Article
Hematology
Gloria F. Gerber, Robert A. Brodsky
Summary: This article discusses the theoretical basis and clinical studies of using C3 inhibitors in the treatment of PNH, as well as provides suggestions for treatment sequencing.
Review
Hematology
Austin G. Kulasekararaj, Ioanna Lazana
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by deficiency of GPI-linked complement regulators. Despite the introduction of C5 inhibitors, residual hemolysis still occurs, leading to anemia and transfusion dependency in some patients. The development of longer-acting and subcutaneous formulations of C5 inhibitors, as well as proximal complement inhibitors, have shown promising results in improving hemoglobin levels and reducing hemolysis. Combination treatments have also been explored. This review discusses the current therapeutic options and emerging approaches for PNH.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Hematology
Jens Panse
Summary: In the past 20 years, therapy for paroxysmal nocturnal hemoglobinuria (PNH) mainly relied on antibody-based terminal complement inhibition. PNH is a disease characterized by a mutation that causes the absence or deficiency of complement-regulatory proteins on blood cells, leading to intravascular hemolysis and related complications. Recently, there has been a development of new drugs targeting the proximal and terminal complement cascade, with the approval of the first proximal complement inhibitor targeting C3 in 2021. This article aims to provide an overview of the progress made in PNH treatment and discuss the approved therapeutic options, as well as the potential impact and consequences of current and future treatments on patients' lives.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Medicine, General & Internal
Peter Hillmen, Jeff Szer, Ilene Weitz, Alexander Roeth, Britta Hoechsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos de Castro, Hisakazu Nishimori, Lisa Tan, Mohamed Hamdani, Pascal Deschatelets, Cedric Francois, Federico Grossi, Temitayo Ajayi, Antonio Risitano, Regis Peffault de la Tour
Summary: The study demonstrated that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Hematology
Austin G. Kulasekararaj, Antonio M. Risitano, Jaroslaw P. Maciejewski, Rosario Notaro, Peter Browett, Jong Wook Lee, Mingjun Huang, Michael Geffner, Robert A. Brodsky
Summary: The study showed that adding an oral complement inhibitor danicopan to PNH patients who were dependent on eculizumab led to an increase in Hgb levels, a reduction in blood transfusion requirements, and improvements in fatigue, with good tolerability.
Review
Medicine, General & Internal
Bruno Fattizzo, Fabio Serpenti, Juri Alessandro Giannotta, Wilma Barcellini
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease with ongoing research on its pathophysiology, diagnostics, and treatment. Advanced flow cytometry techniques have enabled detection of small PNH clones, but data interpretation remains challenging. New complement inhibitors may improve patients' quality of life and response rates, but questions regarding their use and long-term safety need further investigation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Patricia Eiko Yamakawa, Ana Rita Fonseca, Ismael Dale Cotrim Guerreiro da Silva, Matheus Vescovi Goncalves, Dirce Maria Marchioni, Antonio Augusto Ferreira Carioca, David Michonneau, Celso Arrais-Rodrigues
Summary: This study aimed to identify the dysfunctional pathways involved in the pathophysiology of PNH by comparing the metabolic profiles of PNH patients to healthy controls, as well as analyzing the metabolomic profiles before and after eculizumab treatment. The results showed significant differences in metabolomes between PNH patients and healthy controls, and eculizumab treatment appeared to improve defects in the Acyl CoA metabolism, reducing oxidative stress and inflammation.
