DARWIN EU® - Background rates of clinical outcomes of interest in patients with severe asthma

<bold>Background:</bold> Safety results of an RCT in severe asthma showed differences in rates of serious adverse events between treatment arms. An observational study was <italic>requested by the EMA</italic> to generate background incidence rates (IRs) of selected outcomes (overall mortality, fatal and serious cardiovascular (CV) events). <bold>Methods:</bold> Retrospective cohort study using health data from 5 databases (DBs) during 2015- 2022. Primary Care DBs were CPRD GOLD (UK), IPCI (Netherlands) and SIDIAP (Spain). Other DBs were the Estonian Biobank (EBB) and IMASIS (hospital DB)(Spain). Inclusion criteria were diagnosis of <italic>asthma</italic>, use of at least 12 months <italic>medium dose ICS</italic> (of which at least 12 weeks of <italic>high dose ICS + other asthma controller</italic>), and <italic>at least 2 asthma exacerbations</italic> in the previous year. In a subcohort, patients with comorbidities were excluded. <bold>Results:</bold> From the total population of ≥28 millions, 26,584 patients with severe asthma were identified (main cohort). Among these, 4,122 fulfilled the criteria for the subcohort. IRs of all-cause mortality in the 1^st year was between 16-30/1,000 PY for GP DBs and was 58/1,000 PY in EBB. Similar rates were found in the 2^nd year. For the subcohort, mortality rates could only be calculated in CPRD GOLD, resulting in 6 and 5/1,000 PY in the 1^st and 2^nd year. For serious CV events, IRs in the 1^st year were between 11-41/1,000 PY for the GP DBs and was 202/1,000 PY in EBB. Rates in the 2^nd year were lower. For the subcohort, IR in CPRD GOLD was 4/1,000 PY in both years and 16 and 17/1,000 PY in the 1^st and 2^nd year for SIDIAP. <bold>Conclusion:</bold> This study provides insight into the background rates of mortality and major CV outcomes in patients with severe asthma.