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

BackgroundThe effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. ObjectivesWe aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. MethodsWe 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 (2)-test or Fisher's exact test (PASI 75, secondary analysis). ResultsWe included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better PASI response to etanercept after 3months (P=0025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (PASI) to ustekinumab (P=0017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (PASI) to ustekinumab (P=0031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis. ConclusionsWe 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.