Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis. (1st May 2017)

• Record Type: Journal Article
• Authors: van den Reek, J.M.P.A.; Coenen, M.J.H.; van de L'Isle Arias, M.; Zweegers, J.; Rodijk‐Olthuis, D.; Schalkwijk, J.; Vermeulen, S.H.; Joosten, I.; van de Kerkhof, P.C.M.; Seyger, M.M.B.; Zeeuwen, P.L.J.M.; de Jong, E.M.G.J.
• Is Part Of: British journal of dermatology. Volume 176:Number 5(2017)
• Page Start: 1288
• Page End: 1296
• Publication Date: 2017-05-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.15005
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: 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 χ 2 ‐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.