The Polymorphism Rs763780 in the IL-17F Gene is Associated with Response to Biological Drugs in Patients with Psoriasis

Abstract

Psoriasis improves when IL-17 is blocked. Anti-TNF drugs reduce the IL-17 signaling pathway, and anti-IL-17 drugs are being developed to treat moderate-to-severe psoriasis. We analyzed three SNPs in IL-17A (rs2275913 and rs10484879) and IL-17F (rs763780) to look for an association with psoriasis and/or with response to anti-TNF drugs or ustekinumab. We included 197 healthy controls and 194 patients with moderate-to-severe psoriasis. The results of the univariate analysis showed an association between rs10484879 and psoriasis, although this relationship disappeared after adjustment for HLA-C (rs12191877). We also found an association between rs763780 (IL-17F) and response to ustekinumab (n = 70) and infliximab (n = 37) at 3 and 6 months and an association between rs763780 and the response to adalimumab at 6 months (n = 67).

Keywords::

• adalimumab
• etanercept
• IL-17
• infliximab
• pharmacogenetics
• psoriasis
• rs763780
• rs10484879
• rs2275913
• ustekinumab

Acknowledgements

The authors are grateful to T O’Boyle for editorial assistance and C Carazo for data collection. This study would not have been possible without the cooperation of controls and patients.

Financial & competing interests disclosure

This study was supported by Instituto de Salud Carlos III (FIS PI10/01740), Fundación Teófilo Hernando and AbbVie. R Prieto-Pérez holds a grant from Universidad Autónoma de Madrid (FPI program 2013). E Daudén has conflicts of interest (advisory board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking and research support) with the following pharmaceutical companies: AbbVie (Abbott), Amgen, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD and Celgene. F Abad-Santos has been a consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Farmalíder, Ferrer, GlaxoSmithKline, Janssen-Cilag, Kern, Normon, Servier, Teva and Zambon. P de la Cueva has conflicts of interest (advisory board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking and/or research support) with the following pharmaceutical companies: AbbVie (Abbott), Astellas, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD, Gebro, Isdin and Lilly. JL López Estebaranz has conflicts of interest (advisory board member, speaker or participation in clinical trials) with AbbVie, Amgen, Pfizer, MSD, Janssen-Cilag, Lilly, Celgene. O Baniandrés has conflicts of interest (participation in clinical trials and honoraria for speaking) with the following pharmaceutical companies: AbbVie (Abbott), Janssen-Cilag, Leo Pharma, Pfizer and MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by Instituto de Salud Carlos III (FIS PI10/01740), Fundación Teófilo Hernando and AbbVie. R Prieto-Pérez holds a grant from Universidad Autónoma de Madrid (FPI program 2013). E Daudén has conflicts of interest (advisory board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking and research support) with the following pharmaceutical companies: AbbVie (Abbott), Amgen, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD and Celgene. F Abad-Santos has been a consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Farmalíder, Ferrer, GlaxoSmithKline, Janssen-Cilag, Kern, Normon, Servier, Teva and Zambon. P de la Cueva has conflicts of interest (advisory board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking and/or research support) with the following pharmaceutical companies: AbbVie (Abbott), Astellas, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD, Gebro, Isdin and Lilly. JL López Estebaranz has conflicts of interest (advisory board member, speaker or participation in clinical trials) with AbbVie, Amgen, Pfizer, MSD, Janssen-Cilag, Lilly, Celgene. O Baniandrés has conflicts of interest (participation in clinical trials and honoraria for speaking) with the following pharmaceutical companies: AbbVie (Abbott), Janssen-Cilag, Leo Pharma, Pfizer and MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.