Abstract
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 multicenter, 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-IL-5 targeted therapy. The elucidation of genetic predisposition may improve the management of severe asthma in the era of biologics.
Footnotes
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Conflict of interest: H. Matsumoto reports lecture fees from AstraZeneca, GSK, Sanofi, Novartis, and Kyorin unrelated to the submitted work. H. Sunadome reports grants from Philips Japan, grants from ResMed, grants from Fukuda Denshi, and grants from Fukuda Lifetec Keiji unrelated to the submitted work. T. Oguma reports receiving lecture fees from AstraZeneca and GlaxoSmithKline unrelated to the submitted work. K. Morita reports receiving lecture fees from AstraZeneca, Novartis Pharmaceuticals, Sanofi, and GlaxoSmithKline unrelated to the submitted work. Y. Tohda reports receiving study funding from AstraZeneca, grants from Boehringer Ingelheim, Kyorin Pharmaceutical, and Taiho, consulting fees from AstraZeneca, and lecture fees from AstraZeneca K.K., Kyorin Pharmaceutical Co., Ltd, Boehringer Ingelheim Co., Ltd, Daiichi Sankyo Co., Ltd, Sanofi K.K., and GlaxoSmithKline K.K unrelated to the submitted work. T. Hirai reports receiving lecture fees from AstraZeneca K.K., Sanofi K.K., and GSK plc unrelated to the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.
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- Received May 2, 2024.
- Accepted July 24, 2024.
- Copyright ©The authors 2024
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