Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background.
biological therapy
clinical trials
genome-wide association studies
inflammatory diseases
rheumatic diseases
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
05 10 2023
05 10 2023
Historique:
received:
23
03
2023
revised:
15
08
2023
accepted:
15
08
2023
medline:
9
10
2023
pubmed:
3
9
2023
entrez:
2
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37659414
pii: S0002-9297(23)00286-0
doi: 10.1016/j.ajhg.2023.08.010
pmc: PMC10577077
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1817-1824Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.Z., C.H., N.H., C.T., M.W., A.R., R.M., M.T.B., J.Z., E.F., and M.V. are employees and stock owners of Novartis AG or its subsidiaries. Other authors, including K.S., C.H.K., L.S., D.W., and S.G. were funded by the BDI-Novartis Collaboration for AI in Medicine, which is funded by a grant from Novartis AG. Novartis AG manufactures and markets secukinumab and has an ongoing commercial interest in its success.
Références
J Affect Disord. 2022 May 1;304:1-11
pubmed: 35151671
Ther Adv Musculoskelet Dis. 2022 Apr 29;14:1759720X221090310
pubmed: 35510168
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Genet Epidemiol. 2016 Feb;40(2):144-53
pubmed: 26659945
Ann Rheum Dis. 1990 Nov;49(11):916-20
pubmed: 2256738
Nat Rev Genet. 2013 Sep;14(9):661-73
pubmed: 23917628
Ann Rheum Dis. 2013 Aug;72(8):1375-81
pubmed: 23233654
Ann Rheum Dis. 2021 May;80(5):558-565
pubmed: 33310728
PLoS One. 2011 May 12;6(5):e19416
pubmed: 21589913
PLoS One. 2018 Apr 3;13(4):e0195325
pubmed: 29614084
PLoS Med. 2020 Oct 30;17(10):e1003348
pubmed: 33125391
Gut. 2019 Sep;68(9):1537-1540
pubmed: 31270165
Nat Genet. 2012 Dec;44(12):1341-8
pubmed: 23143594
Arthritis Rheumatol. 2017 Jun;69(6):1144-1153
pubmed: 28217871
Pharmacogenomics J. 2018 Sep;18(5):657-664
pubmed: 30166627
Front Immunol. 2020 Nov 17;11:594735
pubmed: 33281823
Clin Transl Gastroenterol. 2016 Jan 07;7:e135
pubmed: 26741065
Dermatologica. 1978;157(4):238-44
pubmed: 357213
Nat Genet. 2013 Jul;45(7):730-8
pubmed: 23749187
Br J Rheumatol. 1996 Sep;35(9):867-73
pubmed: 8810670
Rheumatology (Oxford). 2022 Nov 2;61(11):4305-4313
pubmed: 35137002
Microbes Infect. 2019 Jun - Jul;21(5-6):246-253
pubmed: 31252215
Nat Rev Rheumatol. 2022 Dec;18(12):725-733
pubmed: 36216923
Genome Med. 2020 May 18;12(1):44
pubmed: 32423490
Genome Med. 2020 Nov 25;12(1):106
pubmed: 33239102
Genome Biol. 2021 Jun 21;22(1):183
pubmed: 34154633
Am J Hum Genet. 2015 Dec 3;97(6):816-36
pubmed: 26626624
Pharmacogenomics J. 2023 Jan;23(1):1-7
pubmed: 36243888
Rheumatology (Oxford). 2016 Jan;55(1):49-55
pubmed: 26268815
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Arthritis Res Ther. 2017 Dec 22;19(1):285
pubmed: 29273067
J Eur Acad Dermatol Venereol. 2020 Jun;34(6):1174-1185
pubmed: 31919937
Ann Rheum Dis. 2018 Jun;77(6):890-897
pubmed: 29550766
Nat Commun. 2022 May 25;13(1):2922
pubmed: 35614072
N Engl J Med. 2014 Jul 24;371(4):326-38
pubmed: 25007392
Hum Hered. 2007;63(2):111-9
pubmed: 17283440
Nat Commun. 2022 Sep 8;13(1):5278
pubmed: 36075892
Nat Commun. 2017 May 24;8:15382
pubmed: 28537254
Br J Dermatol. 2018 Nov;179(5):1072-1080
pubmed: 29704432
Expert Opin Biol Ther. 2021 Feb;21(2):259-270
pubmed: 33297781
Gastroenterology. 2020 Jan;158(1):189-199
pubmed: 31600487
Nat Rev Rheumatol. 2022 Mar;18(3):123-124
pubmed: 35087234
J Transl Med. 2021 Jun 5;19(1):245
pubmed: 34090480