A randomised trial of a T2-composite-biomarker strategy adjusting corticosteroidtreatment in severe asthma, a post- hoc analysis by sex.

Background Approximately 5–10% of patients with asthma have severe disease with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex. Objectives To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid treatment in patients with severe asthma compared to standard care. Methods Post-hoc analysis stratifying patient outcomes by sex of a 48-week, multicentre, randomised controlled clinical trial comparing a biomarker-defined treatment algorithm with standard care. The primary outcome was the proportion of patients with a reduction in corticosteroid treatment (inhaled (ICS) and oral (OCS) corticosteroids). Secondary outcomes included exacerbation rates, hospital admissions and lung function. Results Of 301 patients randomised; 194 (64.5%) were females and 107 (35.5%) were males. The biomarker algorithm led to a greater proportion of females being on a lower corticosteroid dose vs standard care which was not seen in males (effects estimate females: 3.57, 95% CI: 1.14, 11.18 vs. males 0.54, 95% CI: 0.16, 1.80). In T2-biomarker low females, reducing corticosteroid dose was not associated with increased exacerbations. Females scored higher in all ACQ-7 domains, but with no difference when adjusted for BMI/ anxiety and/or depression. Dissociation between symptoms and T2-biomarkers were noted in both sexes, with a higher proportion of females being symptom high/T2-biomarker low (22.8% vs. 15.6%; p=0.0002), whereas males were symptom low/T2-biomarker high (11.4% vs. 22.3%; p Conclusion This exploratory post-hoc analysis identified females achieved a greater benefit from biomarker-directed corticosteroid optimisation versus symptom-directed treatment.</p