Temporal trends in baseline severity and 12-month response to mepolizumab in severe asthma: The TYREX multicentre real-world study in Spain (2017–2024)

BACKGROUND AND OBJECTIVE: Although mepolizumab has demonstrated efficacy and effectiveness in the treatment of severe asthma, it is unknown whether the characteristics of patients starting this biologic have changed over the years and whether this impacts their response to mepolizumab. METHODS: TYREX was a multicenter, retrospective, observational study conducted in 24 asthma units across Spain to compare baseline clinical and demographic characteristics, and 12-month response to mepolizumab in two cohorts defined by the date of biologic initiation (cohort 1: 2017-2019 vs cohort 2: 2022-2024). RESULTS: Among the 446 patients included in the TYREX study, 191 were classified in cohort 1 and 108 in cohort 2. Cohort 1 had higher baseline exacerbation rates (3.45 vs. 2.40/year; p = 0.0002) and higher blood eosinophils (806 vs. 607 cells/μL; p = 0.0175). Twelve months after mepolizumab initiation, annual exacerbation rate were reduced to 0.46 in cohort 1 and to 0.51 in cohort 2, ACT scores increased from 14.23 to 21.84 vs. from 15.43 to 21.06; daily oral corticosteroid dependent patients dropped from 33.51% to 9.04% vs. from 12.96% to 2.78%; and clinical remission was achieved in 37.5% vs. 38.5% of patients after 12 months with mepolizumab. In multivariable analysis for 4-domain clinical remission (n = 108), higher baseline ppFEV1 increased the odds of remission while maintenance OCS use decreased them (Figure. 3). In the 3-domain remission model (n = 198), CRSwNP and higher baseline blood eosinophil count increased the odds of remission, whereas maintenance OCS use decreased them (Figure. 3). CONCLUSION: The decrease over time in severity and blood eosinophilia in asthma patients starting mepolizumab has not shown any impact on the clinical response to the drug.