LAUSR

RATIONALE Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts (BECs) and fractional exhaled nitric oxide (FeNO) levels, and irrespective of allergy status, in the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies. OBJECTIVES To examine the efficacy and safety of tezepelumab in additional clinically relevant subgroups using pooled data from PATHWAY and NAVIGATOR. METHODS PATHWAY and NAVIGATOR were randomized, double-blind, placebo-controlled studies with similar designs. This pooled analysis included patients with severe, uncontrolled asthma (PATHWAY, 18-75 years old; NAVIGATOR, 12-80 years old) who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks and secondary outcomes were calculated in the overall population and in subgroups defined by inflammatory biomarker levels or clinical characteristics. MEASUREMENTS AND MAIN RESULTS Overall, 1,334 patients were included (tezepelumab, n=665; placebo, n=669). Tezepelumab reduced the AAER (rate ratios; 95% confidence intervals) versus placebo by 60% (0.40; 0.34, 0.48) in the overall population, and clinically meaningful reductions in exacerbations were observed in tezepelumab-treated patients with type 2-high and type 2-low disease by multiple definitions. Tezepelumab reduced exacerbation-related hospitalization or emergency department visits and improved secondary outcomes compared with placebo overall and across subgroups. The incidence of adverse events was similar between treatment groups. CONCLUSIONS Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups.