Predictive Biomarkers for Asthma Therapy

Medrek, Sarah; Parulekar, Amit; Hanania, Nicola A.

doi:10.1007/s11882-017-0739-5

Cited by 45 publications

(36 citation statements)

References 110 publications

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“…Endotyping has gained prominence as the identification of a patient subgroup defined by the presence of a biological mechanism . Recently, biological treatments for asthma have been developed using biomarkers to identify patients with specific mechanisms (ie endotypes) . The use of both clinical phenotype information and biomarkers to select patients for novel anti‐inflammatory treatments aligns with the precision medicine strategy that takes an individualized approach to optimize treatment.…”

Section: Discussionmentioning

confidence: 99%

A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild‐to‐moderate asthma

Ortega

Fitzgerald

Raghupathi

et al. 2019

Clin Experimental Allergy

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Background: GB001 is an oral antagonist of the prostaglandin D2 receptor that may inhibit recruitment and activation of airway eosinophils, reducing airway inflammation.Objective: To assess GB001 safety, efficacy and pharmacokinetics from a Phase 2 study and explore the association between type 2 biomarkers (fractional exhaled nitric oxide and blood eosinophils) and asthma control markers following GB001 administration. Methods:A randomized, placebo-controlled, double-blind study evaluating 36 patients with mild-to-moderate atopic asthma. Patients receiving fluticasone propionate ≤500 mcg/day or equivalent were randomized (2:1) to GB001 (30 mg) or placebo once daily for 28 days. Safety, pharmacokinetics, forced expiratory volume in 1 second, asthma control questionnaire and rescue medication use were assessed. Clinical outcomes were analysed post hoc by baseline fractional exhaled nitric oxide (<35 and ≥35 ppb) and blood eosinophil (<250 and ≥250 cells/µL) subgroups. Results: GB001 was well tolerated and rapidly absorbed with a 14.5-hour terminal half-life. Overall, GB001 demonstrated greater improvement relative to placebo in forced expiratory volume in 1 second at Day 28 (102 mL [95% CI: −110, 314]). Greater effects on forced expiratory volume in 1 second were observed in the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups (207 mL [95% CI: −283, 698];133 mL [95% CI: −422, 687], respectively). These effects were observed as early as Day 2 (229 mL [95% CI: −170, 628]; 163 mL [95% CI: −223, 550] for the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups, respectively) and were sustained through treatment completion. Conclusion and clinical relevance: GB001 was well tolerated, with the estimated half-life supporting once-daily (QD) dosing. GB001 may have a rapid and sustainedThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Discussionmentioning

confidence: 99%

A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild‐to‐moderate asthma

Ortega

Fitzgerald

Raghupathi

et al. 2019

Clin Experimental Allergy

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“…25 For instance, when data from patients only treated with omalizumab were considered in the Study of Omalizumab (Xolair) in Subjects with Moderate to Severe Persistent Asthma (EXTRA), no substantial difference in exacerbation frequency between the high and low EoS and FeNO subgroups were observed, suggesting that all patients can benefit from omalizumab treatment irrespective of biomarker status. 25 Literature has reported that other biomarkers, such as IgE, 35e37 periostin, 38 C-X-C motif chemokine 10, 39 and interleukin-12, 39 may also be of importance for patients treated with omalizumab.…”

Section: Discussionmentioning

confidence: 99%

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

Kavati

Zhdanava

Ortiz

et al. 2019

Clinical Therapeutics

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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

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“…However, bronchoscopy in asthmatics is impractical and not available for most clinicians. 10,20,21 Their ease of sampling makes them an appealing surrogate for airway samples. Sputum eosinophil levels may vary over time and can be influenced by the use of inhaled corticosteroids.…”

mentioning

confidence: 99%

“…19 Blood eosinophils fit criteria as a clinically useful biomarker: measures are accessible at point of care and predict response to interventions. 10,20,21 Their ease of sampling makes them an appealing surrogate for airway samples. 22 Blood levels were used for the first large-scale study demonstrating efficacy of anti-IL-5 treatment 18 and have been used for subsequent studies.…”

mentioning

confidence: 99%

Variability of blood eosinophils in patients in a clinic for severe asthma

Rakowski

Zhao

Liu

et al. 2019

Clin Experimental Allergy

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Background: Blood eosinophils are used to determine eligibility for agents targeting IL-5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation.Objective: To characterize variability and patterns of variability of blood eosinophil levels in a real-world clinic for severe asthmatics.Methods: Retrospective review of blood eosinophils measured over a 5-year period in patients enrolled in an urban clinic. Repeated measures of blood eosinophil levels in individuals were evaluated, and cluster analysis was performed to characterize patients by eosinophil patterns. Clinical characteristics associated with eosinophil levels and patterns of variability were analysed. Results:Patients treated in the Bellevue Hospital Asthma Clinic within a 3-month period were identified (n = 219). Blood eosinophil measures were obtained over the previous 5 years. Only 6% (n = 13) of patients had levels that were consistently above 300 cells/μL. Nearly 50% (n = 104) had eosinophil levels that traversed the threshold of 300 cells/μL. In contrast, 102 (46%) had levels that never reached the threshold of 300 cells/μL. Cluster analyses revealed three clusters with differing patterns of levels and variability. There was a suggestion of decreased clinical control and increased atopy in the cluster with the greatest variability in blood eosinophil measures. Conclusion:In an urban clinic for patients referred for uncontrolled asthma, blood measures of eosinophils were variable and showed differing patterns of variability.These data reinforce the need to perform repeated eosinophil blood measures for appropriate designation for therapeutic intervention.

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Predictive Biomarkers for Asthma Therapy

Cited by 45 publications

References 110 publications

A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild‐to‐moderate asthma

A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild‐to‐moderate asthma

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

Variability of blood eosinophils in patients in a clinic for severe asthma

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