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

J. M.P.A. van den Reek*, M. J.H. Coenen, M. van de L'Isle Arias, J. Zweegers, D. Rodijk-Olthuis, J. Schalkwijk, S. H. Vermeulen, I. Joosten, P. C.M. van de Kerkhof, M. M.B. Seyger, P. L.J.M. Zeeuwen, E. M.G.J. de Jong

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 χ2-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.

Original languageEnglish
Pages (from-to)1288-1296
Number of pages9
JournalBritish Journal of Dermatology
Volume176
Issue number5
DOIs
Publication statusPublished - 1 May 2017
Externally publishedYes

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