Background: Asthma treatment guidelines recommend corticosteroid (CS) increase to control symptoms and reduce exacerbations. This approach is potentially flawed as symptomatic asthma can occur without CS responsive type 2 (T2)-driven eosinophilic inflammation with potential for inappropriate high dose CS. We compared a biomarker strategy (BS) to adjust CS, using a composite score of T2 biomarkers (fractional exhaled nitric oxide (FeNO), blood eosinophils, serum periostin) with a standardised symptom/risk-based algorithm (control).
Methods: We have completed a randomised (ratio of 4:1/BS:control by an online pre-specified schedule), controlled, single-blind parallel group trial in adults (≥18y) with severe asthma and FeNO <45 ppb (ClinicalTrials.gov: NCT02717689). Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment arm specific algorithms. The primary outcome was proportion of patients with CS dose reduction in the intention-to-treat (ITT) principle (week 48). Secondary outcomes included severe exacerbation rate, lung function and asthma control.
Findings: In the ITT population (301 patients randomised: 240 BS, 61 control), the proportion of patients in BS on lower CS dose vs. control at week 48 was 28.4% vs. 18.5% (adjusted OR: 1.71; 95%CI 0.80, 3.63; p=0.165). In the per protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower CS dose at week 48 in the BS vs. control group (30.7% vs. 5.0%, respectively (OR: 11.48; 95%CI 1.35, 97.83; p=0.026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study arms and no loss of asthma control in BS patients who reduced their CS dose.
Interpretation: Biomarker based CS adjustment did not result in a greater proportion of patients reducing CS vs. control. Understanding the reasons for patients not following
treatment advice in both treatment strategies is an important area for future research. The prevalence of T2-biomarker low severe asthma was low
|Journal||The Lancet Respiratory Medicine|
|Publication status||Accepted - 01 Aug 2020|