Type 2 Biomarkers Define a Prevalent Phenotype in Moderate-to-Severe, Uncontrolled Asthma Patients: A Pooled Analysis from Lebrikizumab All-Comers Phase 2 Trials

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.