REal worlD Effectiveness and Safety of Mepolizumab in a Multicentric Spanish Cohort of Asthma Patients Stratified by Eosinophils: The REDES Study

Abstract

Background: The efficacy of mepolizumab is well documented in severe eosinophilic asthma (SEA), although the stringent selection criteria adopted by SEA clinical trials limits the generalizability of results.

Objective: Our study evaluated the effectiveness and safety of mepolizumab in patients with SEA in Spain. The primary efficacy endpoint was the change in the rate of clinically significant asthma exacerbations 12 months after starting mepolizumab compared to the baseline rate in the 12 months prior to treatment. Patients were stratified by baseline blood eosinophil counts.

Methods: We conducted a multicentric observational cohort study of SEA patients treated with mepolizumab across 24 specialized hospital asthma units in Spain. Severe exacerbation rate, lung function, oral corticosteroid use (OCS) and asthma control test (ACT) were retrospectively collected and compared during the 12-month pre- and post-mepolizumab treatment. Adverse events were also investigated.

Results: A total of 318 patients with SEA were included (mean age: 56.6 years, 69.2% female). Exacerbation rates decreased by 77.5%, and 50.6% of patients did not suffer any exacerbations during the 12 months of treatment. The difference in forced expiratory volume in 1 s (FEV1) pre- and post-bronchodilator after starting mepolizumab was 0.21 (0.46) L (95% CI 0.14-0.27) (p < 0.001). Exacerbations and lung function significantly improved across all eosinophil subgroups. Among the 98 patients on OCS, 47.8% were able to discontinue this treatment and the mean daily dose was decreased by 59.9%. The baseline ACT score was 14.1, increasing by a mean (SD) of 6.7 points (1.9) at 12 months. Adverse events related to mepolizumab were uncommon.

Conclusions: This real-world study of SEA patients confirms that mepolizumab is effective in reducing clinically meaningful exacerbations, improving lung function, and decreasing OCS dependence and mean OCS dose at 12 months, irrespective of baseline eosinophil counts.

Fig. 1

Patient flowchart

Fig. 2

Mean number of total exacerbations 12 months pre- and post-mepolizumab initiation by baseline eosinophil sub-groups and thresholds

Fig. 3

Change in annual exacerbation rates pre- and post-mepolizumab initiation by exacerbation type. Three types of exacerbation types were considered: exacerbations requiring only corticosteroid, requiring emergency room (ER) visit and requiring hospitalization. Total exacerbations represent all exacerbations together, while exacerbations requiring ER/hospitalizations represent the sum of each individual category

Fig. 4

Mean and standard error for evolution of forced expiratory volume in 1 s (FEV1) pre- and post-bronchodilator use according to baseline eosinophil level. FEV1 before and after bronchodilators is expressed in (L) and as a percentage (%). The change in FEV1 represents the mean difference from baseline at 6 and 12 months

Fig. 5

Daily dose evolution of oral corticosteroid use (OCS; ranges and median daily dose of prednisone equivalent) in patients with maintenance corticosteroids at baseline. The left Y-axis represents the total percentages, which are based on the total number of patients with OCS treatment at baseline (n = 98). The right Y-axis represents the median OCS dose progression. The X-axis represents the three different assessment time points (baseline, 6 and 12 months). The colour gradients represent the OCS dose ranges, where the volume represents the percentage of patients within each range

Fig. 6

Evolution from baseline in Asthma Control Test (ACT) scores after mepolizumab initiation. Evolution and change in the mean ACT scores over the three different assessment time-points (baseline, 6 and 12 months) according to blood eosinophil counts at baseline. ACT score > 19 indicates well-controlled asthma