Lamothe Pedro A, Pruett Charles Lewis Humphrey, Smirnova Natalia, Shepherd Aaron, Runnstrom Martin C, Park Jiwon, Zhang Rebecca H, Zhao Leshan, Swenson Colin, Lee F Eun-Hyung
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Emory University School of Medicine, Atlanta, Ga.
J Allergy Clin Immunol Glob. 2024 Nov 12;4(1):100369. doi: 10.1016/j.jacig.2024.100369. eCollection 2025 Feb.
Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to . Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.
We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.
We performed a retrospective analysis of patients with ABPA treated with asthma biologics, and measured outcomes of respiratory exacerbations, daily oral corticosteroids, and antifungals. We assessed these variables while individuals were treated with 1 of 3 biologic classes: anti-IgE, anti-IL-5/IL-5 receptor alpha (IL-5Ra), anti-IL-4 receptor alpha (IL-4Ra).
A total of 21 patients were included in our analysis. Anti-IL-4Ra was associated with a significantly lower number of exacerbations and oral corticosteroid use compared with anti-IgE or anti-IL-5/IL-5Ra therapies. Anti-IL-4Ra also had significantly lower antifungal use than anti-IgE, and there was a trend toward lower antifungal use when compared with anti-IL-5/IL-5Ra. In a subgroup of 10 patients treated with 2 or more biologics sequentially, we found that 8 of them achieved clinical control on anti-IL-4Ra therapy after failing anti-IgE and/or anti-IL-5/IL-5Ra therapies.
Dupilumab blocks the IL-4Ra, resulting in the downstream inhibition of both IL-4 and IL-13 effector pathways. Dupilumab may benefit patients with ABPA by inhibiting the generation of airway mucus (IL-13), and by reducing local B-cell differentiation into IgE antibody-secreting cells (IL-4). On the basis of our findings and with the known molecular mechanisms of dupilumab, we believe that anti-IL-4Rα-targeted therapy may be more effective than anti-IgE or anti-IL-5/IL-5Rα therapies to treat ABPA.
变应性支气管肺曲霉病（ABPA）是一种由对曲霉的2型反应过度活跃引起的疾病。初步研究表明，哮喘生物制剂可有效治疗ABPA，但尚不清楚哪种生物制剂类别更具优势。
我们试图比较哮喘生物制剂治疗ABPA的有效性。
我们对接受哮喘生物制剂治疗的ABPA患者进行了回顾性分析，并测量了呼吸道加重、每日口服糖皮质激素和抗真菌药物的治疗结果。在个体接受3种生物制剂类别之一治疗时，我们评估了这些变量：抗IgE、抗白细胞介素-5/白细胞介素-5受体α（IL-5Ra）、抗白细胞介素-4受体α（IL-4Ra）。
我们的分析共纳入了21例患者。与抗IgE或抗IL-5/IL-5Ra疗法相比，抗IL-4Ra与显著更低的加重次数和口服糖皮质激素使用量相关。抗IL-4Ra的抗真菌药物使用量也显著低于抗IgE，与抗IL-5/IL-5Ra相比有抗真菌药物使用量更低的趋势。在10例序贯接受2种或更多种生物制剂治疗的患者亚组中，我们发现其中8例在抗IgE和/或抗IL-5/IL-5Ra治疗失败后，在抗IL-4Ra治疗时实现了临床控制。
度普利尤单抗可阻断IL-4Ra，从而对IL-4和IL-13效应通路产生下游抑制作用。度普利尤单抗可能通过抑制气道黏液生成（IL-13）以及减少局部B细胞分化为分泌IgE抗体的细胞（IL-4），使ABPA患者受益。基于我们的研究结果以及度普利尤单抗已知的分子机制，我们认为抗IL-4Rα靶向治疗在治疗ABPA方面可能比抗IgE或抗IL-5/IL-5Rα治疗更有效。
