Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia
BackgroundDexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes (EryDex) was developed as an alternative to standard glucocorticoids in an effort to eliminate chronic steroid toxicity while preserving efficacy. The primary objective of this report is to describe the safety of...
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Frontiers Media S.A.
2025-01-01
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| author | Mary Kay Koenig Vincenzo Leuzzi Riadh Gouider Riadh Gouider Eppie M. Yiu Eppie M. Yiu Barbara Pietrucha Asbjørg Stray-Pedersen Susan L. Perlman Steve Wu Trudy Burgers Rupam Borgohain Rukmini Mridula Kandadai Isabelle Meyts Giorgia Bucciol Anaita Udwadia-Hegde Ravi Yadav Donna Roberts Aaron Dane Maureen Roden Dirk Thye Biljana Horn Howard M. Lederman William P. Whitehouse |
| author_facet | Mary Kay Koenig Vincenzo Leuzzi Riadh Gouider Riadh Gouider Eppie M. Yiu Eppie M. Yiu Barbara Pietrucha Asbjørg Stray-Pedersen Susan L. Perlman Steve Wu Trudy Burgers Rupam Borgohain Rukmini Mridula Kandadai Isabelle Meyts Giorgia Bucciol Anaita Udwadia-Hegde Ravi Yadav Donna Roberts Aaron Dane Maureen Roden Dirk Thye Biljana Horn Howard M. Lederman William P. Whitehouse |
| author_sort | Mary Kay Koenig |
| collection | DOAJ |
| description | BackgroundDexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes (EryDex) was developed as an alternative to standard glucocorticoids in an effort to eliminate chronic steroid toxicity while preserving efficacy. The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia telangiectasia.MethodsThis is a post-hoc analysis of patients treated with EryDex for a minimum of 24 months in two prospective clinical trials. Outcomes include adverse events, growth, hemoglobin and serum iron, glucose levels, HbA1c, CD4+ lymphocytes, and bone mineral density.ResultsSixty-eight patients completed a minimum of 2 years of treatment with EryDex (mean treatment length 39 ± 11 months). Treatment-emergent adverse events (TEAE), reported in 67 (99%) out of 68 patients, were typically mild and did not cause discontinuation of treatment or death. Treatment-related TEAE were noted in 48 (71%) patients. Notable adverse events included transient pruritus reported in 23 (34%) patients and findings of low serum iron reported in 27 (40%) patients, while at baseline one fifth of patients had low serum iron. Anemia was reported in 9 (13%) patients. The mean hemoglobin level changed by −0.8 ± 1.0 g/dL after 6 months of therapy without subsequent decline. Longitudinal height and weight mean z-scores showed minimal change from baseline to month 24 for height (−0.06 ± 0.49), weight (−0.02 ± 0.71), and body mass index (0.03 ± 0.87). The mean bone mineral density (BMD) z-score showed a decline of 0.4 points over the 24 months of treatment. Values for glucose, HbA1c, cortisol, and CD4+ lymphocyte counts did not show clinically significant changes during prolonged treatment with EryDex.ConclusionThe most common treatment-related adverse events were transient infusion-related pruritus and iron deficiency. There was a decline in BMD which could not be distinguished from the natural course of disease. There were no adverse effects on height, weight and body mass index noted, as documented by stable z-scores throughout the 2 years of treatment. Adverse events typically observed with prolonged glucocorticoid use such as Cushingoid features, weight gain, hypertension, hirsutism, diabetes or stunted growth were rarely reported.Clinical trial registrationClinicalTrials.gov, identifiers: NCT02770807 and NCT03563053. |
| format | Article |
| id | doaj-art-595dc18958a648d695b208e7575812ab |
| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj-art-595dc18958a648d695b208e7575812ab2025-01-23T14:34:32ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-01-011510.3389/fneur.2024.15269141526914Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasiaMary Kay Koenig0Vincenzo Leuzzi1Riadh Gouider2Riadh Gouider3Eppie M. Yiu4Eppie M. Yiu5Barbara Pietrucha6Asbjørg Stray-Pedersen7Susan L. Perlman8Steve Wu9Trudy Burgers10Rupam Borgohain11Rukmini Mridula Kandadai12Isabelle Meyts13Giorgia Bucciol14Anaita Udwadia-Hegde15Ravi Yadav16Donna Roberts17Aaron Dane18Maureen Roden19Dirk Thye20Biljana Horn21Howard M. Lederman22William P. Whitehouse23Department of Pediatrics, Division of Child and Adolescent Neurology, University of Texas Health Science Center Houston McGovern Medical School, Houston, TX, United StatesDepartment of Human Neuroscience, Unit of Child Neurology and Psychiatry, University of Rome La Sapienza, Rome, ItalyDepartment of Neurology, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, TunisiaFaculty of Medicine of Tunis, University of Tunis El Manar, Tunis, TunisiaDepartment of Neurology, Royal Children’s Hospital Melbourne, Neuroscience Research, Murdoch Children’s Research Institute, Melbourne, VIC, AustraliaNeuroscience Research, Murdoch Children’s Research Institute, Melbourne, VIC, AustraliaDepartment of Clinical Immunology, The Children’s Memorial Health Institute, Warsaw, PolandNorwegian National