Exposure-response relationship of mycophenolic acid in pediatric lupus nephritis patients receiving multi-target therapy: An observational cohort study

IF 4.6 2区 医学 Q1 RHEUMATOLOGY
Lizhi Chen , Lu Zhang , Baojing Liu , Xiaohong Liu , Zhijun Huang , Kejing Tang , Pan Chen , Xiaoyun Jiang
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引用次数: 0

Abstract

Objective

To establish the effectiveness threshold of mycophenolic acid-area under the concentration-time curve between 0 h and 12 h (MPA-AUC0–12 h) in pediatric lupus nephritis (LN) patients receiving multi-target therapy.

Methods

This observational cohort study enrolled 48 pediatric LN patients treated with mycophenolate mofetil (MMF), tacrolimus, and prednisone. MPA-AUC0–12 h was calculated using concentrations based on a limited sampling strategy. Binary logistic regression analysis was employed to investigate factors influencing efficacy. Receiver operating characteristic analysis was conducted to assess MPA-AUC0–12 h threshold values. The cumulative incidence of renal remission and inactive systemic lupus erythematosus (SLE) over time was evaluated using Kaplan-Meier analysis. The t-test or Mann-Whitney test was utilized for comparisons between two groups of continuous variables.

Results

To achieve renal remission, the MPA-AUC0–12 h threshold at 6 months was determined to be 25.24 μg·h·mL⁻¹, with an area under the ROC curve (AUC) of 0.83 (P = 0.0002). At 12 months, the MPA-AUC threshold decreased to 23.52 μg·h·mL⁻¹, yielding an AUC of 0.89 (P < 0.0001). For inactive SLE, the MPA-AUC0–12 h threshold at 6 months was found to be 31.16 μg·h·mL⁻¹, with an AUC of 0.80 (P = 0.0004), while at 12 months it decreased slightly to 28.87 μg·h·mL⁻¹, resulting in an AUC of 0.82 (P = 0.0012). Patients who reached target thresholds for MPA-AUC0–12 h achieved renal response or inactive SLE more rapidly.

Conclusion

There is a significant correlation between MPA-AUC0–12 h and treatment response in pediatric LN patients receiving multi-target therapy; therefore, it is recommended that MMF dosing be adjusted according to individual MPA-AUC0–12 h levels.

Abstract Image

儿童狼疮性肾炎患者接受多靶点治疗时霉酚酸的暴露-反应关系:一项观察性队列研究
目的建立儿童狼疮性肾炎(LN)患者接受多靶点治疗时0 ~ 12 h浓度-时间曲线下霉酚酸-面积(MPA-AUC0-12 h)的有效阈值。方法本观察性队列研究纳入48例儿童LN患者,接受霉酚酸酯(MMF)、他克莫司和强的松治疗。MPA-AUC0-12 h采用基于有限采样策略的浓度计算。采用二元logistic回归分析探讨影响疗效的因素。进行受试者工作特征分析,评估MPA-AUC0-12 h阈值。使用Kaplan-Meier分析评估肾脏缓解和非活动性系统性红斑狼疮(SLE)随时间的累积发生率。两组连续变量间的比较采用t检验或Mann-Whitney检验。结果6个月时MPA-AUC0-12 h阈值为25.24 μg·h·mL毒血症,ROC曲线下面积(AUC)为0.83 (P = 0.0002)。在12个月时,MPA-AUC阈值下降到23.52 μg·h·mL⁻,AUC为0.89 (P <;0.0001)。对于不活跃的SLE, 6个月时的MPA-AUC0-12 h阈值为31.16 μg·h·mL毒血症,AUC为0.80 (P = 0.0004); 12个月时的MPA-AUC0-12 h阈值为28.87 μg·h·mL毒血症,AUC为0.82 (P = 0.0012)。MPA-AUC0-12 h达到目标阈值的患者更迅速地获得肾反应或非活动性SLE。结论接受多靶点治疗的小儿LN患者MPA-AUC0-12 h与治疗反应有显著相关性;因此,建议根据个体MPA-AUC0-12 h水平调整MMF剂量。
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来源期刊
CiteScore
9.20
自引率
4.00%
发文量
176
审稿时长
46 days
期刊介绍: Seminars in Arthritis and Rheumatism provides access to the highest-quality clinical, therapeutic and translational research about arthritis, rheumatology and musculoskeletal disorders that affect the joints and connective tissue. Each bimonthly issue includes articles giving you the latest diagnostic criteria, consensus statements, systematic reviews and meta-analyses as well as clinical and translational research studies. Read this journal for the latest groundbreaking research and to gain insights from scientists and clinicians on the management and treatment of musculoskeletal and autoimmune rheumatologic diseases. The journal is of interest to rheumatologists, orthopedic surgeons, internal medicine physicians, immunologists and specialists in bone and mineral metabolism.
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