Response to IL17A inhibitors for psoriasis multicentre study

[Fred]

This study aimed to assess whether genetic variants in the protein‐coding region or untranslated regions of the IL17A gene are associated with response to IL17A inhibitors in patients with psoriasis.

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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‐IL17 agents.

Objectives:
To assess whether genetic variants in the protein‐coding region or untranslated regions of the IL17A gene are associated with response to IL17A inhibitors in patients with psoriasis.

Methods:
This was a multicenter European cohort study investigating pharmacogenetics of IL17A 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 IL17A gene were analyzed 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 IL17A gene. Five genetic variants in non‐coding DNA with a known or suspected functional effect on IL17A expression were selected for association analyses: rs2275913, rs8193037, rs3819025, rs7747909, 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‐IL17A treatment.

Conclusions:
Response to IL17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein‐coding and untranslated regions of the IL17A gene. Pharmacogenetics of IL17A inhibitors in the treatment of psoriasis requires further exploration.

Source: onlinelibrary.wiley.com

*Early view funding unknown

Cosentyx (secukinumab)

Taltz (ixekizumab)