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<0.0001).

CONCLUSION: This exploratory post-hoc analysis identified females achieved a greater benefit from biomarker-directed corticosteroid optimisation versus symptom-directed treatment.