Kazuki Tanaka1, Brigitte Adams2, Alvaro Madrid Aris3, Naoya Fujita4, Masayo Ogawa5, Stephan Ortiz5, Marc Vallee5, Larry A Greenbaum6. 1. Department of Nephrology, Aichi Children's Health and Medical Center, 7-426, Morioka-cho, Obu City, Aichi prefecture, 474-8710, Japan. kazuki.tanaka0505@gmail.com. 2. Department of Pediatric Nephrology, Children's Hospital Queen Fabiola, Université libre de Bruxelles, Brussels, Belgium. 3. Children's Nephrology and Renal Transplantation Service, Children's Maternity Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain. 4. Department of Nephrology, Aichi Children's Health and Medical Center, 7-426, Morioka-cho, Obu City, Aichi prefecture, 474-8710, Japan. 5. Alexion Pharmaceuticals Inc, Boston, MA, USA. 6. Division of Pediatric Nephrology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Abstract
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, a long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report outcomes from a pediatric patient cohort from the ravulizumab clinical trial (NCT03131219) who were switched from chronic eculizumab to ravulizumab treatment. METHODS: Ten patients received a loading dose of ravulizumab on Day 1, followed by maintenance doses administered initially on Day 15, and then, every 4-8 weeks thereafter, depending on body weight. All patients completed the initial evaluation period of 26 weeks and entered the extension period. RESULTS: No patients required dialysis at any point throughout the study. The median estimated glomerular filtration rate values remained stable during the trial: 99.8 mL/min/1.73m2 at baseline, 93.5 mL/min/1.73m2 at 26 weeks, and 104 mL/min/1.73m2 at 52 weeks. At last available follow-up, all patients were in the same chronic kidney disease stage as recorded at baseline. Hematologic variables (platelets, lactate dehydrogenase, and hemoglobin) also remained stable throughout the initial evaluation period and up to the last available follow-up. All patients experienced adverse events; the most common were upper respiratory tract infection (40%) and oropharyngeal pain (30%). There were no meningococcal infections reported, no deaths occurred, and no patients discontinued during the study. CONCLUSIONS: Overall, treatment with ravulizumab in pediatric patients with aHUS who were previously treated with eculizumab resulted in stable kidney and hematologic parameters, with no unexpected safety concerns when administered every 4-8 weeks. TRIAL REGISTRATION: Trial identifiers: Trial ID: ALXN1210-aHUS-312 Clinical trials.gov : NCT03131219 EudraCT number: 2016-002499-29 Graphical abstract.
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, a long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report outcomes from a pediatric patient cohort from the ravulizumab clinical trial (NCT03131219) who were switched from chronic eculizumab to ravulizumab treatment. METHODS: Ten patients received a loading dose of ravulizumab on Day 1, followed by maintenance doses administered initially on Day 15, and then, every 4-8 weeks thereafter, depending on body weight. All patients completed the initial evaluation period of 26 weeks and entered the extension period. RESULTS: No patients required dialysis at any point throughout the study. The median estimated glomerular filtration rate values remained stable during the trial: 99.8 mL/min/1.73m2 at baseline, 93.5 mL/min/1.73m2 at 26 weeks, and 104 mL/min/1.73m2 at 52 weeks. At last available follow-up, all patients were in the same chronic kidney disease stage as recorded at baseline. Hematologic variables (platelets, lactate dehydrogenase, and hemoglobin) also remained stable throughout the initial evaluation period and up to the last available follow-up. All patients experienced adverse events; the most common were upper respiratory tract infection (40%) and oropharyngeal pain (30%). There were no meningococcal infections reported, no deaths occurred, and no patients discontinued during the study. CONCLUSIONS: Overall, treatment with ravulizumab in pediatric patients with aHUS who were previously treated with eculizumab resulted in stable kidney and hematologic parameters, with no unexpected safety concerns when administered every 4-8 weeks. TRIAL REGISTRATION: Trial identifiers: Trial ID: ALXN1210-aHUS-312 Clinical trials.gov : NCT03131219 EudraCT number: 2016-002499-29 Graphical abstract.
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