Efficacy of tezepelumab in patients with perennial allergy grouped by specific immunoglobulin E thresholds and by age
M. Caminati1; A. W. Lindsley2; J. D. Spahn3; C. Ambrose4; JP. Llanos5; N. Martin6, 7; F. C. L. Hoyte8
1Department of Medicine, University of Verona, Verona, Italy; 2US Medical Affairs, Amgen, Thousand Oaks, United States of America; 3Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Wilmington, United States of America; 4Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, United States of America; 5Global Medical Affairs, Amgen, Thousand Oaks, United States of America; 6Cytel Inc., Waltham, United States of America; 7Biometrics, Late-stage Development, BioPharmaceuticals R&D, AstraZeneca, Waltham, United States of America; 8Division of Allergy and Immunology, National Jewish Health, Denver, United States of America
Background

In allergic asthma, presence of allergen-specific immunoglobulin Es (IgEs) indicates sensitization to that allergen and often implicates that allergen as a key symptoms trigger. A threshold of ≥0.35 kUA/L is commonly used to define a positive result, but higher concentrations may indicate a greater degree of sensitivity. Additionally, the incidence of allergic asthma is highest in early life and declines markedly after 35 years of age. In allergen-challenge provocation testing, a lower allergen exposure threshold correlates with a higher specific IgE level. Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin (TSLP). This post hoc analysis used pooled data from phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies to evaluate the efficacy of tezepelumab in patients with perennial allergy grouped by thresholds of specific IgE and by age.

Method

PATHWAY and NAVIGATOR were similarly designed, multicentre, randomized, placebo-controlled studies. Included patients (12–80 years old) received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks was assessed in patients identified at baseline as perennial aeroallergen-sensitized, grouped by specific IgE thresholds (≥1 specific IgE level ≥0.35, ≥0.70, ≥3.5 or ≥17.5 kUA/L) and by age (<35 and ≥35 years).

Results

Of the 1334 patients included (tezepelumab, n=665; placebo, n=669), 61% (815/1334) had ≥1 perennial allergen sensitization (≥0.35 kUA/L). Among patients who were <35 years old, 86% (184/215) had ≥1 specific perennial IgE level ≥0.35 kUA/L. Of those who were ≥35 years old, 56% (631/1119) had ≥1 specific perennial IgE level ≥0.35 kUA/L. Older patients had lower median total serum IgE and specific perennial IgE levels than younger patients (Table). When assessing a higher threshold of sensitivity, 64% (138/215) of patients aged <35 years old had ≥1 specific perennial IgE level ≥17.5 kUA/L versus 26% (296/1119) of those aged ≥35 years old. In both age groups, reductions in AAERs over 52 weeks with tezepelumab versus placebo were similar across all specific IgE threshold subgroups (Figure). 

Conclusion

Compared with placebo, tezepelumab consistently reduced exacerbations in patients with severe, uncontrolled asthma with sensitization to perennial aeroallergens, irrespective of age or the presence and severity of coexisting atopic (specific IgE threshold) status.