Review
Pharmacology & Pharmacy
Young-A Heo
Summary: Some monkeys in the Asia-Pacific region have unique physiological characteristics that enable them to release oxygen during the night, enhancing their vitality and adaptation to dark environments.
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.
Letter
Genetics & Heredity
Sugat Adhikari, Surendra Sapkota, Suraj Shrestha, Kshitiz Karki, Anjan Shrestha
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by a mutation in the phosphatidylinositol glycan class-A gene, resulting in uncontrolled complement activation and intravascular hemolysis. Eculizumab, a terminal complement inhibitor, has revolutionized the treatment of PNH but is expensive, posing challenges in low-middle income countries (LMICs) like Nepal. This article discusses potential approaches for PNH treatment in Nepal and other LMICs.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Hematology
Pedro Henrique Prata, Jacques-Emmanuel Galimard, Flore Sicre de Fontbrune, Anna Duval, Paula Vieira Martins, Stephane Roncelin, Pierre-Edouard Debureaux, Anne-Claire Lepretre, Lise Larcher, Rudy Birsen, Ygal Benhamou, Jean Soulier, Gerand Socie, Veronique Fremeaux-Bacchi, Regis Peffault de Latour
Summary: Patients with rare germline CFH variants in PNH are more likely to require transfusion despite treatment with eculizumab. CFH variants are associated with increased transfusion-dependence in PNH patients and may influence the response to eculizumab.
Review
Hematology
Antonio Maria Risitano, Regis Peffault de Latour
Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disease characterized by complement-mediated intravascular hemolysis, severe thrombophilia, and bone marrow failure. Treatment varies depending on the patient's condition, with the anti-C5 monoclonal antibody eculizumab revolutionizing treatment by controlling hemolysis and thrombotic risk effectively. New strategies of complement inhibition are emerging to improve patient outcomes.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Gaby A. M. Eliesen, Joris van Drongelen, Petra H. H. van den Broek, Andrei Sarlea, Olivier W. H. van der Heijden, Saskia Langemeijer, Rick Greupink, Elena B. Volokhina, Frans G. M. Russel
Summary: Eculizumab has been found to cross the placenta to some extent, with therapeutic drug levels observed in cord blood in a single case. In two pregnancies of a paroxysmal nocturnal haemoglobinuria patient receiving 900 mg eculizumab every 2 weeks, maternal, cord, and placental levels of unbound eculizumab, C5, and C5-eculizumab were measured. The levels of unbound eculizumab were higher than C5-eculizumab complexes in the placenta, suggesting selective transport of unbound eculizumab across the placenta.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
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
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.
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)
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)
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)
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
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
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)