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

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin12/13 (111 2/2( L12/kinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IUB (rsl L1B3623,rsl 1436271 LY96 (rsl 1465996, TLR2 (rsl 193(221 rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IUB (rslIL1436231rsl 1436271 TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q < 0.20). The results suggest that genetic variants related to increased IL-1 p level beta say be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-y levels gamma may be favorable when treating psoriasis with ustekinumab.