Shuichi Ito1, Yoshihiko Hidaka2, Norimitsu Inoue3, Shinya Kaname4, Hideki Kato5, Masanori Matsumoto6, Yoshitaka Miyakawa7, Masashi Mizuno8, Hirokazu Okada9, Akihiko Shimono10, Takahisa Matsuda10, Shoichi Maruyama8, Yoshihiro Fujimura11, Masaomi Nangaku5, Shoji Kagami12. 1. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. itoshu@yokohama-cu.ac.jp. 2. Clinical Division of Pediatrics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. 3. Department of Tumor Immunology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan. 4. Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan. 5. Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 6. Department of Blood Transfusion Medicine, Nara Medical University, 840 Shijyo-cho, Kashihara, Nara, 634-8522, Japan. 7. Department of General Internal Medicine, Thrombosis and Hemostasis Center, Saitama Medical University Hospital, 38 Moroyama, Iruma-gun, Saitama, 350-0495, Japan. 8. Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. 9. Saitama Medical University, 38 Moroyama, Iruma-gun, Saitama, 350-0495, Japan. 10. Alexion Pharma GK, 1-18-14 Ebisu, Shibuya-ku, Tokyo, 150-0013, Japan. 11. Japanese Red Cross Kinki Block Blood Center, 7-5-17, Saitoasagi, Ibaraki, Osaka, 567-0085, Japan. 12. Department of Pediatrics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto cho 3-chome, Tokushima, 770-8503, Japan.
Abstract
BACKGROUND: In 2013, eculizumab was approved for treatment of the atypical hemolytic-uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of "aHUS" to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA. METHODS: Pediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event-free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed. RESULTS: In 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes' variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event-free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported. CONCLUSIONS: This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting.
BACKGROUND: In 2013, eculizumab was approved for treatment of the atypical hemolytic-uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of "aHUS" to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA. METHODS: Pediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event-free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed. RESULTS: In 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes' variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event-free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported. CONCLUSIONS: This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting.
Authors: Raquel Medeiros de Souza; Bernardo Henrique Mendes Correa; Paulo Henrique Moreira Melo; Pedro Antunes Pousa; Tamires Sara Campos de Mendonça; Lucas Gustavo Castelar Rodrigues; Ana Cristina Simões E Silva Journal: Pediatr Nephrol Date: 2022-07-21 Impact factor: 3.651
Authors: Coralina Bernuy-Guevara; Hassib Chehade; Yannick D Muller; Julien Vionnet; François Cachat; Gabriella Guzzo; Carlos Ochoa-Sangrador; F Javier Álvarez; Daniel Teta; Débora Martín-García; Marcel Adler; Félix J de Paz; Frank Lizaraso-Soto; Manuel Pascual; Francisco Herrera-Gómez Journal: Biomedicines Date: 2020-09-16
Authors: Melissa Muff-Luett; Keia R Sanderson; Rachel M Engen; Rima S Zahr; Scott E Wenderfer; Cheryl L Tran; Sheena Sharma; Yi Cai; Susan Ingraham; Erica Winnicki; Donald J Weaver; Tracy E Hunley; Stefan G Kiessling; Meredith Seamon; Robert Woroniecki; Yosuke Miyashita; Nianzhou Xiao; Abiodun A Omoloja; Sarah J Kizilbash; Asif Mansuri; Mahmoud Kallash; Yichun Yu; Ashley K Sherman; Tarak Srivastava; Carla M Nester Journal: Pediatr Nephrol Date: 2021-03-10 Impact factor: 3.714