Oral Iptacopan Monotherapy in Paroxysmal ...
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Article dans une revue scientifique: Article original
DOI :
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Title :
Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria.
Author(s) :
Peffault De Latour, R. [Auteur]
Röth, A. [Auteur]
Kulasekararaj, A. G. [Auteur]
Han, B. [Auteur]
Scheinberg, P. [Auteur]
Maciejewski, J. P. [Auteur]
Ueda, Y. [Auteur]
De Castro, C. M. [Auteur]
Di Bona, E. [Auteur]
Fu, R. [Auteur]
Zhang, L. [Auteur]
Griffin, M. [Auteur]
Langemeijer, S. M. C. [Auteur]
Panse, J. [Auteur]
Schrezenmeier, H. [Auteur]
Barcellini, W. [Auteur]
Mauad, V. A. Q. [Auteur]
Schafhausen, P. [Auteur]
Tavitian, S. [Auteur]
Beggiato, E. [Auteur]
Chew, L. P. [Auteur]
Gaya, A. [Auteur]
Huang, W. H. [Auteur]
Jang, J. H. [Auteur]
Kitawaki, T. [Auteur]
Kutlar, A. [Auteur]
Notaro, R. [Auteur]
Pullarkat, V. [Auteur]
Schubert, J. [Auteur]
Terriou, Louis [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Uchiyama, M. [Auteur]
Wong Lee Lee, L. [Auteur]
Yap, E. S. [Auteur]
Sicre De Fontbrune, F. [Auteur]
Marano, L. [Auteur]
Alashkar, F. [Auteur]
Gandhi, S. [Auteur]
Trikha, R. [Auteur]
Yang, C. [Auteur]
Liu, H. [Auteur]
Kelly, R. J. [Auteur]
Höchsmann, B. [Auteur]
Kerloeguen, C. [Auteur]
Banerjee, P. [Auteur]
Levitch, R. [Auteur]
Kumar, R. [Auteur]
Wang, Z. [Auteur]
Thorburn, C. [Auteur]
Maitra, S. [Auteur]
Li, S. [Auteur]
Verles, A. [Auteur]
Dahlke, M. [Auteur]
Risitano, A. M. [Auteur]
Röth, A. [Auteur]
Kulasekararaj, A. G. [Auteur]
Han, B. [Auteur]
Scheinberg, P. [Auteur]
Maciejewski, J. P. [Auteur]
Ueda, Y. [Auteur]
De Castro, C. M. [Auteur]
Di Bona, E. [Auteur]
Fu, R. [Auteur]
Zhang, L. [Auteur]
Griffin, M. [Auteur]
Langemeijer, S. M. C. [Auteur]
Panse, J. [Auteur]
Schrezenmeier, H. [Auteur]
Barcellini, W. [Auteur]
Mauad, V. A. Q. [Auteur]
Schafhausen, P. [Auteur]
Tavitian, S. [Auteur]
Beggiato, E. [Auteur]
Chew, L. P. [Auteur]
Gaya, A. [Auteur]
Huang, W. H. [Auteur]
Jang, J. H. [Auteur]
Kitawaki, T. [Auteur]
Kutlar, A. [Auteur]
Notaro, R. [Auteur]
Pullarkat, V. [Auteur]
Schubert, J. [Auteur]
Terriou, Louis [Auteur]

Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Uchiyama, M. [Auteur]
Wong Lee Lee, L. [Auteur]
Yap, E. S. [Auteur]
Sicre De Fontbrune, F. [Auteur]
Marano, L. [Auteur]
Alashkar, F. [Auteur]
Gandhi, S. [Auteur]
Trikha, R. [Auteur]
Yang, C. [Auteur]
Liu, H. [Auteur]
Kelly, R. J. [Auteur]
Höchsmann, B. [Auteur]
Kerloeguen, C. [Auteur]
Banerjee, P. [Auteur]
Levitch, R. [Auteur]
Kumar, R. [Auteur]
Wang, Z. [Auteur]
Thorburn, C. [Auteur]
Maitra, S. [Auteur]
Li, S. [Auteur]
Verles, A. [Auteur]
Dahlke, M. [Auteur]
Risitano, A. M. [Auteur]
Journal title :
New England Journal of Medicine
Abbreviated title :
N Engl J Med
Volume number :
390
Pages :
994-1008
Publication date :
2024-03-14
ISSN :
1533-4406
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Background
Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. ...
Show more >Background Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients. Methods In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5–treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. Results In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5–treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5–treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan. Conclusions Iptacopan treatment improved hematologic and clinical outcomes in anti-C5–treated patients with persistent anemia — in whom iptacopan showed superiority to anti-C5 therapy — and in patients who had not received complement inhibitors.Show less >
Show more >Background Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients. Methods In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5–treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. Results In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5–treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5–treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan. Conclusions Iptacopan treatment improved hematologic and clinical outcomes in anti-C5–treated patients with persistent anemia — in whom iptacopan showed superiority to anti-C5 therapy — and in patients who had not received complement inhibitors.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-05-06T21:37:04Z
2024-09-11T08:55:22Z
2024-09-11T08:55:22Z