Real-World Effectiveness of Biologic Therapies in Severe Asthma Patients Ineligible for Phase 3 Randomised Controlled Trials (RCTs)

Abstract

Background Previous research has shown most patients in realworld severe asthma populations would not be eligible for relevant biologics RCTs. Although observational evidence has confirmed the effectiveness of biologics in unselected realworld populations, whether specific RCT inclusion and exclusion criteria affect response remains unclear. Methods Inclusion and exclusion criteria from 11 landmark phase 3 asthma biologics RCTs were reviewed to identify themes in inclusion/exclusion criteria, and the median stringency criteria within each theme characterised. Patients within the UK Severe Asthma Registry (UKSAR) with at least one year of follow-up on biologics were assessed as to whether they would satisfy inclusion/exclusion for each identified theme. Regression models were undertaken to assess whether composite biologic response, defined as meeting the NICE criteria of a 50% reduction in exacerbations or a 50% reduction in maintenance oral corticosteroids (mOCS), was non-inferior in patients ineligible by each theme. Superiority analyses and domain specific (ACQ improvement, exacerbation reduction, lung function improvement, mOCS elimination) responses were also analysed. Results 1421 adult patients with severe asthma in UKSAR from 13 specialist centres were included in this analysis. Non-inferiority of composite biologic response was demonstrated for all eligibility criteria except medication adherence. In superiority analyses, patients ineligible by adherence theme had a significant lower Odds Ratio (OR) for composite biologics response of 0.37 (95% CI 0.20, 0.68) whilst patients ineligible by (low) baseline asthma symptom score (ACQ<1.5) had a significantly higher OR for response of 2.09 (1.31, 3.32). Additionally, being ineligible by some criteria was associated with significant differences in several domain specific responses (table 1), e.g. non-obstructive lung function at baseline was associated with an inferior lung function domain response. Discussion In this multi-centre analysis, ineligibility by typical RCT inclusion/exclusion themes was generally not associated with inferior biologic responses. While strict inclusion/exclusion criteria are needed for RCTs leading to drug licensing, our results show that asthma biologics are effective in a broad range of patients, many who would not have met clinical trial criteria. (Table Presented).