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Type 2 Biomarkers Define a Prevalent Phenotype in Moderate-to-Severe, Uncontrolled Asthma Patients: A Pooled Analysis from Lebrikizumab All-Comers Phase 2 Trials
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Phillip E. Korenblat, MD, FAAAAI, Nicola A. Hanania, MD, Jonathan Corren, MD, Julie K. Olssen, MD, MS, Nikhil Kamath, MD, Sarah Gray, PhD, Nicolas Martin, Cecile T.J. Holweg, PhD, John G. Matthews, MB, BS, MRSCP, PhD, Susan L. Limb, MD, Stephan Korom
Rationale: With increasing recognition of the heterogeneity of severe asthma, better understanding of underlying endotypes is needed to identify patients for targeted therapies. By enrolling a broad population of moderate-to-severe uncontrolled asthma patients, we are able to analyze the prevalence of key Type 2 biomarkers in a population not enriched by biomarker or medical history.

Methods: We analyzed baseline distribution of key Type 2 biomarkers in pooled data from three Phase 2 lebrikizumab trials in 659 moderate-to-severe asthma patients (NCT00930163/NCT01545440/NCT01545453). Key eligibility criteria included treatment with ICS (200–2000 µg/day fluticasone propionate or equivalent) and ≥1 additional controller, uncontrolled asthma (ACQ-5 ≥1.5), pre-bronchodilator FEV1 40–80% predicted and ≥12% FEV1 reversibility. Patients were not excluded based on history of exacerbations or biomarker values.

Results: The key Type 2 biomarkers and cut-off values assessed in this post hoc analysis were serum periostin (≥50 ng/mL), blood eosinophils (≥300 cells/µL) and FeNO (≥30 ppb). Based on these cut-offs, 46%, 35% and 33% of patients were high for periostin, blood eosinophils and FeNO, respectively. There were 68% patients high for any Type 2 biomarker, 23% high for any two, and 11% high for all three. Overall, 18% of asthma patients were high for serum periostin only, 9% high for blood eosinophils only and 7% high for FeNO only.

Conclusions: In a pooled analysis of three trials designed to evaluate the effects of lebrikizumab treatment in moderate-to-severe uncontrolled asthma, 68% of patients had evidence of Type 2 inflammation using the specified cut-off values for periostin, blood eosinophils and FeNO.