Faculty of Medicine, Al-Azhar University, Damietta, Egypt.
Faculty of Pharmacy, Kafr El sheik university, Kafr El Sheik, Egypt.
BMC Pediatr. 2024 Mar 23;24(1):206. doi: 10.1186/s12887-024-04526-3.
Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions.
To evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients.
We identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion. Two independent reviewers evaluated the identified studies' titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome, we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3.
Among the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200 mg dosage (overall mean difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200 mg dosage (overall mean difference: -0.34, p < 0.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200 mg), vomiting (200 mg), and irritability (200 mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite.
Trofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200 mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.
雷特综合征是一种罕见的遗传性神经发育障碍，主要影响女性。其表现为获得性技能丧失、沟通障碍和刻板手运动。鉴于雷特综合征的治疗选择有限，因此迫切需要有效的干预措施。
评估替诺福肽在报告雷特综合征患者的随机对照试验（RCT）中的安全性和疗效。
我们从四个数据库（Scopus、PubMed、Web of Science 和 Cochrane CENTRAL）中确定了 109 篇文章。在去除重复项后，我们将其缩小到 59 篇文章进行进一步评估。我们纳入了评估替诺福肽在雷特综合征患者中的疗效和安全性的 RCT。有三项研究符合纳入标准。两名独立的审查员评估了已确定研究的标题、摘要和全文，提取了相关数据。我们使用 Cochrane 风险偏倚（RoB）2.0 工具评估了研究的质量。然后，我们根据异质性的显著性，使用固定效应模型进行荟萃分析；否则，我们使用随机效应模型。基于结果的性质，我们分析了平均差异或优势比。使用 RevMan 版本 5.3 进行分析。
在替诺福肽组的 181 名患者和安慰剂组的 134 名患者的分析结果中，在 200mg 剂量下观察到雷特综合征行为问卷（RSBQ）评分显著改善（总体平均差异：-3.53，p=0.001）。在 200mg 剂量下，临床总体印象改善（CGI-I）评分显著改善（总体平均差异：-0.34，p<0.0001）。在运动行为评估（MBA）或前 3 名护理人员关注的问题方面没有观察到实质性变化。我们评估了不同剂量的治疗中出现的不良事件（TEAEs），并注意到腹泻（200mg）、呕吐（200mg）和易怒（200mg）与替诺福肽显著相关。然而，我们没有发现任何剂量与食欲减退发生率之间存在显著关联。
替诺福肽在 200mg 剂量下显示出改善 RSBQ 和 CGI-I 评分的潜力。尽管在 MBA 和前 3 名护理人员关注的问题方面没有发现实质性变化。不良事件与特定剂量相关。
