Impact Of The 2022 Bronchodilator Responsiveness Criteria On Study Eligibility and Treatment Response To Inhaled Triple Therapy (BDP/FF/GB) In Moderate-To-Severe Asthma: A Post-Hoc Analysis Of TRIMARAN & TRIGGER.

<bold>Introduction:</bold> In most asthma trials, evidence of significant bronchodilator responsiveness (BDR) is required for eligibility. Typically, the 2005 ATS/ERS criteria are used, defining a positive BDR as an increase in FEV1 of 12% and 200 ml. In 2022, the ERS/ATS task force on the interpretation of lung function tests (Stanojevic S et al., Eur Respir J 2022;60:2101499) recommended defining a positive BDR as an increase in FEV1 or FVC of 10% relative to the predicted values. <bold>Objectives:</bold> We assessed the impact of applying the 2022 BDR criterion for FEV1 on subject eligibility and on the treatment response to BDP/FF/GB vs. BDP/FF in two large asthma clinical trials (Virchow JC et al., Lancet 2019;394:1737–49). <bold>Methods:</bold> The number (%) of eligible/non-eligible subjects at screening was calculated using each BDR criteria. We then assessed the treatment response to BDP/FF/GB vs BDP/FF in subjects who did not meet the novel BDR criteria. <bold>Results:</bold> Using the novel BDR criteria, 246 (21.4%) and 274 (24.0%) of subjects randomized would not have been eligible for enrollment in TRIMARAN and TRIGGER, respectively. Greater increase in pre-dose FEV1 at week 26 was observed with BDP/FF/GB vs. BDP/FF in the non-eligible subset compared to the overall study population in both studies (TRIMARAN: 112 ml and 57 ml; TRIGGER: 110 ml and 73 ml, respectively). <bold>Conclusion:</bold> The change in BDR criteria proposed in 2022 would have significantly restricted the enrolment in the TRIMARAN & TRIGGER trials, resulting in deselection of subjects who would particularly benefit from add-on LAMA to ICS/LABA.