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Abstract
Background and importance The main difficulty in the treatment of severe allergic asthma lies in its heterogeneity. Currently, therapies have improved with the use of monoclonal antibodies such as omalizumab (Xolair), which acts by binding to the Cɛ3 domain of immunoglobulin E (IgE), so that it cannot bind to the FceR receptor and consequently the amount of free IgE responsible for the allergic response is reduced (Figure 1). Despite this, there is variability in the response to treatment and one of the possible causes is the presence of genetic polymorphisms.
Aim and objectives The objective was to determine if there is an association between Arg102Gly gene polymorphism of the Cɛ3 domain and omalizumab response.
Material and methods A retrospective cohort study was performed in a third-level hospital, including 70 patients with severe asthma who had received treatment with omalizumab for at least 1 year. Clinical variables were obtained using the ATHOS-Prisma clinical software and the polymorphism was analysed by real-time polymerase chain reaction (PCR) with TaqMan probes and Sanger sequencing. Response was evaluated according to the indications of the Spanish Guide for the Management of Asthma (GEMA) and the statistical analysis was carried out with R 3.0.1.
Results 70 patients were included in the study, of whom 64% were women (45/70) and 36% men (25/70). Average patient age was 52±15 years with a median treatment duration of 4 (2,6) years. 57% of the patients responded to the treatment according to the GEMA Guide compared to 43% who did not get a response. The bivariate analysis between response and Arg102Gly gene polymorphism of Cɛ3 domain showed that patients carrying Arg102Gly-C allele (p=0.0384; OR 2.97; 95% CI 1.07 to 8.94) presented better response to treatment with omalizumab. Specifically, the response was increased by 30% in patients with Arg102Gly-C allele.
Omalizumab mechanism of action
Conclusion and relevance The use of biological drugs has led to a significant improvement in these patients’ quality of life. However, identification of the correct therapy is a prognosis critical point. In this study, an allelic variant in C3 gene was positively associated with omalizumab treatment response. This discovery makes possible the approach to a personalised medicine that allows the improvement of prognosis in severe allergic asthma patients.
Conflict of interest No conflict of interest