(321) DARWIN EU® - Background Rates of Outcomes of Interest in Patients with Severe Asthma

Background: Safety results of a randomised clinical trial (RCT) in patients with severe asthma showed differences in rates of serious adverse events between treatment arms. To contextualise these differences, a non-interventional study was requested by the EMA to generate background rates of selected health outcomes in real-world data using the in- and exclusion criteria from the RCT.

Objectives: To estimate incidence rates (IR) of overall mortality, fatal infections, fatal cardiovascular events and of serious cardiovascular events.

Methods: Retrospective cohort study in routinely collected health data from 5 databases during 2015-2022. Primary care databases were Clinical Practice Research Datalink GOLD (CPRD GOLD, UK), Integrated Primary Care Information Project (IPCI, the Netherlands) and Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP, Spain). Other sources were the Estonian Biobank (EBB, Estonia), and the hospital database of Institut Municipal Assistència Sanitària Information System (IMASIS, Spain). Inclusion criteria were asthma diagnosis, use of at least 12 months medium dose inhaled corticosteroids (ICS), 12 weeks high dose ICS with additional maintenance asthma controller, and at least two asthma exacerbation in the previous year. In a second study cohort, patients with comorbidities were excluded. As in the RCT, IRs were estimated during the first and second year after study entry, for outcomes of interest. IRs were only calculated when the number of events was 5 or higher.

Results: From the total databases population of more than 28 million persons, 26,584 individuals with severe asthma were identified (cohort 1) of which 4,122 fulfilled the criteria of no comorbidities (cohort 2). No patients fulfilling in and exclusion criteria were identified in IMASIS.
For all-cause mortality in cohort 1, IR in the first year ranged between 16-30/1,000 PY for the primary care databases and was 58/1,000 PY in EBB. Similar rates were found in the second year. Because of the small size of cohort 2, mortality rates could only be calculated in CPRD GOLD, resulting in 6 and 5/1,000 PY in the first and second year respectively.
For serious cardiovascular (CV) events in cohort 1, IR in the first year ranged between 11-41/1,000 PY for the primary care databases and was 202/1,000 PY in EBB. Rates in the second year were lower. For cohort 2, IR in CPRD GOLD was 4/1,000 PY in both years and in SIDIAP 16 and 17/1,000 PY in the first and second year respectively. For other databases, numbers were too low to be reported.

Conclusions: This study provides insight into the background rates of major CV events and mortality in patients with severe asthma, particularly those who share clinical profiles like participants in RCTs.