Review
Immunology
Nicole Galli, Loredana Pettine, Mauro Panigada, Laura Daprai, Grazia Suriano, Anna Grancini, Wilma Barcellini, Bruno Fattizzo
Summary: This case report highlights the risk of life-threatening infection by non-groupable Neisseria meningitidis in a young patient with paroxysmal nocturnal haemoglobinuria (PNH) treated with ravulizumab. Prompt diagnosis and treatment are crucial in managing such infections in PNH patients on complement inhibitors.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Hematology
Austin G. Kulasekararaj, Robert A. Brodsky, Jun-ichi Nishimura, Christopher J. Patriquin, Hubert Schrezenmeier
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder that can cause hemolysis, thrombosis, and organ damage. LDH is used as a biomarker for diagnosis. Eculizumab and ravulizumab, inhibitors of the terminal complement component 5 (C5), have shown effectiveness in treating PNH.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)
Review
Immunology
Melissa A. Colden, Sushant Kumar, Bolormaa Munkhbileg, Daria V. Babushok
Summary: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease that involves mutations in a specific gene, leading to hemolysis and abnormal clonal expansion of blood cells. The mechanisms behind this expansion are still debated, but recent advancements in research and technology offer new opportunities for understanding the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Raymond Siu Ming Wong, Juan Ramon Navarro-Cabrera, Narcisa Sonia Comia, Yeow Tee Goh, Henry Idrobo, Daolada Kongkabpan, David Gomez-Almaguer, Mohammed Al-Adhami, Temitayo Ajayi, Paulo Alvarenga, Jessica Savage, Pascal Deschatelets, Cedric Francois, Federico Grossi, Teresita Dumagay
Summary: PNH is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan, the first C3-targeted therapy, has shown superior efficacy and safety compared to supportive care in complement inhibitor-naive patients with PNH, leading to significant stabilization of hemoglobin levels and reduction in lactate dehydrogenase levels.
Article
Hematology
Jun Ho Jang, Lily Wong, Bor-Sheng Ko, Sung-Soo Yoon, Katie Li, Irina Baltcheva, Prasanna Kumar Nidamarthy, Raghav Chawla, Guido Junge, Eng Soo Yap
Summary: Iptacopan is a novel oral inhibitor of complement factor B under development for the treatment of PNH. This phase 2 study evaluated the efficacy and safety of iptacopan in PNH patients with active hemolysis. The results showed that iptacopan effectively reduced LDH levels, improved hemolytic markers, and rapidly increased Hb levels in most patients.
Article
Pharmacology & Pharmacy
Jun-ichi Nishimura, Antoine Soubret, Noriko Arase, Simon Buatois, Masaki Hotta, Jean-Eric Charoin, Yoshikazu Ito, Sasha Sreckovic, Hiroyuki Takamori, Christoph Bucher, Yasutaka Ueda, Jules Hernandez-Sanchez, Keisuke Gotanda, Gregor Jordan, Kenji Shinomiya, Julia Ramos, Jin Seok Kim, Jens Panse, Regis Peffault de Latour, Alexander Roeth, Eiichi Morii, Hubert Schrezenmeier, Yoshitaka Isaka, Simona Sica, Yuzuru Kanakura, Sung-Soo Yoon, Taroh Kinoshita, Ido Paz-Priel, Alexandre Sostelly
Summary: Drug-target-drug complexes (DTDCs) are newly observed phenomena in patients switching from eculizumab to crovalimab. Optimizing crovalimab dosing reduces the proportion of large DTDCs, ensures adequate complement inhibition, and may improve safety.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Hematology
Jong Wook Lee, Morag Griffin, Jin Seok Kim, Lily Wong Lee Lee, Caroline Piatek, Jun-ichi Nishimura, Cynthia Carrillo Infante, Deepak Jain, Peng Liu, Gleb Filippov, Flore Sicre de Fontbrune, Antonio Risitano, Austin G. Kulasekararaj
Summary: This study investigated the efficacy and safety of danicopan as an add-on therapy to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PNH) and clinically significant extravascular haemolysis. The results showed that danicopan significantly improved haemoglobin concentrations in these patients at week 12, and it had a favorable benefit-risk profile without new safety concerns.
