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)
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)
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.
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.
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
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)
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
Hematology
Raymond S. M. Wong
Summary: This article reviews multiple clinical studies on the efficacy and safety of pegcetacoplan treatment in adults with PNH. The studies found that pegcetacoplan showed superior improvements in hemoglobin levels and other hematologic parameters, and effectively managed anemia and anemia-related complications.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)
Article
Hematology
Regis Peffault de Latour, Kohei Hosokawa, Antonio Maria Risitano
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure. The introduction of the anti-C5 monoclonal antibody eculizumab has significantly improved treatment outcomes, but it requires lifelong infusion and some patients still experience anemia. New anti-C5 agents and proximal complement inhibitors offer potential alternatives for improving the efficacy of treatment.
SEMINARS IN HEMATOLOGY
(2022)
Review
Medicine, Research & Experimental
Bo Xu
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening blood disease. The new targeted C3 therapy Empaveli (pegcetacoplan) has been approved by the US FDA for adult PNH patients. Pegcetacoplan targets C3 and effectively controls the complement cascade, resulting in improved hemoglobin levels and reduced need for blood transfusions.
CLINICAL AND EXPERIMENTAL MEDICINE
(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)
Review
Medicine, Research & Experimental
Imre Bodo, Ismail Amine, Ana Boban, Horia Bumbea, Alexander Kulagin, Elena Lukina, Agnieszka Piekarska, Irena Preloznik Zupan, Juraj Sokol, Jerzy Windyga, Jaroslav Cermak
Summary: Hemolysis in PNH is complement-mediated due to the lack of complement inhibitors in the cell membranes. To manage PNH, complement inhibition is the best approach. Three complement inhibitors – eculizumab, ravulizumab, and pegcetacoplan – are approved as targeted therapy for PNH. However, current guidelines do not consider the latest clinical trial evidence. Expert recommendations were created to identify specific populations who may benefit from switching to proximal C3 inhibition.
ADVANCES IN THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Ioanna Lazana, Sean Apap Mangion, Selma Babiker, Joanna Large, Roochi Trikha, Mark Zuckerman, Shreyans Gandhi, Austin G. Kulasekararaj
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by hemolysis and thrombosis, with a significant impact on morbidity and mortality. This study investigated the association between respiratory virus infections and breakthrough hemolysis (BTH) in PNH patients on eculizumab treatment. The results indicate that respiratory virus infections pose a significant risk for BTH in PNH patients and highlight the need for regular screening and close monitoring of patients with respiratory symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Antonio M. Risitano, Regis Peffault de Latour, Luana Marano, Camilla Frieri
Summary: The treatment of paroxysmal nocturnal hemoglobinuria (PNH) has been revolutionized by the introduction of the anti-C5 agent eculizumab, but extravascular hemolysis mediated by C3 remains a problem. Compstatin, a peptide that inhibits the complement cascade at the level of C3, has shown promise in improving the clinical response in PNH. Pegcetacoplan, a pegylated form of compstatin, has been evaluated in clinical studies and has shown superior results compared to eculizumab in terms of hemoglobin change and reduction in hemolysis.
SEMINARS IN IMMUNOLOGY
(2022)
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)