DIFFERENCES IN ELIGIBILITY CRITERIA AND BASELINE PATIENT CHARACTERISTICS AMONGST TRIALS OF BIOLOGIC THERAPIES IN ASTHMA

Abstract

Introduction The understanding of asthma pathophysiology has evolved over time, impacting investigation of asthma biologics. Differences in eligibility criteria amongst trials for patients with diverse asthma severity and phenotypes have resulted in relevant differences in baseline characteristics. A systematic literature review explored these differences. Methods PubMed, EMBASE, Cochrane, ClinicalTrials.gov, and conferences were searched from 2003 onwards. Randomized controlled trials (RCTs) were included with: ≥24 weeks’ duration; biologic (omalizumab [OMA]/dupilumab [DUPI]/benralizumab [BENRA]/mepolizumab [MEPO]/reslizumab [RESLI]) + daily high-dose ICS + ≥1 controller; adults ≥18 years with moderate/severe uncontrolled asthma and evidence of Type 2 inflammation (eg, blood eosinophils). Results 27 RCTs (9 OMA/3 DUPI/6 BENRA/7 MEPO/2 RESLI) were included. Overall, BENRA/MEPO/RESLI trials enrolled patients with more severe asthma than OMA/DUPI (Table 1). Per inclusion criteria, the number of prior exacerbations was higher in BENRA/MEPO versus OMA/DUPI/RESLI trials. Baseline blood eosinophil levels varied between trials, but were highest in RESLI. There was a trend towards higher baseline FEV1 in OMA/RESLI trials compared with others. Most patients received medium/high dose ICS + LABAs, with more patients in MEPO trials receiving maintenance OCS. Conclusions Transitivity, an important assumption in network meta-analysis (NMA), requires populations and study designs be sufficiently similar or have differences that can be adjusted for by accepted methods. Substantial heterogeneity in baseline characteristics existed between trials of asthma biologics and OMA. These characteristics are potential treatment effect modifiers with limited evidence for adjustment. Therefore, comparison of OMA to other asthma biologics through NMA is not clinically valid and inconsistent with best practices. Table 1. Summary of eligibility criteria and baseline patient characteristics across randomized controlled trials of biologic agents in moderate-to-severe asthma.