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.
J Eur Acad Dermatol Venereol
; 34(1): 112-118, 2020 Jan.
Article
em En
| MEDLINE
| ID: mdl-31287604
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Interleucina-17
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Fármacos Dermatológicos
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Anticorpos Monoclonais Humanizados
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article