long-term clinical and laboratory outcomes.Methods: This retrospective study used preexisting medical records of eculizumabtreated patients with paroxysmal nocturnal hemoglobinuria (PNH) at the University Hospital Essen. Hematologic response, breakthrough hemolysis, transfusion dependence, and other outcomes were assessed.Results: Of 85 patients with PNH, 76 received eculizumab for =24 weeks (mean follow-up: 5.59 years; total: 425 person-years). At 24 weeks (n = 57 patients with data), 7% and 9% had complete and major hematologic response, respectively. Breakthrough hemolysis occurred in 8%, and 38% required a blood transfusion. Over longterm follow-up (25-264 weeks), 70%-82% of patients did not achieve complete or major hematologic response in any 24-week period. Breakthrough symptoms, breakthrough hemolysis, and transfusion dependence occurred in 63%, 43%, and 63% of patients, respectively, at any point during follow-up. The majority (79%-89%) of patients did not achieve normalized hemoglobin, with 76%-93% having elevated bilirubin or absolute reticulocyte count in any 24-week window. Mean percentage reduction in lactate dehydrogenase (baseline to end of follow-up) was 80.3% (95% CI, 64.0-96.6).Conclusions: A considerable proportion of patients with PNH receiving eculizumab did not achieve optimal clinical outcomes and had an ongoing disease burden.
引用
收藏
页码:84 / 95
页数:12
相关论文
共 34 条
[1]   The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? [J].
Beutler, E ;
Waalen, J .
BLOOD, 2006, 107 (05) :1747-1750
[2]   Characterization of breakthrough hemolysis events observed in the phase III randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria [J].
Brodsky, Robert A. ;
de latour, Regis Peffault ;
Rottinghaus, Scott T. ;
Roeth, Alexander ;
Risitano, Antonio M. ;
Weitz, Ilene C. ;
Hillmen, Peter ;
Maciejewski, Jaroslaw P. ;
Szer, Jeff ;
Lee, Jong Wook ;
Kulasekararaj, Austin G. ;
Volles, Lori ;
Damokosh, Andrew I. ;
Ortiz, Stephan ;
Shafner, Lori ;
Liu, Peng ;
Hillc, Anita ;
Schrezenmeier, Hubert .
HAEMATOLOGICA, 2021, 106 (01) :230-237
[3]   Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population [J].
Cheng, Wendy Y. ;
Sarda, Sujata P. ;
Mody-Patel, Nikita ;
Krishnan, Sangeeta ;
Yenikomshian, Mihran ;
Kunzweiler, Colin ;
Vu, Jensen Duy ;
Cheung, Hoi Ching ;
Duh, Mei Sheng .
CLINICOECONOMICS AND OUTCOMES RESEARCH, 2022, 14 :357-369
[4]   Real-World Healthcare Resource Utilization (HRU) and Costs of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Receiving Eculizumab in a US Population [J].
Cheng, Wendy Y. ;
Sarda, Sujata P. ;
Mody-Patel, Nikita ;
Krishnan, Sangeeta ;
Yenikomshian, Mihran ;
Mahendran, Malena ;
Lejeune, Dominique ;
Yu, Louise H. ;
Duh, Mei Sheng .
ADVANCES IN THERAPY, 2021, 38 (08) :4461-4479
[5]  
Choi CW, 2017, BLOOD RES, V52, P207, DOI 10.5045/br.2017.52.3.207
[6]   Paroxysmal nocturnal hemoglobinuria:: natural history of disease subcategories [J].
de Latour, Regis Peffault ;
Mary, Jean Yves ;
Salanoubat, Celia ;
Terriou, Louis ;
Etienne, Gabriel ;
Mohty, Mohamad ;
Roth, Sophie ;
de Guibert, Sophie ;
Maury, Sebastien ;
Cahn, Jean Yves ;
Socie, Gerard .
BLOOD, 2008, 112 (08) :3099-3106
[7]   Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab [J].
de Latour, Regis Peffault ;
Fremeaux-Bacchi, Veronique ;
Porcher, Raphael ;
Xhaard, Alienor ;
Rosain, Jeremie ;
Castaneda, Diana Cadena ;
Vieira-Martins, Paula ;
Roncelin, Stephane ;
Rodriguez-Otero, Paula ;
Plessier, Aurelie ;
de Fontbrune, Flore Sicre ;
Abbes, Sarah ;
Robin, Marie ;
Socie, Gerard .
BLOOD, 2015, 125 (05) :775-783
[8]   Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study [J].
Debureaux, Pierre-Edouard ;
Kulasekararaj, Austin G. ;
Cacace, Fabiana ;
Silva, Bruno G. P. ;
Calado, Rodrigo T. ;
Barone, Federica ;
Sicre de Fontbrune, Flore ;
Prata, Pedro Henrique ;
Soret, Juliette ;
Sica, Michela ;
Notaro, Rosario ;
Scheinberg, Phillip ;
Mallikarjuna, Vasundhara ;
Gandhi, Shreyans ;
Large, Joanna ;
Risitano, Antonio M. ;
Peffault de Latour, Regis ;
Frieri, Camilla .
BONE MARROW TRANSPLANTATION, 2021, 56 (10) :2600-2602
[9]   Predictors of hemoglobin response to eculizumab therapy in paroxysmal nocturnal hemoglobinuria [J].
DeZern, Amy E. ;
Dorr, Donna ;
Brodsky, Robert A. .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2013, 90 (01) :16-24
[10]   Second-Generation C5 Inhibitors for Paroxysmal Nocturnal Hemoglobinuria [J].
Fattizzo, Bruno ;
Kulasekararaj, Austin G. .
BIODRUGS, 2020, 34 (02) :149-158