Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma

Abstract

Purpose: Biomarkers, including blood eosinophils (EoS) and fractional exhaled nitric oxide (FeNO), may affect omalizumab outcomes in allergic asthma, but evidence in the literature remains mixed. This study assessed omalizumab outcomes in real-world patients with allergic asthma stratified by pretreatment biomarker levels. Methods: Patients with allergic asthma aged 12 years initiated on omalizumab with 12 months of data after index were identified in the Allergy Partners electronic medical records (2007e2018). Patients with 1 diagnosis of chronic obstructive pulmonary disease in combination with 10 pack-years of smoking, cystic fibrosis, Alpha-1 antitrypsin deficiency, bronchiectasis, interstitial lung disease, and sarcoidosis in the 12 months before or after index were excluded. Patients were stratified by pretreatment EoS (/<300 cells/mL) and FeNO (/<25 parts per billion). Outcomes, including Asthma Control Test (ACT) scores, forced expiratory volume in 1 second (FEV 1), and FEV 1 as a percentage of predicted value (FEV 1 % predicted), were compared using generalized estimating equations at 6 and 12 months after versus before index date in stratified patients with outcome measures available at both time periods. Findings: A total of 77 and 86 patients were stratified into the high and low EoS strata, respectively, and 56 patients into each of the intermediate-high and low FeNO strata. Compared with 6 months before index, mean difference (MD) in ACT scores at 6 months after index reached the minimally important difference of 3 points in high (MD ¼ 3.75; 95% CI, 2.05e5.45) and

Role of clinical biomarkers in predicting the effectiveness of omalizumab

“…We found that FeNO was not a useful biomarker to predict the effectiveness of omalizumab. Our results were similar to the results of a retrospective study 25 that enrolled 56 allergic asthma patients, and the results of the PROSPERO real-world study, 24 which was a prospective study that enrolled 806 patients with allergic asthma.…”

“…The PROSPERO study by Casale et al , 24 the retrospective study by Kavati et al , 25 and the STELLAIR study by Humbert et al 26 showed that peripheral blood eosinophils cannot be used as a biomarker for omalizumab responsiveness. However, in the EXTRA study, 23 the response to omalizumab therapy was better in the high peripheral blood eosinophil subgroup than in the low eosinophil subgroup, indicating that patients with a high eosinophil count may benefit from omalizumab therapy.…”

“…The literature reported that fractional exhaled nitric oxide (FeNO), blood eosinophil count, and forced expiratory volume in 1 s (FEV1) are clinical indicators for responsiveness to omalizumab. 20 – 23 Nevertheless, both prospective real-world 24 and retrospective studies 25 , 26 have found that biomarker levels before omalizumab treatment do not affect the response.…”

Omalizumab: An Optimal Choice for Patients with Severe Allergic Asthma

“…There are some studies which have not found an association between these biomarkers and the response to omalizumab [92,93,170]. However, the majority of the studies demonstrate such an association, with the high levels of blood eosinophils and FeNO and, to a lesser degree, of serum periostin to be associated with higher response rates to the treatment with omalizumab in terms of symptom and exacerbation control, OCS usage, hospital admissions and lung function [90,169,[171][172][173][174][175]. Moreover, histological and immunological studies of the airways have shown that omalizumab reduces the mucosal concentration of IgE and the tissue eosinophil cell density [176].…”

“…Patients with severe allergic asthma often experience a significant decline in lung function. Despite the fact that some studies have not found a significant improvement in forced expiratory volume in 1 s (FEV1) after the initiation of omalizumab [118,166,[183][184][185][186][187][188][189], the majority of the studies have exhibited a significant improvement in FEV1 after the initiation of omalizumab in asthmatic patients both as a whole [17,29,32,33,59,60,67,73,81,86,119,152,153,158,162,173,[190][191][192][193][194][195][196][197][198], and in specific groups such as children [199], obese patients [200], patients with fixed airway obstruction [201], patients with various co-morbidities [202], and even non-atopic patients with asthma [87]. Similar improvements after the initiation of omalizumab have also been observed in forced vital capacity (FVC) [33,203], FEV1/FVC ratio [59,73], peak expiratory flow (PEF) [19,86,…”