IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma.

Background: Asthma is a heterogeneous disease with variable response to treatment. Genetic backgrounds are involved in the severity of type 2 asthma, but their effects on responses to biologics remain unknown. This study aimed to clarify the role of genetic factors in response to biologics in patients with severe asthma.

Methods: Adults with severe asthma receiving biologics were enrolled in this multicentre, observational, real-world study. The responses to biologics were evaluated using Physicians' Global Evaluation of Treatment Effectiveness (GETE). Optimal biologic for each patient was also determined based on the best GETE score for the biologic used or currently used biologic. Three single nucleotide polymorphisms (IL1RL1, rs1420101; IL4RA, rs8832; and TSLP rs1837253) were examined.

Results: Among the 113 patients analysed, 53 (46.9%) had an excellent GETE score for at least one biologic. These patients with an excellent GETE score for at least one biologic, particularly for benralizumab, had the risk genotype of rs1420101 more frequently than the remaining patients, independent of the clinical demographics. Regarding the optimal biologic for each patient, anti-IL-5 drugs were optimal for patients with the rs1420101 TT or rs8832 GG genotype. Furthermore, dupilumab was similarly effective, regardless of the risk genotypes examined in this study.

Conclusion: IL1RL1 rs1420101 TT genotype and/or IL4RA rs8832 GG genotype may predict an excellent or optimal response to biologic therapy in each patient, particularly to anti-interleukin-5 targeted therapy. The elucidation of genetic predisposition may improve the management of severe asthma in the era of biologics.