Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background
Response to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseas...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2023
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| _version_ | 1797112122096746496 |
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| author | Zhang, K Shestopaloff, K Hollis, B Kwok, C Hon, C Hartmann, N Tian, C Wozniak, M Santos, L West, D Gardiner, S Mallon, A-M Readie, A Martin, R Nichols, T Beste, M Zierer, J Ferrero, E Vandemeulebroecke, M Jostins-Dean, L |
| author_facet | Zhang, K Shestopaloff, K Hollis, B Kwok, C Hon, C Hartmann, N Tian, C Wozniak, M Santos, L West, D Gardiner, S Mallon, A-M Readie, A Martin, R Nichols, T Beste, M Zierer, J Ferrero, E Vandemeulebroecke, M Jostins-Dean, L |
| author_sort | Zhang, K |
| collection | OXFORD |
| description | Response to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseases. Using changes in disease activity scores across 5,218 genotyped individuals from 19 clinical trials across four indications (psoriatic arthritis, psoriasis, ankylosing spondylitis, and rheumatoid arthritis), we tested whether genetics predicted response to secukinumab. We did not find any evidence of association between treatment response and common variants, imputed HLA alleles, polygenic risk scores of disease susceptibility, or cross-disease components of shared genetic risk. This suggests that anti-IL17 therapy is equally effective regardless of an individual’s genetic background, a finding that has important implications for future genetic studies of biological therapy response in inflammatory diseases. |
| first_indexed | 2024-03-07T08:19:45Z |
| format | Journal article |
| id | oxford-uuid:266c7629-a0b6-4812-b1a8-1308f7cb3775 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:19:45Z |
| publishDate | 2023 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:266c7629-a0b6-4812-b1a8-1308f7cb37752024-01-23T11:30:58ZResponse to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic backgroundJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:266c7629-a0b6-4812-b1a8-1308f7cb3775EnglishSymplectic ElementsCell Press2023Zhang, KShestopaloff, KHollis, BKwok, CHon, CHartmann, NTian, CWozniak, MSantos, LWest, DGardiner, SMallon, A-MReadie, AMartin, RNichols, TBeste, MZierer, JFerrero, EVandemeulebroecke, MJostins-Dean, LResponse to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseases. Using changes in disease activity scores across 5,218 genotyped individuals from 19 clinical trials across four indications (psoriatic arthritis, psoriasis, ankylosing spondylitis, and rheumatoid arthritis), we tested whether genetics predicted response to secukinumab. We did not find any evidence of association between treatment response and common variants, imputed HLA alleles, polygenic risk scores of disease susceptibility, or cross-disease components of shared genetic risk. This suggests that anti-IL17 therapy is equally effective regardless of an individual’s genetic background, a finding that has important implications for future genetic studies of biological therapy response in inflammatory diseases. |
| spellingShingle | Zhang, K Shestopaloff, K Hollis, B Kwok, C Hon, C Hartmann, N Tian, C Wozniak, M Santos, L West, D Gardiner, S Mallon, A-M Readie, A Martin, R Nichols, T Beste, M Zierer, J Ferrero, E Vandemeulebroecke, M Jostins-Dean, L Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
| title | Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
| title_full | Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
| title_fullStr | Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
| title_full_unstemmed | Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
| title_short | Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
| title_sort | response to anti il17 therapy in inflammatory disease is not strongly impacted by genetic background |
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