Mycophenolic acid area under the concentration-time curve is associated with therapeutic response in childhood-onset lupus nephritis
| Autor: | Maud Sordet, Vincent Guigonis, Jérôme Harambat, Marc Fila, Jean-Baptiste Woillard, Stéphanie Tellier, Denis Morin, Stéphane Decramer, F Saint-marcoux, Astrid Godron-Dubrasquet |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Nephrology
medicine.medical_specialty 030232 urology & nephrology Lupus nephritis 030204 cardiovascular system & hematology Mycophenolate Gastroenterology Mycophenolic acid 03 medical and health sciences 0302 clinical medicine Internal medicine Biopsy medicine Humans Child Retrospective Studies Proteinuria medicine.diagnostic_test business.industry Retrospective cohort study Mycophenolic Acid medicine.disease Lupus Nephritis Therapeutic drug monitoring Area Under Curve Pediatrics Perinatology and Child Health Drug Monitoring medicine.symptom business Immunosuppressive Agents medicine.drug |
| Zdroj: | Pediatric Nephrology. 36:341-347 |
| ISSN: | 1432-198X 0931-041X |
| Popis: | Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used in lupus nephritis treatment. Therapeutic drug monitoring of adults suggests that area under the concentration-time curve (AUC) of MPA (MPA-AUC) is associated with clinical outcomes, but childhood data are scarce.Retrospective study of 27 children with biopsy-proven lupus nephritis treated with MMF between 2008 and 2016. In 25 children, MPA-AUC was performed within 6 months after kidney biopsy and MMF initiation. Treatment response at 6 months was defined as normal or improved GFR by 25% compared with baseline, 50% reduction of proteinuria to 0.5 g/day or 50 mg/mmol, and no hematuria.A total of 62 MPA-AUC were analyzed in 27 patients. Overall median was 44 mg h/L (interquartile range [IQR] 33-54). Individual dose adaptation was required in 32 cases (52%) to achieve target AUC of 30-60 mg h/L. At 6 months, 14/25 patients were defined as responders (56%, median MPA-AUC 49 mg h/L (40-59)) and 11/25 as non-responders (44%, 29 mg h/L (24-38)). Patients with MPA-AUC levels 45, 30-45, and 30 mg h/L had 6-month response rates of 89% (8/9), 60% (6/10), and 0% (0/6), respectively. In a logistic regression model adjusted for age, sex, lupus nephritis classification, and time since MMF initiation, an MPA-AUC 45 mg h/L was significantly associated with therapeutic response (OR 3.6, 95% CI 2.4-9.5, p = 0.03).Therapeutic drug monitoring leading to individualized dosing may improve efficacy of MMF. MPA-AUC 45 mg h/L is associated with better response rate and may be considered as a target value in pediatric lupus nephritis. |
| Databáze: | OpenAIRE |
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