LANCET HAEMATOLOGY
(2023)
Article
Hematology
Alexander Roeth, Satoshi Ichikawa, Yoshikazu Ito, Jin Seok Kim, Zsolt Nagy, Naoshi Obara, Jens Panse, Hubert Schrezenmeier, Simona Sica, Juliette Soret, Kensuke Usuki, Sung-Soo Yoon, Nadiesh Balachandran, Muriel Buri, Pontus Lundberg, Himika Patel, Kenji Shinomiya, Alexandre Sostelly, Jun-ichi Nishimura
Summary: This study reports the long-term outcomes of crovalimab in patients with paroxysmal nocturnal haemoglobinuria. The results showed that crovalimab was well tolerated and achieved sustained C5 inhibition, with effective control of intravascular haemolysis, haemoglobin stabilization, and transfusion avoidance.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Letter
Biophysics
G. O'Kane, D. Bracken-Clarke, N. Gardiner, G. Lee, M. Ni Chonghaile, D. Power, P. A. Daly, J. McCaffrey, C. L. Bacon, E. Conneally, C. Flynn, E. Vandenberghe, M. J. Kennedy, P. V. Browne, D. M. O'Donnell, P. J. Hayden
BONE MARROW TRANSPLANTATION
(2016)
Article
Biophysics
M. van Gelder, L. C. de Wreede, M. Bornhaeuser, D. Niederwieser, M. Karas, N. S. Anderson, M. Gramatzki, P. Dreger, M. Michallet, E. Petersen, D. Bunjes, M. Potter, D. Beelen, J. J. Cornelissen, I. Yakoub-Agha, N. H. Russell, J. Finke, H. Schoemans, A. Vitek, A. Urbano-Ispizua, D. Blaise, L. Volin, P. Chevallier, D. Caballero, H. Putter, A. van Biezen, A. Henseler, S. Schoenland, N. Kroeger, J. Schetelig
BONE MARROW TRANSPLANTATION
(2017)
Article
Hematology
Sebastian Giebel, Myriam Labopin, Gerard Socie, Dietrich Beelen, Paul Browne, Liisa Volin, Slawomira Kyrcz-Krzemien, Ibrahim Yakoub-Agha, Mahmoud Aljurf, Depei Wu, Mauricette Michallet, Renate Arnold, Mohamad Mohty, Arnon Nagler
Article
Hematology
Sebastian Giebel, Myriam Labopin, Gerard Socie, Dietrich Beelen, Paul Browne, Liisa Volin, Slawomira Kyrcz-Krzemien, Ibrahim Yakoub-Agha, Mahmoud Aljurf, Depei Wu, Mauricette Michallet, Renate Arnold, Mohamad Mohty, Arnon Nagler
Article
Hematology
Holger W. Auner, Simona Iacobelli, Giulia Sbianchi, Cora Knol-Bout, Didier Blaise, Nigel H. Russell, Jane F. Apperley, David Pohlreich, Paul V. Browne, Guido Kobbe, Cecilia Isaksson, Stig Lenhoff, Christof Scheid, Cyrille Touzeau, Esa Jantunen, Achilles Anagnostopoulos, Ibrahim Yakoub-Agha, Alina Tanase, Nicolaas Schaap, Wieslaw Wiktor-Jedrzejczak, Marta Krejci, Stefan O. Schoenland, Curly Morris, Laurent Garderet, Nicolaus Kroeger
Article
Medicine, General & Internal
E. Elhassadi, R. Flavin, P. Browne, E. Conneally, P. Hayden, F. Quinn, E. Higgins, E. Vandenberghe
IRISH JOURNAL OF MEDICAL SCIENCE
(2017)
Article
Hematology
Holger W. Auner, Simona Iacobelli, Giulia Sbianchi, Cora Knol-Bout, Didier Blaise, Nigel H. Russell, Jane F. Apperley, David Pohlreich, Paul V. Browne, Guido Kobbe, Cecilia Isaksson, Stig Lenhoff, Christof Scheid, Cyrille Touzeau, Esa Jantunen, Achilles Anagnostopoulos, Ibrahim Yakoub-Agha, Alina Tanase, Nicolaas Schaap, Wieslaw Wiktor-Jedrzejczak, Marta Krejci, Stefan O. Schoenland, Curly Morris, Laurent Garderet, Nicolaus Kroeger
