Clinical Outcomes of Tralokinumab and Lebrikizumab in Japanese Atopic Dermatitis Patients With Persistent Head and Neck Dermatitis After Long‐Term Treatment With Dupilumab: A Single‐Center Retrospective Study

Dupilumab, an anti-interleukin (IL)-4Rα antibody, has shown efficacy for moderate-to-severe atopic dermatitis (AD). However, some patients experience persistent lesions on the head and neck despite improvements on the limbs and trunk after long-term treatment with dupilumab [1, 2]. Although some patients switch to tralokinumab or lebrikizumab (anti-IL-13 antibodies) in such cases, evidence demonstrating the effectiveness of these treatments is limited. To our knowledge, this article is the first to report the clinical outcomes of lebrikizumab in AD patients with persistent head and neck dermatitis after long-term dupilumab treatment. We retrospectively investigated the clinical outcomes of anti-IL-13 antibodies in patients who switched due to persistent head and neck dermatitis after more than 1 year of dupilumab therapy. All AD patients at our department meeting these criteria and who had switched to tralokinumab or lebrikizumab by December 2024 were included. The total Eczema Area and Severity Index (EASI) and head and neck EASI 3 months after switching were evaluated. Data were collected from medical records, excluding patients with insufficient data. Assessments were performed by trained dermatologists. This study was approved by the Teikyo University Institutional Review Board (24-050) and conducted according to the Declaration of Helsinki. Informed consent was obtained via opt-out on our website. Twelve patients (female, 1; male, 11) were analyzed. Median age was 43.5 years (1st quartile, 33.25; 3rd quartile, 50). All switched directly from dupilumab to tralokinumab or lebrikizumab. As shown in Table 1, all but one patient showed a decrease in head and neck EASI, with a significant reduction from 0.9 (0.55, 1.65) to 0.3 (0.175, 0.9) overall (p = 0.0088) and from 1.5 (0.9, 2.1) to 0.4 (0.2, 0.9) in the lebrikizumab group (p = 0.0224). A numerical decrease from 0.8 (0.5, 1.05) to 0.2 (0.15, 0.8) was observed in the tralokinumab group (p = 0.1563). Previous reports include Schlösser et al., who found improvement in 80% of patients in the Netherlands switching to tralokinumab [3], and Beyrouti et al., who reported 33.3% improvement in French patients with dupilumab-induced facial redness [4]. Differences may reflect variations in evaluation methods and/or ethnicity. Regarding switching to lebrikizumab, no data have been previously reported, making our findings novel. Previous reports have suggested that excessive suppression of Th2-mediated pathways by dupilumab might paradoxically induce head and neck dermatitis. Levine et al. [5] described cases of cicatrizing blepharoconjunctivitis improving after dupilumab dose reduction, supporting this hypothesis. In contrast, tralokinumab and lebrikizumab selectively inhibit IL-13, providing a relatively weaker blockade of Th2 immunity compared with dupilumab. This differential immunomodulation may explain why patients with persistent head and neck dermatitis during dupilumab treatment can show improvement after switching to IL-13 inhibitors. Our study has several limitations, including the retrospective design, small sample size, and male predominance of the cohort, which may limit generalizability. In conclusion, switching to tralokinumab or lebrikizumab could be considered for AD patients with persistent head and neck lesions during dupilumab treatment. Our study provides the first evidence supporting the favorable clinical outcomes of lebrikizumab in this context, expanding therapeutic options for this challenging subset of patients. M.K. received honoraria from LEO Pharma and Eli Lilly for lectures. Y.T. received honoraria from LEO Pharma and Eli Lilly for lectures and grants unrelated to this study. Yayoi Tada is an editorial board member of the Journal of Dermatology and a coauthor of this article. To minimize bias, she was excluded from all editorial decision making related to the acceptance of this article for publication. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.