Yiting Cai, Baojing Liu, Lizhi Chen, Lu Zhang, Kejing Tang, Xiaoyun Jiang, Pan Chen
{"title":"优化霉酚酸暴露降低儿科肾病综合征复发风险：一项观察性队列研究。","authors":"Yiting Cai, Baojing Liu, Lizhi Chen, Lu Zhang, Kejing Tang, Xiaoyun Jiang, Pan Chen","doi":"10.1002/bcp.70307","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Mycophenolic acid (MPA) effectively reduces relapse in paediatric nephrotic syndrome (NS), yet its pharmacokinetic variability hinders optimal dosing. This study aimed to define risk reference values of MPA area under the concentration-time curve (AUC<sub>0-12h</sub>) for relapse prevention during maintenance therapy.</p><p><strong>Methods: </strong>In this retrospective cohort study, 89 paediatric NS patients receiving MPA were enrolled. Factors influencing relapse were evaluated via binary logistic regression. Optimal cut-off threshold were determined using receiver operating characteristic (ROC) curves, while Kaplan-Meier and Cox regression analyses assessed relapse-free survival (RFS).</p><p><strong>Results: </strong>Lower MPA AUC<sub>0-12h</sub> levels strongly correlated with relapse (relapse group: 31.49 vs. non-relapse: 36.48 μg/h/mL, P < 0.001). Logistic regression confirmed MPA AUC<sub>0-12h</sub> as a protective factor (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99). ROC analysis identified 31.51 μg/h/mL as the optimal risk reference value (sensitivity = 87.5%, specificity = 51.02%). Cox regression further demonstrated subthreshold exposure as an independent relapse risk (hazard ratio [HR] = 0.24, 95% CI: 0.14-0.43, P < 0.001). Subgroup analyses validated this risk reference value across corticosteroid response, relapse frequency and rituximab use, though not in focal segmental glomerulosclerosis.</p><p><strong>Conclusions: </strong>Maintaining MPA AUC<sub>0-12h</sub> ≥ 31.51 μg/h/mL significantly reduces relapse risk in paediatric NS. Individualized mycophenolate mofetil (MMF) dosing guided by therapeutic drug monitoring is critical for optimizing outcomes.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Optimizing mycophenolic acid exposure for reduced relapse risk in paediatric nephrotic syndrome: An observational cohort study.\",\"authors\":\"Yiting Cai, Baojing Liu, Lizhi Chen, Lu Zhang, Kejing Tang, Xiaoyun Jiang, Pan Chen\",\"doi\":\"10.1002/bcp.70307\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Mycophenolic acid (MPA) effectively reduces relapse in paediatric nephrotic syndrome (NS), yet its pharmacokinetic variability hinders optimal dosing. This study aimed to define risk reference values of MPA area under the concentration-time curve (AUC<sub>0-12h</sub>) for relapse prevention during maintenance therapy.</p><p><strong>Methods: </strong>In this retrospective cohort study, 89 paediatric NS patients receiving MPA were enrolled. Factors influencing relapse were evaluated via binary logistic regression. Optimal cut-off threshold were determined using receiver operating characteristic (ROC) curves, while Kaplan-Meier and Cox regression analyses assessed relapse-free survival (RFS).</p><p><strong>Results: </strong>Lower MPA AUC<sub>0-12h</sub> levels strongly correlated with relapse (relapse group: 31.49 vs. non-relapse: 36.48 μg/h/mL, P < 0.001). Logistic regression confirmed MPA AUC<sub>0-12h</sub> as a protective factor (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99). ROC analysis identified 31.51 μg/h/mL as the optimal risk reference value (sensitivity = 87.5%, specificity = 51.02%). Cox regression further demonstrated subthreshold exposure as an independent relapse risk (hazard ratio [HR] = 0.24, 95% CI: 0.14-0.43, P < 0.001). Subgroup analyses validated this risk reference value across corticosteroid response, relapse frequency and rituximab use, though not in focal segmental glomerulosclerosis.</p><p><strong>Conclusions: </strong>Maintaining MPA AUC<sub>0-12h</sub> ≥ 31.51 μg/h/mL significantly reduces relapse risk in paediatric NS. Individualized mycophenolate mofetil (MMF) dosing guided by therapeutic drug monitoring is critical for optimizing outcomes.</p>\",\"PeriodicalId\":9251,\"journal\":{\"name\":\"British journal of clinical pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British journal of clinical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/bcp.70307\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British journal of clinical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/bcp.70307","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Optimizing mycophenolic acid exposure for reduced relapse risk in paediatric nephrotic syndrome: An observational cohort study.
Aims: Mycophenolic acid (MPA) effectively reduces relapse in paediatric nephrotic syndrome (NS), yet its pharmacokinetic variability hinders optimal dosing. This study aimed to define risk reference values of MPA area under the concentration-time curve (AUC0-12h) for relapse prevention during maintenance therapy.
Methods: In this retrospective cohort study, 89 paediatric NS patients receiving MPA were enrolled. Factors influencing relapse were evaluated via binary logistic regression. Optimal cut-off threshold were determined using receiver operating characteristic (ROC) curves, while Kaplan-Meier and Cox regression analyses assessed relapse-free survival (RFS).
Results: Lower MPA AUC0-12h levels strongly correlated with relapse (relapse group: 31.49 vs. non-relapse: 36.48 μg/h/mL, P < 0.001). Logistic regression confirmed MPA AUC0-12h as a protective factor (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99). ROC analysis identified 31.51 μg/h/mL as the optimal risk reference value (sensitivity = 87.5%, specificity = 51.02%). Cox regression further demonstrated subthreshold exposure as an independent relapse risk (hazard ratio [HR] = 0.24, 95% CI: 0.14-0.43, P < 0.001). Subgroup analyses validated this risk reference value across corticosteroid response, relapse frequency and rituximab use, though not in focal segmental glomerulosclerosis.
Conclusions: Maintaining MPA AUC0-12h ≥ 31.51 μg/h/mL significantly reduces relapse risk in paediatric NS. Individualized mycophenolate mofetil (MMF) dosing guided by therapeutic drug monitoring is critical for optimizing outcomes.
期刊介绍：
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.
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