Brozek Jan L, Firmino Ramon T, Bognanni Antonio, Arasi Stefania, Ansotegui Ignacio, Assa'ad Amal H, Bahna Sami L, Canani Roberto Berni, Bozzola Martin, Chu Derek K, Dahdah Lamia, Dupont Christophe, Dziechciarz Piotr, Ebisawa Motohiro, Galli Elena, Horvath Andrea, Kamenwa Rose, Lack Gideon, Li Haiqi, Martelli Alberto, Nowak-Węgrzyn Anna, Papadopoulos Nikolaos G, Pawankar Ruby, Roldan Yetiani, Said Maria, Sánchez-Borges Mario, Shamir Raanan, Spergel Jonathan M, Szajewska Hania, Terracciano Luigi, Vandenplas Yvan, Venter Carina, Waffenschmidt Siw, Waserman Susan, Warner Amena, Wong Gary W K, Fiocchi Alessandro, Schünemann Holger J
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada.
Department of Medicine, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada.
World Allergy Organ J. 2022 Apr 23;15(4):100646. doi: 10.1016/j.waojou.2022.100646. eCollection 2022 Apr.
The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects.
These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA.
WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment.
After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled "conditional" due to the low certainty about the health effects based on the available evidence.
Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.
牛奶过敏（CMA）在婴儿中的患病率约为2%-4.5%，在成人中低于0.5%。大多数儿童在幼儿期会摆脱牛奶过敏，尤其是对烘焙奶制品的过敏。对于尚未摆脱CMA的患者，已将未加热牛奶的免疫疗法作为一种治疗选择，但必须在益处与不良反应之间进行权衡。
世界过敏组织（WAO）的这些循证指南旨在支持患者、临床医生及其他人员在决定使用口服和经皮免疫疗法治疗IgE介导的CMA时做出决策。
WAO组建了一个多学科指南小组，成员构成均衡，纳入了所有利益相关者的观点，以尽量减少利益冲突带来的潜在偏差。麦克马斯特大学GRADE中心支持指南制定过程，包括更新或进行系统的证据审查。该小组根据临床问题和结果对临床医生及患者的重要性进行优先排序。采用了推荐分级评估、制定与评价（GRADE）方法，包括GRADE证据到决策框架，并征求了公众意见。
在仔细审查总结的证据并进行深入讨论后，WAO指南小组建议：a）对于确诊为IgE介导的CMA且更看重能够食用定量牛奶而非避免治疗带来的严重不良反应的个体，使用未加热牛奶进行口服免疫疗法；b）对于更看重避免治疗带来的严重不良反应而非能够食用定量牛奶的个体，不使用未加热牛奶进行口服免疫疗法；c）对于开始使用未加热牛奶进行口服免疫疗法的个体，使用奥马珠单抗；d）对于不耐受未加热和烘焙牛奶的个体，不使用烘焙牛奶进行口服免疫疗法；e）在研究环境之外不使用经皮免疫疗法。由于基于现有证据对健康影响的确定性较低，这些建议被标记为“有条件的”。
临床医生、患者及其家属在决定治疗方案之前，可能需要讨论口服免疫疗法治疗IgE介导的CMA的所有潜在利弊，并将其与患者的价值观和偏好相结合。需要进行更有力的研究，以更确定地确定哪些干预措施可能最有益且危害最小，并开发更安全、低成本且公平的治疗方法。
