Colquitt J L, Kirby J, Green C, Cooper K, Trompeter R S
Southampton Health Technology Assessments Centre, University of Southampton, UK.
Health Technol Assess. 2007;11(21):iii-iv, ix-xi, 1-93. doi: 10.3310/hta11210.
To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS).
Electronic databases from inception to February 2006, bibliographies of studies, and experts in the field.
Studies were selected, quality assessed and data were extracted using recognised methods agreed a priori. Meta-analysis was undertaken where appropriate using the random effects model. Where data allowed, subgroup analysis was undertaken according to renal histopathology.
Two systematic reviews and 11 trials were included in the clinical effectiveness review; however, the quality of reporting and methodology of the included studies was generally poor. No economic evaluations were identified. No statistically significant difference in remission rates was found between cyclophosphamide plus prednisone and prednisone alone for all children or those with focal segmental glomerulosclerosis (FSGS), also the time to response was statistically significantly less with cyclophosphamide (38.4 days versus 95.5 days). Remission rates were not statistically significantly different between intravenous and oral cyclophosphamide. Vomiting was common with intravenous cyclophosphamide, while pneumonia and alopecia occurred in the oral group. Ciclosporin statistically significantly increased the number of children with complete remission compared with placebo or supportive treatment, but not for the FSGS subgroup, adverse effects including infection and hypertension differed little between groups. No differences were found between azathioprine and placebo, with about 13% of each group having remission. Complete or partial remission occurred in six out of seven patients on the 18-month methylprednisolone regimen and three out of five patients on the 6-month regimen, for both groups renal function improved and adverse events such as hypertension and frequent infections occurred. Intravenous dexamethasone and methylprednisolone produced similar complete remission rates, partial remission rates, median time to response (about 10 days) and total number of adverse events, with hypertension as the most common. Six-hour urinary albumin and urinary albumin to creatinine ratio decreased statistically significantly with high-dose but not low-dose enalapril. Tuna fish oil was not associated with any statistically significant improvements in proteinuria, creatinine clearance, serum creatinine or lipid profiles compared with placebo. A very limited literature was found on costs associated with SRNS in children. The pharmaceutical cost of treatment varied considerably: an 8-week course of cyclophosphamide cost less than 6 pounds, while a course of ciclosporin cost almost 900 pounds per year. Treatment with tacrolimus, an alternative to ciclosporin, was estimated to cost in excess of 3400 pounds per year. Healthcare medical management costs were estimated; varying by treatment strategy, they ranged from 250 pounds to 930 pounds per year in patients not experiencing complications. Other longer term costs may also be incurred. Lack of data meant that cost-effectiveness modelling was not feasible.
The clinical effectiveness literature on treatments for idiopathic SRNS in children is very limited. The available evidence suggests a beneficial effect of ciclosporin on remission rates and of cyclophosphamide on time to remission; however, the strength of the conclusions drawn is limited by the poor quality of the included studies. The other treatments included in this review were each evaluated by only one study, and none found a statistically significant effect. There is insufficient evidence to determine whether or not there is a clinically significant difference. The available data on costs and outcomes are sparse and do not permit the reliable modelling of the cost-effectiveness of treatments for SRNS at present. A modelling framework is suggested, should more relevant data become available. A well-designed adequately powered randomised controlled trial comparing ciclosporin with other treatments in children with SRNS without genetic mutation is required.
评估特发性类固醇抵抗性肾病综合征（SRNS）患儿治疗的临床疗效和成本效益。
自建库至2006年2月的电子数据库、研究的参考文献以及该领域的专家。
采用事先商定的公认方法选择研究、评估质量并提取数据。在适当情况下使用随机效应模型进行荟萃分析。在数据允许的情况下，根据肾脏组织病理学进行亚组分析。
临床疗效综述纳入了两项系统评价和11项试验；然而，纳入研究的报告质量和方法通常较差。未发现经济评估。对于所有儿童或局灶节段性肾小球硬化（FSGS）患儿，环磷酰胺加泼尼松与单独使用泼尼松的缓解率无统计学显著差异，环磷酰胺的反应时间在统计学上显著更短（38.4天对95.5天）。静脉注射环磷酰胺与口服环磷酰胺的缓解率无统计学显著差异。静脉注射环磷酰胺时呕吐常见，而口服组出现肺炎和脱发。与安慰剂或支持治疗相比，环孢素在统计学上显著增加了完全缓解患儿的数量，但FSGS亚组除外，两组间感染和高血压等不良反应差异不大。硫唑嘌呤与安慰剂之间未发现差异，每组约13%的患儿出现缓解。18个月甲泼尼龙方案的7例患者中有6例、6个月方案的5例患者中有3例出现完全或部分缓解，两组的肾功能均有改善，且出现高血压和频繁感染等不良事件。静脉注射地塞米松和甲泼尼龙的完全缓解率、部分缓解率、中位反应时间（约10天）和不良事件总数相似，高血压最为常见。高剂量但非低剂量依那普利使6小时尿白蛋白和尿白蛋白与肌酐比值在统计学上显著降低。与安慰剂相比，金枪鱼鱼油在蛋白尿、肌酐清除率、血清肌酐或血脂谱方面未显示出任何统计学显著改善。关于儿童SRNS相关成本的文献非常有限。治疗的药物成本差异很大：8周疗程的环磷酰胺成本不到6英镑，而环孢素疗程每年成本近900英镑。使用他克莫司（环孢素的替代药物）治疗估计每年成本超过3400英镑。估计了医疗保健管理成本；因治疗策略而异，未发生并发症的患者每年为250英镑至930英镑。可能还会产生其他长期成本。缺乏数据意味着成本效益建模不可行。
关于儿童特发性SRNS治疗的临床疗效文献非常有限。现有证据表明环孢素对缓解率有有益作用，环磷酰胺对缓解时间有有益作用；然而，所得结论的力度受到纳入研究质量差的限制。本综述中纳入的其他治疗方法每项仅通过一项研究进行评估，均未发现统计学显著效果。没有足够的证据来确定是否存在临床显著差异。关于成本和结果的现有数据稀少，目前无法对SRNS治疗的成本效益进行可靠建模。建议了一个建模框架，前提是有更多相关数据可用。需要进行一项设计良好、样本量充足的随机对照试验，比较环孢素与无基因突变的SRNS患儿的其他治疗方法。