Article
Hematology
Firoozeh Sahebi, Simona Iacobelli, Giulia Sbianchi, Linda Koster, Didier Blaise, Peter Remenyi, Nigel H. Russell, Per Ljungman, Guido Kobbe, Jane Apperley, Marek Trneny, Marta Krejci, Wieslaw Wiktor-Jedrzejczak, James F. Sanchez, Nicolaas Schaap, Cecilia Isaksson, Stig Lenhoff, Paul Browne, Christof Scheid, Keith M. O. Wilson, Ibrahim Yakoub-Agha, Soledad Gonzalez Muniz, Stefan Schoenland, Curly Morris, Laurent Garderet, Nicolaus Kroeger
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2018)
Article
Hematology
Charalampia Kyriakou, Ariane Boumendil, Herve Finel, N. N. Norbert Schmitz, Niels Smedegaard Andersen, Didier Blaise, Patrice Chevallier, Paul Browne, Ram Malladi, Dietger Niederwieser, Antonio Pagliuca, Frank Kroschinsky, Silvia Montoto, Peter Dreger
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2019)
Article
Oncology
S. A. Bright, A. J. Byrne, E. Vandenberghe, P. V. Browne, A. M. McElligott, M. J. Meegan, D. C. Williams
Article
Biophysics
Mauricette Michallet, Peter Dreger, Mohamad Sobh, Linda Koster, Jennifer Hoek, Ariane Boumendil, Christof Scheid, Christopher P. Fox, Gerald Wulf, William Krueger, Michel van Gelder, Paolo Corradini, Domenico Russo, Jakob Passweg, Helene Schoemans, Wolfgang Bethge, Nicolaas Schaap, Jan Cornelissen, Paul Browne, Nadira Durakovic, Lutz Muller, Silvia Montoto, Nicolaus Kroger, Johannes Schetelig
BONE MARROW TRANSPLANTATION
(2020)
Letter
Hematology
Helen Fogarty, Liam Townsend, Cliona Ni Cheallaigh, Colm Bergin, Ignacio Martin-Loeches, Paul Browne, Christopher L. Bacon, Richard Gaule, Alexander Gillett, Mary Byrne, Kevin Ryan, Niamh O'Connell, Jamie M. O'Sullivan, Niall Conlon, James S. O'Donnell
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Article
Hematology
Helen Fogarty, Liam Townsend, Cliona Ni Cheallaigh, Colm Bergin, Ignacio Martin-Loeches, Paul Browne, Christopher L. Bacon, Richard Gaule, Alexander Gillett, Mary Byrne, Kevin Ryan, Niamh O'Connell, Jamie M. O'Sullivan, Niall Conlon, James S. O'Donnell
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Article
Immunology
Yasmeen G. Ghnewa, Vincent P. O'Reilly, Elisabeth Vandenberghe, Paul V. Browne, Anthony M. McElligott, Derek G. Doherty
CLINICAL IMMUNOLOGY
(2017)
Article
Hematology
Marc Bierings, Carmem Bonfim, Regis Peffault De latour, Mahmoud Aljurf, Parinda A. Mehta, Cora Knol, Farid Boulad, Abdelghani Tbakhi, Albert Esquirol, Grant McQuaker, Gulsan A. Sucak, Tarek B. Othman, Constantijn J. M. Halkes, Ben Carpenter, Dietger Niederwieser, Marco Zecca, Nicolaus Kroeger, Mauricette Michallet, Antonio M. Risitano, Gerhard Ehninger, Raphael Porcher, Carlo Dufour
BRITISH JOURNAL OF HAEMATOLOGY
(2018)