Real-world biomarker variability and effects of biologics on severe asthma in Alberta

Abstract

Rationale: Guidelines recommend biomarker testing to phenotype patients with severe asthma (SA), to guide treatment. However, biomarker levels fluctuate, and individual responses to biologics are not fully understood. Objectives: This study estimated the proportion of patients experiencing biomarker variability and the real-world effectiveness of biologics in SA. Methods: A population-based retrospective cohort study was conducted using administrative data from Alberta, Canada (April 1, 2010 to March 31, 2020) for patients with SA. Year-to-year variability in biomarker levels was assessed using clinical thresholds (blood eosinophil count [EOS] ≥ 300 cells/µL; immunoglobin E [IgE] ≥ 30 IU/mL) to explore category switching. Incidence rate ratios of exacerbations were estimated by biomarker level. Associations between follow-up time with biologics exposure (bio-experience), biomarker levels and exacerbation rates were modeled. Results: Up to 28% of SA patients displayed year-over-year biomarker threshold switching for EOS and up to 12% for IgE. Severe exacerbation rates were higher with blood EOS count ≥300cells/µL or IgE ≥30 IU/mL. Bio-experience was associated with lower blood EOS versus pre-bio-experience (relative mean EOS: 0.53 [0.42-0.68]), persisting >1 year following discontinuation. Bio-experience was associated with a nearly 50% reduction in exacerbation risk after initiating biologics (IRR = 0.54 [0.48, 0.62]), regardless of comorbid status. Conclusions: Higher biomarker levels were associated with higher exacerbation rates, but a proportion of patients demonstrated variability, crossing clinical thresholds. Treatments with upstream agents targeting multiple pathways of inflammation may circumvent this issue. Biologics had real-world effectiveness in reducing SA biomarkers. Their persistent temporal effect provides a groundwork for exploring cost-effective biologics use.