Institute Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospitals, Oslo, NorwayDepartment of Neurology, University of California Los Angeles Medical Center UCLA, Los Angeles, CA, United States0Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States1Department of Habilitation, Innlandet Hospital, Ottestad, Norway2Department of Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, India3Parkinson’s Disease and Movement Disorder Research Centre, Citi Neuro Centre, Hyderabad, India4Department of Pediatrics, University Hospitals Leuven and Department of Microbiology Immunology and Transplantation, KU Leuven, Leuven, Belgium4Department of Pediatrics, University Hospitals Leuven and Department of Microbiology Immunology and Transplantation, KU Leuven, Leuven, Belgium5Department of Neurology, Jaslok Hospital and Research Center, Mumbai, India6Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India7GEM Programming Solutions, Macclesfield, United Kingdom8Danestat Consulting Limited, Macclesfield, United Kingdom9Quince Therapeutics, South San Francisco, CA, United States9Quince Therapeutics, South San Francisco, CA, United States9Quince Therapeutics, South San Francisco, CA, United States0Division of Pediatric Allergy and Immunology, Johns Hopkins Hospital, Baltimore, MD, United States1School of Medicine, University of Nottingham, Nottingham, United KingdomBackgroundDexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes (EryDex) was developed as an alternative to standard glucocorticoids in an effort to eliminate chronic steroid toxicity while preserving efficacy. The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia telangiectasia.MethodsThis is a post-hoc analysis of patients treated with EryDex for a minimum of 24 months in two prospective clinical trials. Outcomes include adverse events, growth, hemoglobin and serum iron, glucose levels, HbA1c, CD4+ lymphocytes, and bone mineral density.ResultsSixty-eight patients completed a minimum of 2 years of treatment with EryDex (mean treatment length 39 ± 11 months). Treatment-emergent adverse events (TEAE), reported in 67 (99%) out of 68 patients, were typically mild and did not cause discontinuation of treatment or death. Treatment-related TEAE were noted in 48 (71%) patients. Notable adverse events included transient pruritus reported in 23 (34%) patients and findings of low serum iron reported in 27 (40%) patients, while at baseline one fifth of patients had low serum iron. Anemia was reported in 9 (13%) patients. The mean hemoglobin level changed by −0.8 ± 1.0 g/dL after 6 months of therapy without subsequent decline. Longitudinal height and weight mean z-scores showed minimal change from baseline to month 24 for height (−0.06 ± 0.49), weight (−0.02 ± 0.71), and body mass index (0.03 ± 0.87). The mean bone mineral density (BMD) z-score showed a decline of 0.4 points over the 24 months of treatment. Values for glucose, HbA1c, cortisol, and CD4+ lymphocyte counts did not show clinically significant changes during prolonged treatment with EryDex.ConclusionThe most common treatment-related adverse events were transient infusion-related pruritus and iron deficiency. There was a decline in BMD which could not be distinguished from the natural course of disease. There were no adverse effects on height, weight and body mass index noted, as documented by stable z-scores throughout the 2 years of treatment. Adverse events typically observed with prolonged glucocorticoid use such as Cushingoid features, weight gain, hypertension, hirsutism, diabetes or stunted growth were rarely reported.Clinical trial registrationClinicalTrials.gov, identifiers: NCT02770807 and NCT03563053.https://www.frontiersin.org/articles/10.3389/fneur.2024.1526914/fullataxia telangiectasiadexamethasone sodium phosphate encapsulated in autologous erythrocytessafetyadverse eventsgrowthbone mineral density |
| spellingShingle | Mary Kay Koenig Vincenzo Leuzzi Riadh Gouider Riadh Gouider Eppie M. Yiu Eppie M. Yiu Barbara Pietrucha Asbjørg Stray-Pedersen Susan L. Perlman Steve Wu Trudy Burgers Rupam Borgohain Rukmini Mridula Kandadai Isabelle Meyts Giorgia Bucciol Anaita Udwadia-Hegde Ravi Yadav Donna Roberts Aaron Dane Maureen Roden Dirk Thye Biljana Horn Howard M. Lederman William P. Whitehouse Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia Frontiers in Neurology ataxia telangiectasia dexamethasone sodium phosphate encapsulated in autologous erythrocytes safety adverse events growth bone mineral density |
| title | Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia |
| title_full | Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia |
| title_fullStr | Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia |
| title_full_unstemmed | Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia |
| title_short | Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia |
| title_sort | long term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia |
| topic | ataxia telangiectasia dexamethasone sodium phosphate encapsulated in autologous erythrocytes safety adverse events growth bone mineral density |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1526914/full |
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