Supplementary Material for: Title: Efficacy and safety of oral immunotherapy for Peanut Allergy A Grade assessed systematic review and meta analysis of randomised controlled trials

Introduction :
Peanut allergy is a common and potentially life-threatening condition affecting up to 2% of children in Western countries. Management traditionally relied on avoidance, but in 2020, the FDA approved peanut oral immunotherapy (pOIT) to induce desensitization. This meta-analysis evaluates the efficacy and safety of pOIT versus placebo by incorporating newly published trials to inform clinical decision-making.

Methods:
This systematic review and meta-analysis followed PRISMA guidelines and Cochrane methodology, with registration number . Randomized controlled trials comparing peanut oral immunotherapy (pOIT) to placebo in IgE-mediated peanut allergy were included. Primary outcomes were gastrointestinal disorders and wheezing. Data were pooled using a random-effects model in RevMan 5.4.1, and evidence certainty was assessed using the GRADE approach.

Results :
This meta-analysis included 15 RCTs with 1530 patients (1014 pOIT, 516 placebo). pOIT significantly increased gastrointestinal disorders (RR = 1.90; 95% CI: 1.25–2.89; p = 0.003) and epinephrine use (RR = 2.29; 95% CI: 1.43–3.67; p = 0.0006). No significant differences were observed in wheezing, eczema, respiratory disorders, respiratory symptoms, or vomiting. Heterogeneity ranged from low to high across outcomes. Certainty of evidence was rated high for gastrointestinal disorders, epinephrine use, and respiratory symptoms; moderate for wheezing, eczema, and vomiting. Heterogeneity was primarily driven by specific outlier studies, as identified through sensitivity analyses.

Conclusion :
Peanut oral immunotherapy (pOIT) increases desensitization in patients with peanut allergy but is associated with a significantly higher risk of gastrointestinal side effects and epinephrine use, reflecting an increased rate of systemic allergic reactions. While outcomes such as wheezing, eczema, and respiratory symptoms showed no significant differences, variability in study design and adverse event reporting limits broad generalizability. These findings emphasize the need for careful patient selection, pre-treatment counseling, and close monitoring. Future research should focus on protocol standardization, long-term outcomes, and strategies to minimize adverse effects while maintaining efficacy

引言：
花生过敏是一种常见且可能危及生命的疾病，在西方国家中影响多达2%的儿童。传统管理方案以回避疗法为主，但2020年美国食品药品监督管理局（FDA）批准了花生口服免疫治疗（peanut oral immunotherapy, pOIT）以诱导脱敏。本荟萃分析（meta-analysis）纳入最新发表的临床试验，对比花生口服免疫治疗（pOIT）与安慰剂的疗效与安全性，旨在为临床决策提供参考。

方法：
本系统综述（systematic review）与荟萃分析遵循PRISMA指南及Cochrane协作网方法学，注册编号未提及。纳入对比IgE介导型花生过敏患者接受花生口服免疫治疗（pOIT）与安慰剂的随机对照试验（randomized controlled trial, RCT）。主要结局指标为胃肠道不良反应与喘息。采用RevMan 5.4.1软件的随机效应模型（random-effects model）合并数据，并使用GRADE分级方法评估证据确定性。

结果：
本荟萃分析共纳入15项随机对照试验，涉及1530例患者（1014例接受pOIT治疗，516例接受安慰剂治疗）。pOIT可显著升高胃肠道不良反应发生风险（相对风险（relative risk, RR）=1.90；95%置信区间（95% confidence interval, 95% CI）：1.25~2.89；p=0.003）及肾上腺素使用需求（RR=2.29；95%CI：1.43~3.67；p=0.0006）。在喘息、湿疹、呼吸系统疾病、呼吸道症状及呕吐方面未观察到显著差异。不同结局指标的异质性（heterogeneity）程度从低至高不等。胃肠道不良反应、肾上腺素使用及呼吸道症状的证据确定性被评为高级；喘息、湿疹及呕吐的证据确定性为中级。敏感性分析（sensitivity analyses）显示，异质性主要由特定的异常值研究导致。

结论：
花生口服免疫治疗（pOIT）可提升花生过敏患者的脱敏效果，但会显著增加胃肠道不良反应及肾上腺素使用风险，反映出全身性过敏反应发生率升高。尽管喘息、湿疹及呼吸道症状等结局无显著差异，但研究设计与不良事件报告的异质性限制了研究结果的广泛外推性。本研究结果强调，需严格筛选患者、开展治疗前咨询并进行密切监测。未来研究应聚焦于方案标准化、长期结局评估，以及在维持疗效的同时降低不良反应的策略。