Data_Sheet_1_Cetirizine for the treatment of allergic diseases in children: A systematic review and meta-analysis.pdf

ObjectiveThe global prevalence of allergic diseases has led to a negative and extensive impact on the health and lives of a large population of children. This study investigates the efficacy, acceptability, and safety of cetirizine (CTZ) for treating allergic diseases in children and provides evidence-based assertions for decision-making.
MethodsPubMed, Embase, the Cochrane Library, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and the European Union Clinical Trials Register were systematically searched from inception to April 21, 2022. Randomized controlled trials (RCTs) or quasi-RCTs of children with allergic diseases receiving CTZ compared with those receiving placebo or other drugs were included without language limitations. Two investigators independently identified articles, extracted data, conducted meta-analyses, assessed the Cochrane risk of bias of individual studies, and evaluated the evidence certainty using the Grading of Recommendations Assessment, Development, and Evaluation approach; any discrepancies were resolved by consulting with a third investigator. Primary outcomes included scales that evaluated the recovery of allergic conditions in AR, such as the total symptom score (TSS). Secondary outcomes included laboratory test changes, safety (adverse events, AEs), and quality of life (QOL). Data were pooled using the Cochrane Review Manager 5.4, and a fixed-effects model was used if heterogeneity was evaluated as low (I2 < 50%); otherwise, a random-effects model was adopted.
ResultsA total of 22 studies (5,867 patients) were ultimately included [eight with perennial AR, six with seasonal AR, four with atopic dermatitis (AD), and four with other allergic diseases], most of which had a low or unclear risk of bias. Moderate certainty evidence showed that CTZ was found to benefit allergic symptom control [mean difference (MD) of TSS at 1 week: MD, –0.32 (–0.52, –0.12); at 2 weeks: MD, –0.25 (–0.35, –0.14); at 4 weeks: MD, –4.07 (–4.71, –3.43); at 8 weeks: MD, –4.22 (–4.73, –3.72); at 12 weeks: MD, –5.63 (–6.14, –5.13); all P-values were less than 0.05] and QOL [at 12 weeks: MD, –23.16 (–26.92, –19.39); P < 0.00001] in children with AR. It had similar efficacy compared with other antihistamines (AHs) or montelukast, without showing better control of AD severity in children. Moderate-to-low certainty evidence demonstrated that CTZ was well tolerated and did not increase the risk of severe and overall AEs, cardiotoxicity, damage to the central nervous and digestive systems, or other systems in children, except for the risk of somnolence [risk ratio, 1.62 (1.02, 2.57); P = 0.04, compared with placebo].
ConclusionModerate-to-low certainty evidence revealed that CTZ could improve clinical improvement and QOL in children with AR and have comparable efficacy with other AHs. CTZ is well tolerated in the pediatric population, except for an increased risk of somnolence.
Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021262767].

### 研究目的（Objective）
全球过敏性疾病的患病率持续攀升，对大量儿童群体的健康与生活造成了消极且广泛的影响。本研究旨在评估西替利嗪（cetirizine, CTZ）治疗儿童过敏性疾病的有效性、可接受性与安全性，为临床决策提供循证依据。

### 研究方法（Methods）
本研究系统检索了PubMed、Embase、Cochrane图书馆、世界卫生组织国际临床试验注册平台、美国临床试验数据库（ClinicalTrials.gov）及欧盟临床试验登记册，检索时限为各数据库建库至2022年4月21日。纳入对比西替利嗪与安慰剂或其他药物治疗儿童过敏性疾病的随机对照试验（RCT）或类随机对照试验（quasi-RCT），无语言限制。由两名研究者独立完成文献筛选、数据提取、Meta分析、单项研究的Cochrane偏倚风险评估，并采用推荐等级评估、制定与评价（Grading of Recommendations Assessment, Development and Evaluation, GRADE）方法评价证据确定性；若存在分歧，则咨询第三名研究者以达成共识。主要结局指标包括评估变应性鼻炎（AR）患儿过敏状态恢复情况的量表，如总症状评分（total symptom score, TSS）；次要结局指标包括实验室检测指标变化、安全性（不良事件, AEs）及生活质量（quality of life, QOL）。采用Cochrane系统评价管理器5.4版进行数据合并，若异质性评估为低（I²<50%）则使用固定效应模型，反之则采用随机效应模型。

### 研究结果（Results）
最终纳入22项研究，共计5867例患者[其中常年性变应性鼻炎8项、季节性变应性鼻炎6项、特应性皮炎（atopic dermatitis, AD）4项、其他过敏性疾病4项]，多数研究的偏倚风险为低或不确定。中等确定性证据显示，西替利嗪可改善变应性鼻炎患儿的过敏症状控制：1周时总症状评分均数差（MD）为-0.32（95%CI：-0.52~-0.12）；2周时MD=-0.25（95%CI：-0.35~-0.14）；4周时MD=-4.07（95%CI：-4.71~-3.43）；8周时MD=-4.22（95%CI：-4.73~-3.72）；12周时MD=-5.63（95%CI：-6.14~-5.13），所有P值均<0.05；同时可改善患儿生活质量（12周时MD=-23.16，95%CI：-26.92~-19.39；P<0.00001）。西替利嗪与其他抗组胺药（antihistamines, AHs）或孟鲁司特的疗效相当，但未展现出对儿童特应性皮炎严重程度的更佳控制效果。中低确定性证据表明，西替利嗪耐受性良好，除嗜睡风险外[风险比（RR）=1.62，95%CI：1.02~2.57；P=0.04，与安慰剂组比较]，未增加严重不良事件、总体不良事件、心脏毒性、中枢神经系统与消化系统损伤或其他系统不良反应的发生风险。

### 研究结论（Conclusion）
中低确定性证据显示，西替利嗪可改善变应性鼻炎患儿的临床结局与生活质量，且与其他抗组胺药疗效相当。西替利嗪在儿科人群中耐受性良好，仅嗜睡风险有所升高。

### 系统评价注册信息
本系统评价注册于[https://www.crd.york.ac.uk/PROSPERO/]，注册标识符为[CRD42021262767]。