Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis

Abstract

BACKGROUND: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. OBJECTIVES: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. METHODS: We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with >/= 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (PASI corrected for baseline PASI, primary analysis) and Pearson's chi2 -test or Fisher's exact test (PASI 75, secondary analysis). RESULTS: We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better PASI response to etanercept after 3 months (P = 0.025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (PASI) to ustekinumab (P = 0.017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (PASI) to ustekinumab (P = 0.031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis. CONCLUSIONS: We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.