@misc{10481/93995,
year = {2024},
month = {7},
url = {https://hdl.handle.net/10481/93995},
abstract = {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.},
organization = {ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039) supported by
co-funding grants from the Biobank of the Hospital Universitario Virgen de las Nieves},
publisher = {MDPI},
keywords = {asthma},
keywords = {benralizumab},
keywords = {mepolizumab},
title = {SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma},
doi = {10.3390/ijms25158139},
author = {Rojo-Tolosa, Susana and Sánchez Martínez, José Antonio and Caballero Vázquez, Alberto and Pineda-Lancheros, Laura Elena and González Gutiérrez, María Victoria and Pérez Ramírez, Cristina and Jiménez Morales, Alberto and Morales García, Concepción},
}