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 patient...
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2025-01-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/11/1/00448-2024.full |
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| author | Kenta Nishi Hisako Matsumoto Hironobu Sunadome Tadao Nagasaki Tsuyoshi Oguma Noriyuki Tashima Yusuke Hayashi Satoru Terada Kyohei Morita Chie Yoshimura Yasuo Nishizaka Akiko Sano Takashi Iwanaga Hiroyuki Sano Ryuta Haraguchi Yuji Tohda Takahisa Kawaguchi Fumihiko Matsuda Toyohiro Hirai |
| author_facet | Kenta Nishi Hisako Matsumoto Hironobu Sunadome Tadao Nagasaki Tsuyoshi Oguma Noriyuki Tashima Yusuke Hayashi Satoru Terada Kyohei Morita Chie Yoshimura Yasuo Nishizaka Akiko Sano Takashi Iwanaga Hiroyuki Sano Ryuta Haraguchi Yuji Tohda Takahisa Kawaguchi Fumihiko Matsuda Toyohiro Hirai |
| author_sort | Kenta Nishi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1e2fe7aacc2a4c21b91be30676d7352b |
| institution | DOAJ |
| issn | 2312-0541 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj-art-1e2fe7aacc2a4c21b91be30676d7352b2025-08-20T03:02:16ZengEuropean Respiratory SocietyERJ Open Research2312-05412025-01-0111110.1183/23120541.00448-202400448-2024IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthmaKenta Nishi0Hisako Matsumoto1Hironobu Sunadome2Tadao Nagasaki3Tsuyoshi Oguma4Noriyuki Tashima5Yusuke Hayashi6Satoru Terada7Kyohei Morita8Chie Yoshimura9Yasuo Nishizaka10Akiko Sano11Takashi Iwanaga12Hiroyuki Sano13Ryuta Haraguchi14Yuji Tohda15Takahisa Kawaguchi16Fumihiko Matsuda17Toyohiro Hirai18 Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Osaka Red Cross Hospital, Osaka, Japan Department of Respiratory Medicine, Osaka Red Cross Hospital, Osaka, Japan Department of Respiratory Medicine, Osaka Red Cross Hospital, Osaka, Japan Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osaka, Japan Center for General Medical Education and Clinical Training, Kindai University Hospital, Osaka, Japan Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osaka, Japan Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osaka, Japan Kindai University Hospital, Osaka, Japan Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan 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.http://openres.ersjournals.com/content/11/1/00448-2024.full |
| spellingShingle | Kenta Nishi Hisako Matsumoto Hironobu Sunadome Tadao Nagasaki Tsuyoshi Oguma Noriyuki Tashima Yusuke Hayashi Satoru Terada Kyohei Morita Chie Yoshimura Yasuo Nishizaka Akiko Sano Takashi Iwanaga Hiroyuki Sano Ryuta Haraguchi Yuji Tohda Takahisa Kawaguchi Fumihiko Matsuda Toyohiro Hirai IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma ERJ Open Research |
| title | IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma |
| title_full | IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma |
| title_fullStr | IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma |
| title_full_unstemmed | IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma |
| title_short | IL1RL1 variant may affect the response to type 2 biologics in patients with severe asthma |
| title_sort | il1rl1 variant may affect the response to type 2 biologics in patients with severe asthma |
| url | http://openres.ersjournals.com/content/11/1/00448-2024.full |
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