Sato Emi, Obonai Naoko, Iwata Mayuko, Ito Kotaro, Imafuku Shinichi
Department of Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Department of Dermatology, Ito Dermatology Clinic, Kitsuki, Oita, Japan.
Front Immunol. 2025 Aug 11;16:1639932. doi: 10.3389/fimmu.2025.1639932. eCollection 2025.
Molecular targeted therapies, including advanced atopic dermatitis (AD) treatment with Janus kinase 1 inhibitors (JAK1i) and anti-interleukin-13 antibodies (IL-13Ab), are emerging as effective options. However, the predictive biomarkers for treatment responses remain unclear. Therefore, this study compared the short-term efficacy of JAK1i and IL-13Ab and explored relevant biomarkers.
This retrospective analysis was conducted in 75 patients with moderate-to-severe AD treated at Fukuoka University Hospital. Relevant biomarkers, including eosinophil count and thymus and activation-regulated chemokine (TARC) levels, were measured at baseline and 3 months. Eczema Area and Severity Index (EASI) and Peak Pruritus Numerical Rating Scale (PP-NRS) scores were also assessed.
Patients received JAK1i (n=37; abrocitinib, n=16; upadacitinib, n=21) or IL-13Ab (n=38; lebrikizumab, n=21; tralokinumab, n=17). At 3 months, no significant difference was observed between JAK1i and IL-13Ab in achieving EASI 75 (odds ratio [OR] = 0.83, p=0.76) or in the incidence of adverse events (OR = 1.40, p=0.55). However, JAK1i was associated with higher odds of achieving PP-NRS 4 (OR=9.36, p=0.0063) and PP-NRS 0/1 (OR=34.61, p<0.0001). In the JAK1i group, eosinophil count reduction correlated with EASI improvement (univariate: R=0.525, p=0.0009; adjusted: β = 0.567, p=0.0004). In the IL-13Ab group, TARC reduction correlated with EASI improvement (univariate: R=0.677, p<0.0001; adjusted: β = 0.661, p<0.0001).
JAK1i showed greater antipruritic effects than IL-13Ab at 3 months, likely due to interleukin (IL)-31 inhibition. Eosinophil count reduction was the most reflective biomarker of JAK1i efficacy, potentially due to IL-5 suppression, whereas TARC improvement was significantly associated with patients' treatment response to IL-13Ab. These findings highlight the need for further long-term studies.
分子靶向疗法，包括使用 Janus 激酶 1 抑制剂（JAK1i）和抗白细胞介素-13 抗体（IL-13Ab）治疗重度特应性皮炎（AD），正逐渐成为有效的治疗选择。然而，治疗反应的预测生物标志物仍不明确。因此，本研究比较了 JAK1i 和 IL-13Ab 的短期疗效，并探索了相关生物标志物。
本回顾性分析纳入了 75 例在福冈大学医院接受治疗的中重度 AD 患者。在基线和 3 个月时测量了包括嗜酸性粒细胞计数和胸腺与活化调节趋化因子（TARC）水平在内的相关生物标志物。还评估了湿疹面积和严重程度指数（EASI）以及瘙痒峰值数字评定量表（PP-NRS）评分。
患者接受 JAK1i（n = 37；阿布昔替尼，n = 16；乌帕替尼，n = 21）或 IL-13Ab（n = 38；乐必妥珠单抗，n = 21；曲罗芦单抗，n = 17）治疗。在 3 个月时，JAK1i 和 IL-13Ab 在达到 EASI 改善 75%（优势比[OR] = 0.83，p = 0.76）或不良事件发生率（OR = 1.40，p = 0.55）方面没有显著差异。然而，JAK1i 在达到 PP-NRS 为 4（OR = 9.36，p = 0.0063）和 PP-NRS 为 0/1（OR = 34.61，p < 0.0001）方面的优势更高。在 JAK1i 组中，嗜酸性粒细胞计数的降低与 EASI 的改善相关（单变量：R = 0.525，p = 0.0009；校正后：β = 0.567，p = 0.0004）。在 IL-13Ab 组中，TARC 的降低与 EASI 的改善相关（单变量：R = 0.677，p < 0.0001；校正后：β = 0.661，p < 0.0001）。
JAK1i 在 3 个月时显示出比 IL-13Ab 更强的止痒作用，可能是由于对白介素（IL）-31 的抑制。嗜酸性粒细胞计数的降低是 JAK1i 疗效最具代表性的生物标志物，可能是由于对 IL-5 的抑制，而 TARC 的改善与患者对 IL-13Ab 的治疗反应显著相关。这些发现突出了进一步进行长期研究的必要性。
