Sarah C Grünert1, Terry G J Derks2, Katarina Adrian3, Khalid Al-Thihli4, Diana Ballhausen5, Joanna Bidiuk6, Andrea Bordugo7, Monica Boyer8, Drago Bratkovic9, Michaela Brunner-Krainz10, Alberto Burlina11, Anupam Chakrapani12, Willemijn Corpeleijn13, Alison Cozens14, Charlotte Dawson15, Helena Dhamko16, Maja Djordjevic Milosevic17, Hernan Eiroa18, Yael Finezilber19, Carolina Fischinger Moura de Souza20, Maria Concepción Garcia-Jiménez21, Serena Gasperini22, Dorothea Haas23, Johannes Häberle24, Rebecca Halligan25, Law Hiu Fung26, Alexandra Hörbe-Blindt27, Laura Maria Horka28, Martina Huemer29, Sema Kalkan Uçar30, Bozica Kecman17, Sebile Kilavuz31, Gergely Kriván32, Martin Lindner33, Natalia Lüsebrink33, Konstantinos Makrilakis34, Anne Mei-Kwun Kwok35, Esther M Maier36, Arianna Maiorana37, Shawn E McCandless38, John James Mitchell39, Hiroshi Mizumoto40, Helen Mundy41, Carlos Ochoa42, Kathryn Pierce43, Pilar Quijada Fraile44, Debra Regier45, Alessandro Rossi46, René Santer47, Hester C Schuman48, Piotr Sobieraj6, Johannes Spenger49, Ronen Spiegel50, Karolina M Stepien51, Galit Tal52, Mojca Zerjav Tanšek53, Ana Drole Torkar53, Michel Tchan54, Santhosh Thyagu16, Samantha A Schrier Vergano55, Erika Vucko56, Natalie Weinhold57, Petra Zsidegh58, Saskia B Wortmann59. 1. Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Centre-University of Freiburg, Faculty of Medicine, Freiburg, Germany. Electronic address: sarah.gruenert@uniklinik-freiburg.de. 2. Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands. 3. Department of Pediatrics, Queen Silvias Childrens Hospital, Sahlgrenska University Hospital, Göteborg, Sweden. 4. Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman. 5. Pediatric Metabolic Unit, Pediatrics, Woman-Mother-Child Department, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 6. Department of Internal Medicine, Hypertension and Vascular Diseases, Medical University of Warsaw, Warsaw, Poland. 7. Inherited Metabolic Disease Unit, Pediatric Clinic C, Woman and Child Department, Azienda Ospedaliera Università Integrata, Verona, Italy. 8. Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA. 9. Metabolic Clinic, Women's and Children's Hospital, North Adelaide, South Australia, Australia. 10. University Children's Hospital Graz, Graz, Austria. 11. Division of Inherited Metabolic Diseases, Department of Diagnostic Services, University Hospital, Padua, Italy. 12. Department of Metabolic Medicine, Great Ormond Street Hospital, London, United Kingdom. 13. Department of Pediatrics, Division of Metabolic Disorders, Emma Children's Hospital, Gastroenterology, Endocrinology & Metabolism, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 14. Royal Hospital for Children and Young People, Edinburgh, United Kingdom. 15. Department of Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham, Birmingham, United Kingdom. 16. Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 17. Metabolic and Genetic Department, Mother and Child Health Care Institute of Serbia "Dr Vukan Čupić", Belgrade, Serbia. 18. Servicio de Errores Congenitos del Metabolismo, Hospital de Pediatria "J.P. Garrahan", Buenos Aires, Argentina. 19. Metabolic Diseases Unit and Internal Medicine Department A, Sheba Medical Center, Ramat Gan, Israel. 20. Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. 21. Neurometabolic Unit, Pediatric Department, Miguel Servet Universitary Hospital, Zaragoza, Spain. 22. Metabolic Rare Diseases Unit, Paediatric Department, San Gerardo Hospital, Monza, Italy. 23. Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany. 24. Division of Metabolism and Children`s Research Center, University Children's Hospital Zurich, Zürich, Switzerland. 25. Department of Metabolic Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia. 26. Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong Island, Hong Kong. 27. Eltern-Kind-Zentrum Prof. Hess, Medical Centre Bremen Mitte, Bremen, Germany. 28. Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich and University of Zurich, Zurich, Switzerland. 29. Division of Metabolism and Children`s Research Center, University Children's Hospital Zurich, Zürich, Switzerland; Department of Paediatrics, University Children's Hospital Basel and University of Basel, Basel, Switzerland. 30. Division of Metabolism and Nutrition, Department of Pediatrics, Ege University Children's Hospital, Izmir, Turkey. 31. Division of Pediatric Metabolism, Department of Pediatrics, University of Health Sciences, Van Training and Research Hospital, Van, Turkey. 32. Department for Pediatric Hematology and Hemopoietic Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Budapest, Hungary. 33. Department of Pediatric Neurology, University Children's Hospital Frankfurt, Frankfurt, Germany. 34. First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, Athens, Greece. 35. Department of Pediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong. 36. Section of Inborn Errors of Metabolism, Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany. 37. Division of Metabolism, Department of Pediatric Subspecialties, Ospedale Pediatrico Bambino Gesù, Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy. 38. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Department of Genetics and Metabolism, Children's Hospital Colorado, Aurora, CO. 39. Division of Pediatric Endocrinology, McGill University Health Center, Montreal, Quebec, Canada. 40. Department of Pediatrics, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan. 41. Evelina Children's Hospital, London, United Kingdom. 42. Department of Pediatrics, Complejo Asistencial de Zamora, Zamora, Spain. 43. York University, Toronto, Ontario, Canada. 44. Reference Center for Inherited Metabolic Disorders, Department of Pediatrics, Hospital Universitario 12 de Octubre, Madrid, Spain. 45. Genetics and Metabolism, Children's National Hospital, Washington DC. 46. Section of Paediatrics, Department of Translational Medicine, University of Naples "Federico II", Naples, Italy. 47. Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany. 48. Mediclinic Kloof Hospital, Pretoria, South Africa. 49. University Children's Hospital Salzburg, Salzburg, Austria. 50. Pediatric Department B, Emek Medical Center, Afula, Rappaport School of Medicine, Technion, Haifa, Israel. 51. Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, Salford, United Kingdom. 52. Metabolic Clinic, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel. 53. University Children's Hospital, Department of Endocrinology, Diabetes and Metabolism, Ljubljana University Medical Centre, Ljubljana, Slovenia. 54. Department of Genetic Medicine, Westmead Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. 55. Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, VA. 56. Division of Genetics, Birth Defects, and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. 57. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Center of Chronically Sick Children, Berlin, Germany. 58. Newborn Screening and Metabolic Centre, 1(st) Department of Pediatrics, Semmelweis University, Budapest, Hungary. 59. University Children's Hospital Salzburg, Salzburg, Austria; Amalia Children's Hospital, Nijmegen, The Netherlands.
Abstract
PURPOSE: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib.
PURPOSE: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib.
Authors: David Bick; Arzoo Ahmed; Dasha Deen; Alessandra Ferlini; Nicolas Garnier; Dalia Kasperaviciute; Mathilde Leblond; Amanda Pichini; Augusto Rendon; Aditi Satija; Alice Tuff-Lacey; Richard H Scott Journal: Int J Neonatal Screen Date: 2022-07-15