Tanja Hann、Harim Jang、Yu-Chieh Sung、Chia-Lun Guh、Nicholas M Hiers、Lucille H Tsao、Michelle Luo、Anna Marie Pyle
作者机构
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.
Department of Chemistry, Yale University, New Haven, CT, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Chemistry, Yale University, New Haven, CT, USA. Electronic address: anna.pyle@yale.edu.
Remibrutinib是一种高选择性、强效、共价、可穿透中枢神经系统的口服BTK抑制剂。REMODEL-1和REMODEL-2为两项相同的随机、双盲、双模拟、活性对照、平行组、事件驱动Ⅲ期试验，在46个国家407个中心开展，纳入18-55岁、EDSS评分0-5.5、有近期疾病活动证据的复发型多发性硬化患者，按1:1随机接受口服remibrutinib 100 mg每日两次或特立氟胺14 mg每日一次，主要终点为年化复发率（ARR）。2021年12月13日至2025年12月30日筛查2632例，随机分配2007例；REMODEL-1纳入1000例，REMODEL-2纳入1007例。remibrutinib组ARR显著低于特立氟胺组：REMODEL-1为0.073 vs 0.112（RR 0.648，95%CI 0.453-0.927；p=0.018），REMODEL-2为0.080 vs 0.116（RR 0.688，95%CI 0.487-0.972；p=0.034）。最常见不良事件为上呼吸道感染、鼻咽炎、腹泻和脱发；导致停药的不良事件remibrutinib组较少（3.1% vs 5.8%），安全性与其他适应症一致，无肝脏安全性担忧。研究表明remibrutinib优于特立氟胺且安全性良好，支持其作为复发型多发性硬化潜在新型口服治疗选择。
Department of Neurology and Neurophysiology, University of Freiburg, Freiburg, Germany; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. Electronic address: heinz.wiendl@uniklinik-freiburg.de.
Department of Neurology, Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA.
Turku PET Centre, Clinical Neurosciences and InFLAMES Research Flagship, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland.
Brigham Multiple Sclerosis Center and Division of Neuroimmunology, Mass General Brigham, Boston, MA, USA.
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
Joi Life Wellness Neurology Clinic, Smyrna, GA, USA.
Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.
MedPolonia, Outpatient MS Clinic, Poznań, Poland; Department of Medical Education and Communication, Poznan University of Medical Sciences, Poznań, Poland.
Novartis Pharma, Basel, Switzerland.
Novartis Ireland, Dublin, Ireland.
Novartis Institutes for Biomedical Research, Shanghai, China.
Novartis Pharmaceuticals Corporation, Cambridge, MA, USA.
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain.
Susan DeWolf、Steven J Siegel、Joseph Schmalz、Wael Saber、Alexandre Albanese、Jiayi Dong、Michael J Martens、Brent Logan、Lorenzo Iovino、Kayleigh Ingersoll-Ohmdahl、Nicholas Winn、Edward Chen、James Kaminski、Donna Neuberg、Kyle Hebert、Paula Keskula、Jillian Zavistaski、Lea Steinberg、Isabella Schichter、Zoe Katsamakis、Lorenzo Cagnin、Vanessa Hernandez、Makya Warren、Kristy Applegate、Merav Bar、Saurabh Chhabra、Sung Won Choi、William Clark、Suman Das、Robert Jenq、Richard J Jones、John E Levine、Hemant Murthy、Armin Rashidi、Marcie Riches、Karamjeet Sandhu、Anthony D Sung、Karilyn Larkin、Monzr M Al Malki、Mahasweta Gooptu、Hany Elmariah、Amin Alousi、Lyndsey Runaas、Brian Shaffer、Andrew Rezvani、Najla El Jurdi、Alison W Loren、Danielle Scheffey、Catherine Sanders、Mehdi Hamadani、Jarrod A Dudakov、Stephanie Bien、Harlan Robins、Mary Horowitz、Javier Bolaños-Meade、Shernan Holtan、Ami S Bhatt、Miguel-Angel Perales、Leslie S Kean
作者机构
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pediatrics, Harvard Medical School and Divisions of Infectious Diseases and Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Adaptive Biotechnologies, Seattle, WA, USA.
Department of Medicine, Medical College of Wisconsin and Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI, USA.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
CIBMTR and Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA.
CIBMTR and Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Emmes, Rockville, MD, USA.
Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Division of Hematology-Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Division of Hematology-Oncology and Blood and Marrow Transplant and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL, USA.
CIBMTR, Milwaukee, WI, USA.
Division of Hematologic Malignancies and Cellular Therapy, Kansas University Medical Center, Kansas City, KS, USA.
Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Department of Hematology and Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL, USA.
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center and Department of Immunology, University of Washington, Seattle, WA, USA.
Blood and Marrow Transplantation Section, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Division of Hematology, Departments of Medicine and Genetics, Stanford University, Palo Alto, CA, USA.
Department of Pediatrics, Harvard Medical School, Division of Hematology/Oncology, Boston Children's Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Comparative screening identifies gga-miR-204 as a nutrient-responsive miRNA that targets MAP1LC3B and promotes infectious bursal disease virus replication in HD11 cells.
College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou, Jiangsu, 225009, China. Electronic address: mrrchen@yzu.edu.cn.
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China.
College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou, Jiangsu, 225009, China.
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AI 辅助短评，基于标题和摘要整理该综述聚焦RNA病毒中RNA结构介导的基因调控，整合多病毒家族机制证据并与真核转录组类比，提出RNA结构为基因表达中心调控层。优势在于跨体系视角与机制梳理，但属叙述性综述，未提供系统检索策略或证据分级，病毒与真核间保守性的推断需谨慎解读。对治疗与合成生物学潜力的论述宜视为展望而非已验证结论。