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

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 (rs4143832, rs17690122), (rs11739623, rs4705959), (rs1420101, rs17026974, rs1921622), (rs4857855), (rs12619285), (rs1801274), (rs3219018, rs1050501), (rs10127939, rs396991), (rs2251746, rs2427837), (rs1441586, rs573790, rs569108), and (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 rs1054485-T ( = 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 ( = 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 ( = 0.002; OR = 1.10; 95% CI = 1.04-1.18), rs569108-AA ( < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and rs2427837-A ( = 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 rs1054485-T ( = 0.073; OR = 1.3 × 10; 95% CI = 1.8 × 10-NA), rs569108-AA ( = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies ( = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex ( = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis ( = 0.027; OR = 9.16; 95% CI = 1.58-91.4), rs12619285-AA ( = 0.019; OR = 9.1; 95% CI = 1.7-75.78), rs4143832-T ( = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and rs1441586-C ( = 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.