Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy.
Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy.
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DOI：
10.7759/cureus.1907
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发表时间：
2017-12-04
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影响因子：
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通讯作者：
Petri M
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作者：
Timlin H;Magder L;Petri M
背景与目的尽管近年来对狼疮性肾炎的治疗取得了进展，如霉酚酸酯（MMF），但终末期肾病的发生率并没有下降。为了深入了解目前实践中活检证实的狼疮性肾炎的临床结局率，我们使用了一个前瞻性队列的新诊断狼疮性肾炎患者，用MMF治疗，并观察他们的结局。方法20例系统性红斑狼疮（SLE）患者在活检确诊为狼疮性肾炎后不久开始接受吗替麦考酚酯治疗。有5例患者为III级，9例为IV级，4例为III-V级，1例为IV-V级，2例为V级狼疮性肾炎。霉酚酸酯的初始剂量为1000 mg，每日两次。如果未观察到改善，则在一个月后将剂量增加至1500 mg，每日两次。我们使用一种适应区间删失数据的方法，估计了开始使用MMF后直到尿蛋白/肌酐达到0.50 g或更低的时间的生存函数。我们还使用先前在临床试验中使用的五组不同的反应标准来评估治疗反应。这些研究包括布里斯托迈尔斯-施贵宝（BMS）、美国风湿病学会（ACR）、利妥昔单抗狼疮肾炎评估（LUNAR）、Aspreva狼疮管理研究（ALMS）和阿巴西普和环磷酰胺联合疗效和安全性研究（ACCESS）。结果我们估计52%的SLE患者在开始霉酚酸酯治疗的51天内尿蛋白达到0.50克（95%可信区间29%-74%），77%的患者在260天内尿蛋白达到0.50克或更少（95%可信区间57%-97%）。90天和180天时的应答概率分别为5%和33%（布里斯托迈尔斯-施贵宝）、26%和57%（美国风湿病学会）以及11%和28%（利妥昔单抗狼疮肾炎评估、Aspreva狼疮管理研究和阿巴西普与环磷酰胺联合疗效和安全性研究）。结论在常规临床实践中，6个月时的完全肾反应范围为28%~ 57%，与随机临床试验的结果相似。无论反应措施如何，完全肾脏反应缓慢，并且根据大多数指标，在诱导治疗6个月结束时仅少数患者达到完全肾脏反应。这表明迫切需要更快，更有效的狼疮性肾炎治疗。
Background and objective The rate of end-stage renal disease from lupus nephritis has not declined, in spite of recent advances in therapeutics, such as mycophenolate mofetil (MMF). To provide insight into rates of the clinical outcomes in current practice after biopsy-proven lupus nephritis, we used a prospective cohort of the patients with newly diagnosed lupus nephritis, treated with MMF and observed their outcomes. Method Twenty systemic lupus erythematosus (SLE) patients who began mycophenolate mofetil shortly after a biopsy-confirmed diagnosis of lupus nephritis were included in the analysis. There were five patients with class III, nine with class IV, four with class III-V, one with class IV-V and two with class V lupus nephritis. The initial dose of mycophenolate mofetil was 1000 mg twice daily. If no improvement was observed, the dose was increased to 1500 mg twice daily after one month. We estimated the survival function for the time until the urine protein/creatinine reached 0.50 grams or less, after starting MMF by using an approach that accommodated interval-censored data. We also evaluated the treatment response using five different sets of criteria for the response that have previously been used in the clinical trials. These included the Bristol Myers-Squibb (BMS), the American College of Rheumatology (ACR), the lupus nephritis assessment with rituximab (LUNAR ), the Aspreva Lupus Management Study (ALMS), and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS). Result We estimated that 52% of the SLE patients reached 0.50 grams of proteinuria within 51 days of starting mycophenolate mofetil (95% confidence interval 29%-74%) and 77% reached 0.50 grams or less within 260 days (95% confidence interval 57%-97%). The probability of response at 90 and 180 days was 5% and 33% (the Bristol Myers-Squibb), 26% and 57% (the American College of Rheumatology), and 11% and 28% (the lupus nephritis assessment with rituximab, the Aspreva Lupus Management Study and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study). Conclusion The complete renal response ranged from 28% to 57% at six months in the routine clinical practice, mirroring the results in randomized clinical trials. Regardless of the response measures, the complete renal response was slow and, by most indices, reached in only a minority of the patients by the end of six months of the induction therapy. This indicates the urgent need for the faster and more effective lupus nephritis treatments.