Department of Medicine, McMaster University, Hamilton, Ontario, ON, Canada; St Joseph's Healthcare Hamilton, Hamilton, Ontario, ON, Canada.
Division of Allergy & Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lancet. 2019 Jun 1;393(10187):2222-2232. doi: 10.1016/S0140-6736(19)30420-9. Epub 2019 Apr 25.
Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus allergen avoidance or placebo (no oral immunotherapy) for peanut allergy.
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930.
12 trials (n=1041; median age across trials 8·7 years [IQR 5·9-11·2]) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio [RR] 3·12 [95% CI 1·76-5·55], I=0%, risk difference [RD] 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio [IRR] 2·72 [1·57-4·72], I=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 [1·27-3·83], I=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (p=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 [1·00-3·66], I=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 [95%CI 1·35-2·38], I=0%, high-certainty; angioedema: 2·25 [1·13-4·47], I=0%, high-certainty; upper tract respiratory reactions: 1·36 [1·02-1·81], I=0%, moderate-certainty; lower tract respiratory reactions: 1·55 [0·96-2·50], I=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 [95% CI 6·82-22·61], I=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 [0·87-1·69], I=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses.
In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed.
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口服免疫疗法是一种新兴的治疗花生过敏的实验性疗法，但它的益处和危害尚不清楚。我们系统地回顾了口服免疫疗法与过敏原回避或安慰剂（无口服免疫疗法）治疗花生过敏的疗效和安全性。
在花生过敏原免疫治疗，明确证据（PACE）系统评价和荟萃分析中，我们检索了 MEDLINE、EMBASE、Cochrane 对照试验注册库、拉丁美洲和加勒比健康科学文献、中国国家知识基础设施、世界卫生组织临床试验注册平台、美国食品和药物管理局以及欧洲药品管理局数据库，从成立到 2018 年 12 月 6 日，用于比较口服免疫疗法与无口服免疫疗法治疗花生过敏的随机对照试验，无语言限制。我们独立地进行了两次筛选研究、提取数据和评估偏倚风险。主要结局包括过敏反应、过敏或不良反应、肾上腺素使用和生活质量，采用随机效应进行荟萃分析。我们采用 GRADE 方法评估证据的确定性（质量）。这项研究在 PROSPERO 上注册，编号为 CRD42019117930。
12 项试验（n=1041；试验中位数年龄 8.7 岁[IQR 5.9-11.2]）表明，与无口服免疫疗法相比，口服免疫疗法增加了过敏反应的风险（风险比[RR]3.12[95%CI 1.76-5.55]，I=0%，风险差异[RD]15.1%，高度确定性）、过敏反应的频率（发病率比[IRR]2.72[1.57-4.72]，I=0%，RD 12.2%，高度确定性）和肾上腺素的使用（RR 2.21[1.27-3.83]，I=0%，RD 4.5%，高度确定性）在建立和维持期间也相似（p=0.92）。口服免疫疗法增加了严重不良事件（RR 1.92[1.00-3.66]，I=0%，RD 5.7%，中度确定性）和非过敏反应（呕吐：RR 1.79[95%CI 1.35-2.38]，I=0%，高度确定性；血管性水肿：2.25[1.13-4.47]，I=0%，高度确定性；上呼吸道反应：1.36[1.02-1.81]，I=0%，中度确定性；下呼吸道反应：1.55[0.96-2.50]，I=28%，中度确定性）。通过监督性挑战，即预防门诊外反应的替代物，口服免疫疗法更有可能通过（RR 12.42[95%CI 6.82-22.61]，I=0%，RD 36.5%，高度确定性）。两组之间的生活质量没有差异（联合父母和自我报告 RR 1.21[0.87-1.69]，I=0%，RD 0.03%，低确定性）。这些发现对 IRR、试验序贯、亚组和敏感性分析具有稳健性。
在花生过敏患者中，有确凿证据表明，现有的花生口服免疫疗法方案会大大增加过敏和过敏反应，尽管它们有效地诱导了脱敏。需要更安全的花生过敏治疗方法和严格的随机对照试验来评估对患者重要的结局。
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