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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  PASI 75 and 39% achieved  PASI 90. At week 24,  PASI 75 and  PASI 90 response rates were 72% and 62%, respectively. No associations were found between the five genetic variants and ∆ PASI ,  PASI 75 or  PASI 90 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.

journal of the european academy of dermatology and venereology

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