Mepolizumab for severe eosinophilic asthma – A one-year real life Portuguese study

Brás, Rita; Paulino, Marisa; Varandas, Cláudia; Coutinho, C; Silva, M I; Limão, Rita; Costa, Célia; Alonso, E Montecatine; Pedro, Elisa; Mendes, Ana

doi:10.1016/j.pulmoe.2021.05.007

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…The results of our study resemble these data, with a 74% reduction in exacerbations requiring emergency or hospitalization and a significant improvement in mean FEV1 of 10.3%. Real-life studies also reported improvements in lung function, asthma control, reduced the usage of OCS bursts, and maintenance OCS, and decreased eosinophil counts and exacerbations [29,31,[42][43][44][45][46][47]. Among these studies, we found a systematic review by Israel E. et al (2021) reflecting similar results in both prospective and retrospective studies [42].…”

Section: Discussionsupporting

confidence: 70%

“…The 73% (p = 0.004) and 83% (p values not reported) showed reductions in the rate of exacerbations requiring hospitalization; 27% to 84% had discontinued maintenance OCS and from 32% to 100% had reduced the initial maintenance dose (p < 0.001); lung function improved by 3% to 8% (p < 0.05); reductions in blood eosinophilic counts from 69% to 92% (p < 0.05); and changes in ACT from 5 to 8 points [42]. However, there are studies in which an improvement in lung function was not achieved, which may be due to the difference in population, history of smoking, or smaller sample size [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

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Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study

Rojo-Tolosa

González-Gutiérrez

Jiménez-Gálvez

et al. 2023

IJMS

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Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study

Rojo-Tolosa

González-Gutiérrez

Jiménez-Gálvez

et al. 2023

IJMS

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SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma

Rojo-Tolosa,

Sánchez-Martínez,

Caballero-Vázquez

et al. 2024

IJMS

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The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06–30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24–14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04–1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94–6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71–76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10−19–NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19–269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05–16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22–20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58–91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7–75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9–112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16–73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

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Mepolizumab for severe eosinophilic asthma – A one-year real life Portuguese study

Cited by 2 publications

References 6 publications

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study

SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma

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