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Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene: results from a multicentre study of four European psoriasis cohorts.

التفاصيل البيبلوغرافية
العنوان: Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene: results from a multicentre study of four European psoriasis cohorts.
المؤلفون: van Vugt LJ; Department of Dermatology, Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands.; Radboud Institute for Health Sciences (RIHS), Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands., van den Reek JMPA; Department of Dermatology, Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands.; Radboud Institute for Health Sciences (RIHS), Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands., Meulewaeter E; Department of Dermatology, Ghent University Hospital, Ghent, Belgium., Hakobjan M; Department of Human Genetics, Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands., Heddes N; Department of Dermatology, Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands., Traks T; Department of Dermatology, University of Tartu, Tartu, Estonia.; Department of Dermatology, Tartu University Hospital, Tartu, Estonia., Kingo K; Department of Dermatology, University of Tartu, Tartu, Estonia.; Department of Dermatology, Tartu University Hospital, Tartu, Estonia., Galluzzo M; Department of Dermatology, University of Rome Tor Vergata, Rome, Italy., Talamonti M; Department of Dermatology, University of Rome Tor Vergata, Rome, Italy., Lambert J; Department of Dermatology, Ghent University Hospital, Ghent, Belgium., Coenen MJH; Radboud Institute for Health Sciences (RIHS), Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands.; Department of Human Genetics, Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands., de Jong EMGJ; Department of Dermatology, Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands.; Radboud Institute for Health Sciences (RIHS), Radboud University Medical Centre (Radboudumc), Nijmegen, The Netherlands.; Radboud University, Nijmegen, The Netherlands.
المصدر: Journal of the European Academy of Dermatology and Venereology : JEADV [J Eur Acad Dermatol Venereol] 2020 Jan; Vol. 34 (1), pp. 112-118. Date of Electronic Publication: 2019 Aug 05.
نوع المنشور: Journal Article; Multicenter Study
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9216037 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-3083 (Electronic) Linking ISSN: 09269959 NLM ISO Abbreviation: J Eur Acad Dermatol Venereol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley-Blackwell
Original Publication: Amsterdam ; New York : Elsevier Science Publishers, c1992-
مواضيع طبية MeSH: Antibodies, Monoclonal, Humanized/*therapeutic use , Dermatologic Agents/*therapeutic use , Interleukin-17/*genetics , Psoriasis/*drug therapy , Psoriasis/*genetics, Adult ; Cohort Studies ; Europe ; Female ; Genetic Variation/genetics ; Humans ; Male ; Middle Aged ; Open Reading Frames/genetics ; Pharmacogenomic Testing ; Treatment Outcome ; Untranslated Regions/genetics
مستخلص: Background: Genetic predictors for treatment response could optimize allocation of biological treatment in patients with psoriasis. There is minimal knowledge about pharmacogenetics of anti-IL-17 agents.
Objectives: To assess whether genetic variants in the protein-coding region or untranslated regions of the IL-17A gene are associated with response to IL-17A inhibitors in patients with psoriasis.
Methods: This was a multicenter European cohort study investigating pharmacogenetics of IL-17A inhibitors in patients with psoriasis. Patients with plaque psoriasis treated with secukinumab or ixekizumab in daily practice were included. For all participants, the protein-coding region and untranslated regions of the IL-17A gene were analysed using Sanger sequencing. Identified genetic variants were tested for association with response to secukinumab/ixekizumab, measured as ∆PASI, after 12 weeks (primary outcome) and after 24 weeks (secondary outcome). Association was tested using a linear regression model with correction for baseline PASI as a fixed covariate and for biological naivety and body mass index as additional covariates.
Results: In total, 134 patients treated with secukinumab or ixekizumab were included. Genotyping of the cohort identified genetic variants present in untranslated regions and intronic DNA, but not in the protein-coding region of the IL-17A gene. Five genetic variants in non-coding DNA with a known or suspected functional effect on IL-17A expression were selected for association analyses: rs2275913, rs8193037, rs3819025, rs7747909 and rs3748067. After 12 weeks, 62% of patients achieved PASI75 and 39% achieved PASI90. At week 24, PASI75 and PASI90 response rates were 72% and 62%, respectively. No associations were found between the five genetic variants and ∆PASI, PASI75 or PASI90 after 12 and 24 weeks of anti-IL-17A treatment.
Conclusions: Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene. Pharmacogenetics of IL-17A inhibitors in the treatment of psoriasis requires further exploration.
(© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
التعليقات: Comment in: J Eur Acad Dermatol Venereol. 2020 Jan;34(1):11-12. (PMID: 31930644)
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معلومات مُعتمدة: National Psoriasis Foundation/USA
المشرفين على المادة: 0 (Antibodies, Monoclonal, Humanized)
0 (Dermatologic Agents)
0 (IL17A protein, human)
0 (Interleukin-17)
0 (Untranslated Regions)
BTY153760O (ixekizumab)
DLG4EML025 (secukinumab)
تواريخ الأحداث: Date Created: 20190710 Date Completed: 20201208 Latest Revision: 20201214
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7004147
DOI: 10.1111/jdv.15787
PMID: 31287604
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-3083
DOI:10.1111/jdv.15787