Pauline Lancia1, Beate Aurich1, Phuong Ha1, Anne Maisin2, Véronique Baudouin2, Evelyne Jacqz-Aigrain3,4,5. 1. Department of Paediatric Pharmacology and Pharmacogenetics, Hospital Robert Debré, APHP, 48 Boulevard Sérurier, 75019, Paris, France. 2. Department of Paediatric Nephrology, Hospital Robert Debré, APHP, 48 Boulevard Sérurier, 75019, Paris, France. 3. Department of Paediatric Pharmacology and Pharmacogenetics, Hospital Robert Debré, APHP, 48 Boulevard Sérurier, 75019, Paris, France. evelyne.jacqz-aigrain@aphp.fr. 4. Clinical Investigation Center CIC1426, INSERM, Paris, France. evelyne.jacqz-aigrain@aphp.fr. 5. Paris Diderot University, Sorbonne Paris Cité, Paris, France. evelyne.jacqz-aigrain@aphp.fr.
Abstract
BACKGROUND: Progress in immunosuppression has reduced acute rejection, graft loss and mortality after renal transplantation. Adverse drug reactions are well described in adults but few data are available in children. Our objectives were to analyse the adverse events reported in the first 3 years post-transplantation in children receiving tacrolimus or cyclosporine-based immunosuppression and compare them with the information of the Summary of Product Characteristics. METHODS: This retrospective study included all children who underwent a renal transplant at Hospital Robert Debré between 2002 and 2015. Initial immunosuppression was based on induction, calcineurin inhibitor, mycophenolate mofetil and corticosteroids. Adverse events were collected from medical records and coded using the Medical Dictionary for Regulatory Activities and the implications of tacrolimus and cyclosporine analysed. Statistical analyses were performed using SAS 9.4. RESULTS: One hundred and twenty-five children were included. During the observation period [2.7 years (0.6-4.3)], 105 patients received tacrolimus and 39 received cyclosporine. The incidence rate for gastrointestinal disorders was 0.128 and 0.056 by patient-years of exposure (p < 0.05), under tacrolimus and cyclosporine schedules. For neutropenia, it was 0.064 and 0.014 (p < 0.05). The frequencies of toxic nephropathy and gastrointestinal pain were higher than those in the Summary of Product Characteristics of tacrolimus (> 20%) and cyclosporine (> 10%). Cosmetic events for cyclosporine and neutropenia for tacrolimus were frequently observed (18 and 14.3%, respectively), although uncommon in the Summary of Product Characteristics. CONCLUSIONS: The exposure-adjusted incidence rate of gastrointestinal disorders and neutropenia was higher in children under the tacrolimus schedule. Our findings contribute to the evaluation of the benefit-risk balance of immunosuppressive therapy following paediatric renal transplantation.
BACKGROUND: Progress in immunosuppression has reduced acute rejection, graft loss and mortality after renal transplantation. Adverse drug reactions are well described in adults but few data are available in children. Our objectives were to analyse the adverse events reported in the first 3 years post-transplantation in children receiving tacrolimus or cyclosporine-based immunosuppression and compare them with the information of the Summary of Product Characteristics. METHODS: This retrospective study included all children who underwent a renal transplant at Hospital Robert Debré between 2002 and 2015. Initial immunosuppression was based on induction, calcineurin inhibitor, mycophenolate mofetil and corticosteroids. Adverse events were collected from medical records and coded using the Medical Dictionary for Regulatory Activities and the implications of tacrolimus and cyclosporine analysed. Statistical analyses were performed using SAS 9.4. RESULTS: One hundred and twenty-five children were included. During the observation period [2.7 years (0.6-4.3)], 105 patients received tacrolimus and 39 received cyclosporine. The incidence rate for gastrointestinal disorders was 0.128 and 0.056 by patient-years of exposure (p < 0.05), under tacrolimus and cyclosporine schedules. For neutropenia, it was 0.064 and 0.014 (p < 0.05). The frequencies of toxic nephropathy and gastrointestinal pain were higher than those in the Summary of Product Characteristics of tacrolimus (> 20%) and cyclosporine (> 10%). Cosmetic events for cyclosporine and neutropenia for tacrolimus were frequently observed (18 and 14.3%, respectively), although uncommon in the Summary of Product Characteristics. CONCLUSIONS: The exposure-adjusted incidence rate of gastrointestinal disorders and neutropenia was higher in children under the tacrolimus schedule. Our findings contribute to the evaluation of the benefit-risk balance of immunosuppressive therapy following paediatric renal transplantation.
Authors: R Lorho; J Hardwigsen; J Dumortier; G-P Pageaux; F Durand; T Bizollon; A-S Blanc; F Di Giambattista; C Duvoux Journal: Clin Res Hepatol Gastroenterol Date: 2011-05-06 Impact factor: 2.947
Authors: Johannes M M Boots; Maarten H L Christiaans; Elly M Van Duijnhoven; Robert-Jan Van Suylen; Johannes P Van Hooff Journal: Transplantation Date: 2002-12-27 Impact factor: 4.939
Authors: D Antona; A Lepoutre; L Fonteneau; C Baudon; F Halftermeyer-Zhou; Y LE Strat; D Lévy-Bruhl Journal: Epidemiol Infect Date: 2017-02-07 Impact factor: 4.434