Soendergaard Marianne Baastrup, Hansen Susanne, Håkansson Kjell Erik Julius, von Bülow Anna, Bjerrum Anne-Sofie, Schmid Johannes Martin, Johansson Sofie Lock, Rasmussen Linda Makowska, Johnsen Claus Rikard, Bertelsen Barbara Bonnesen, Krogh Niels Steen, Hilberg Ole, Ulrik Charlotte Suppli, Porsbjerg Celeste
Department of Respiratory Medicine, Copenhagen University Hospital-Bispebjerg, Copenhagen, Denmark.
Centre for Clinical Research and Prevention, Frederiksberg Hospital, Copenhagen, Denmark.
Allergy. 2025 Apr;80(4):986-995. doi: 10.1111/all.16425. Epub 2024 Dec 14.
In patients with severe asthma, treatment with anti-interleukin-5 (IL-5) biologics can lead to a reduction in fractional exhaled nitric oxide (FeNO) in some patients. The clinical implications of varying FeNO responses to anti-IL-5 biologics remain unclear. This study aims to categorise patients based on their FeNO response to anti-IL-5 biologics and evaluate the association of these categories with clinical outcomes.
We used the Danish Severe Asthma Register (DSAR) to identify the early FeNO response profiles in patients receiving anti-IL5 biologics. We defined FeNO responders as patients with elevated FeNO levels at baseline and a decrease corresponding to the minimal clinically important difference (MCID) at 4 months of follow-up and FeNO non-responders as those who did not experience a decrease.
We identified 403 patients on anti-IL5 treatment in DSAR, and 265 (66%) had elevated FeNO levels at baseline. After 4 months of treatment, 151 (57%) patients showed a significant decrease in FeNO levels, and 114 (43%) did not. FeNO responders were more likely to achieve clinical remission of asthma (34% vs. 19%, p = 0.01, OR 2.11, CI 1.04, 5.18, p = 0.03) than FeNO non-responders after 12 months of treatment. The higher remission rates in FeNO responders mainly reflected a higher rate of normalisation of lung function.
FeNO levels were reduced after anti-IL5 treatment in a significant proportion of patients treated with anti-IL5, and this was associated with clinical remission. Early FeNO response to anti-IL5 could potentially be used as a biomarker to guide management decisions with biologics towards remission of disease in severe asthma.
在重度哮喘患者中，使用抗白细胞介素-5（IL-5）生物制剂治疗可使部分患者的呼出一氧化氮分数（FeNO）降低。FeNO对抗IL-5生物制剂的不同反应的临床意义仍不明确。本研究旨在根据患者对抗IL-5生物制剂的FeNO反应进行分类，并评估这些类别与临床结局的关联。
我们使用丹麦重度哮喘登记册（DSAR）来确定接受抗IL-5生物制剂治疗患者的早期FeNO反应特征。我们将FeNO反应者定义为基线时FeNO水平升高且在随访4个月时下降至最小临床重要差异（MCID）的患者，将FeNO无反应者定义为未出现下降的患者。
我们在DSAR中确定了403例接受抗IL-5治疗的患者，其中265例（66%）基线时FeNO水平升高。治疗4个月后，151例（57%）患者的FeNO水平显著下降，114例（43%）未下降。治疗12个月后，FeNO反应者比FeNO无反应者更有可能实现哮喘临床缓解（34%对19%，p = 0.01，OR 2.11，CI 1.04，5.18，p = 0.03）。FeNO反应者较高的缓解率主要反映了肺功能正常化的较高比例。
在接受抗IL-5治疗的相当一部分患者中，抗IL-5治疗后FeNO水平降低，这与临床缓解相关。抗IL-5的早期FeNO反应可能潜在地用作生物标志物，以指导使用生物制剂实现重度哮喘疾病缓解的管理决策。
