IL17RA gene variants and anti-TNF response among psoriasis patients

Abstract

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

“…[33][34][35][36][37][38][39][40][41][42][43] For all significant associations, except TLR9 (rs352139) and LY96 (rs11465996), similar tendencies were observed for ORs for each of the anti-TNF agents (data available on request). To our knowledge, this is one of the largest cohorts for evaluation of response in patients treated with ustekinumab 44,45 and the second largest for evaluation of anti-TNF; only a Canadian study (also involving treatment primarily for psoriatic arthritis) had more patients.…”

A systematic review of pharmacogenetic studies on the response to biologics in patients with psoriasis

“…The field of pharmacogenetics is growing rapidly. Already, new papers have been published following the end date of our literature search, discovering response‐associated polymorphisms in genes not described previously for psoriasis, such as CD84 , PGLYR4 , ZNF816A , CTNNA2 , MAP3K1 and HTR2A …”

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

“…In a study of 234 psoriasis patients, heterozygosity for rs6427528 (GA) SNP in the CD84 gene showed a better response to etanercept after 3 months compared to the homozygous reference group (GG) . One SNP in the promoter region of IL17RA (rs4819554) significantly influenced the response to anti‐TNF drugs (adalimumab, etanercept and infliximab) at week 12 . An association between IL17F (rs763780) and response to anti‐TNF drugs (infliximab and adalimumab) and ustekinumab have been reported .…”

“…161 One SNP in the promoter region of IL17RA (rs4819554) significantly influenced the response to anti-TNF drugs (adalimumab, etanercept and infliximab) at week 12. 162 An association between IL17F…”