Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Center for Rhinology and Allergology Wiesbaden, Wiesbaden, Germany.
Allergy. 2018 Sep;73(9):1775-1783. doi: 10.1111/all.13429. Epub 2018 Apr 16.
Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested-primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations, and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for (clinical) responders in AIT trials; (ii) use of well-documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo-sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organizing two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e-health and m-health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural, and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies, and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments.
变应原免疫疗法（AIT）是治疗变应性鼻炎和变应性哮喘的安全、有效的方法。然而，AIT 的临床疗效仍存在争议，主要是由于临床试验设计、研究人群、治疗制剂和疗效标准的异质性。在讨论了当前的概念和未满足的需求后，一个国际专家小组提出了以下建议：（i）探索和验证 AIT 试验中（临床）应答者的定义；（ii）在将具有相关疾病的受试者纳入 AIT 试验之前，使用有充分记录的标准化激发试验；（iii）在延长的 AIT 试验中监测新致敏和新过敏的发生，并排除多敏参与者；（iv）验证过敏原暴露室相对于自然暴露的有效性；（v）在季节性过敏研究中，关注高峰暴露，但也要考虑组织两个平行的、地理位置不同但其他方面相同的试验；（vi）与监管机构讨论适应性试验设计；（vii）使用电子和移动健康技术来获取更多关于个体过敏原暴露的信息；（viii）启动对潜在的心理、生化、免疫、神经甚至基因组的安慰剂反应标记物的研究；（ix）确定将使过敏儿童更容易、更快地获得 AIT 制剂的试验设计和主要终点；（x）推广和应用报告全身和局部不良事件的标准化方法。最新的技术和试验设计可能为减少 AIT 临床试验中的偏倚和异质性提供新的、合乎伦理的方法。医生、患者组织、公司和监管机构有机会改善 AIT 的临床试验，并最终为患者提供更好的治疗方法。
