Kobayashi Toshiyuki, Sato Hironori, Nagasawa Koo, Hayata Eri, Tanaka Saori, Kurihara Erika, Yamamoto Takeshi, Nakano Taiji, Ozawa Yoshihito, Yamaide Fumiya, Inoue Yuzaburo, Suzuki Shuichi, Arima Takayasu, Tomiita Minako, Hamada Hiromichi, Ishiwada Naruhiko
Department of Paediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Paediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan
BMJ Open. 2025 Aug 3;15(8):e101050. doi: 10.1136/bmjopen-2025-101050.
Atopic dermatitis (AD) is a chronic inflammatory skin condition that impairs the quality of life of affected paediatric patients and their families. Dupilumab, an antagonist of the shared alpha chain subunit of the cytokines interleukin-4 and interleukin-13, has revolutionised the management of moderate-to-severe AD by effectively targeting type 2 inflammation. However, live attenuated vaccines, including live attenuated influenza vaccines (LAIVs), are contraindicated during dupilumab therapy owing to limited safety data. This restriction poses challenges to immunisation strategies, particularly in paediatric populations. This study aims to evaluate the safety and efficacy of LAIV in paediatric patients with AD undergoing dupilumab therapy.
This multicentre, prospective, single-arm, open-label trial will enrol 50 paediatric patients aged 2-18 years with AD undergoing dupilumab treatment. The participants will receive intranasal LAIV, followed by a 25-week observation period after vaccination. The primary outcome is the proportion of participants with a four-fold or greater increase in haemagglutination inhibition titres against influenza strains A(H1N1), A(H3N2) and B at 4 weeks post vaccination. The secondary outcomes include the incidence of influenza and systemic or local adverse events, such as injection site reactions, fever and other influenza-like symptoms observed within 4 weeks of vaccination. Exploratory endpoints include the evaluation of immunosuppressive markers such as neutrophil counts, lymphocyte subsets and serum immunoglobulin G levels. Safety analyses will assess the frequency of each adverse event, whereas efficacy analyses will focus on immunogenicity and influenza incidence during the 25-week follow-up period. This study aims to provide critical safety and immunogenicity data to guide immunisation strategies in biologically treated paediatric patients with AD.
This study complies with the principles of the Declaration of Helsinki and received ethics approval from the Institutional Review Board of Chiba University Hospital as a specified clinical trial. Informed consent and assent will be obtained as appropriate based on the participants' ages. These findings will be disseminated through peer-reviewed journals and scientific conferences to inform clinical vaccination strategies for biologically treated populations.
jRCTs031240442.
特应性皮炎（AD）是一种慢性炎症性皮肤病，会损害患病儿童患者及其家庭的生活质量。度普利尤单抗是细胞因子白细胞介素-4和白细胞介素-13共享α链亚基的拮抗剂，通过有效靶向2型炎症，彻底改变了中重度AD的治疗方式。然而，由于安全性数据有限，在度普利尤单抗治疗期间禁忌接种减毒活疫苗，包括减毒活流感疫苗（LAIV）。这种限制给免疫策略带来了挑战，尤其是在儿科人群中。本研究旨在评估LAIV在接受度普利尤单抗治疗的AD儿科患者中的安全性和有效性。
这项多中心、前瞻性、单臂、开放标签试验将招募50名年龄在2至18岁、正在接受度普利尤单抗治疗的AD儿科患者。参与者将接受鼻内LAIV接种，随后在接种疫苗后进行25周的观察期。主要结局是接种疫苗后4周时，针对甲型（H1N1）、甲型（H3N2）和乙型流感毒株的血凝抑制效价升高四倍或更高的参与者比例。次要结局包括流感发病率以及接种疫苗后4周内观察到的全身或局部不良事件，如注射部位反应、发热和其他流感样症状。探索性终点包括评估免疫抑制标志物，如中性粒细胞计数、淋巴细胞亚群和血清免疫球蛋白G水平。安全性分析将评估每种不良事件的发生频率，而有效性分析将聚焦于25周随访期内的免疫原性和流感发病率。本研究旨在提供关键的安全性和免疫原性数据，以指导生物治疗的AD儿科患者的免疫策略。
本研究遵循《赫尔辛基宣言》的原则，并作为特定临床试验获得了千叶大学医院机构审查委员会的伦理批准。将根据参与者的年龄酌情获得知情同意和同意。这些研究结果将通过同行评审期刊和科学会议进行传播，以为生物治疗人群的临床疫苗接种策略提供参考。
jRCTs031240442。
