Department of Internal Medicine V, Ludwig-Maximilians-University of Munich (LMU), Munich, Germany; Comprehensive Pneumology Center (CPC-M), Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
Department of Pneumology, Hanover Medical School, Member of the German Center for Lung Research (DZL), Hanover, Germany.
J Allergy Clin Immunol Pract. 2021 Mar;9(3):1177-1185.e4. doi: 10.1016/j.jaip.2020.09.014. Epub 2020 Sep 24.
Biological treatments directed against IgE and IL-5 have largely improved outcomes for patients with severe type 2-high asthma. However, a fraction of patients with severe asthma show insufficient treatment outcome under anti-IgE and anti-IL-5/IL-5 receptor α antibodies.
To evaluate whether switching to dupilumab was of benefit in patients with insufficient outcome under previous anti-IgE or anti-IL-5/IL-5 receptor α therapy.
We retrospectively analyzed 38 patients who were switched to dupilumab from a previous anti-IgE or anti-IL-5/IL-5 receptor α medication because of insufficient outcome. We defined response criteria after 3 to 6 months as an improvement in at least 1 of the following criteria without deterioration in the other criteria, comparing values under dupilumab with values under previous antibody therapy: (1) increase of 3 or more in Asthma Control Test score, (2) 50% or more reduction in oral corticosteroid dose, and (3) FEV improvement greater than or equal to 150 mL, and classified patients as responders and nonresponders.
Switch to dupilumab led to a response in 76% of patients. In the total cohort, Asthma Control Test score increased by a mean of 2.9 (P < .0001), whereas exacerbations decreased significantly (P < .0001) and number of oral corticosteroid-dependent patients decreased from 15 to 12. Mean FEV improved by 305 mL (P < .0001). Median fractional exhaled nitric oxide decreased by -30 ppb (P < .0001), whereas eosinophil counts increased by 0.17 G/L (P < .01). There were no significant differences in clinical characteristics between responders and nonresponders to dupilumab. However, patients with increased fractional exhaled nitric oxide (≥25 ppb) during previous antibody therapy were more often responders than patients with low fractional exhaled nitric oxide (<25 ppb) (P < .05).
Altogether, we show that a switch to dupilumab in patients with insufficient outcome under previous biological therapy was effective in most patients.
针对 IgE 和 IL-5 的生物疗法在很大程度上改善了 2 型高重症哮喘患者的预后。然而，仍有一部分重症哮喘患者在接受抗 IgE 和抗 IL-5/IL-5 受体 α 抗体治疗后，疗效仍不充分。
评估在先前抗 IgE 或抗 IL-5/IL-5 受体 α 治疗疗效不充分的患者中，转换使用度普利尤单抗是否有益。
我们回顾性分析了 38 例因疗效不充分而从先前的抗 IgE 或抗 IL-5/IL-5 受体 α 药物转换为度普利尤单抗的患者。我们将治疗后 3 至 6 个月的反应标准定义为以下至少 1 项标准改善而其他标准无恶化，同时将度普利尤单抗治疗下的值与先前抗体治疗下的值进行比较：（1）哮喘控制测试评分增加 3 分或以上，（2）口服皮质类固醇剂量减少 50%或以上，以及（3）FEV1 改善大于或等于 150ml，并将患者分为有反应者和无反应者。
转换使用度普利尤单抗使 76%的患者有反应。在总队列中，哮喘控制测试评分平均增加 2.9（P <.0001），而哮喘加重显著减少（P <.0001），需要口服皮质类固醇的患者数量从 15 例减少到 12 例。平均 FEV1 增加 305ml（P <.0001）。中位呼出气一氧化氮分数降低 30ppb（P <.0001），而嗜酸性粒细胞计数增加 0.17G/L（P <.01）。在对度普利尤单抗有反应和无反应的患者之间，临床特征没有显著差异。然而，在先前的抗体治疗中呼出气一氧化氮分数增加（≥25ppb）的患者比呼出气一氧化氮分数较低（<25ppb）的患者更有可能有反应（P <.05）。
总的来说，我们表明，在先前生物治疗疗效不充分的患者中转换使用度普利尤单抗，大多数患者是有效的。
