J M P A van den Reek1, M J H Coenen2, M van de L'Isle Arias1, J Zweegers1, D Rodijk-Olthuis1, J Schalkwijk1, S H Vermeulen3, I Joosten4, P C M van de Kerkhof1, M M B Seyger1, P L J M Zeeuwen1, E M G J de Jong1. 1. Department of Dermatology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands. 2. Department of Human Genetics, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands. 3. Department of Health Evidence, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands. 4. Department of Immunology, Radboud University Medical Center, Radboud Institutes for Molecular Life Sciences (RIMLS) and Health Sciences (RIHS), Nijmegen, the Netherlands.
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.
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.
Authors: N D Loft; L Skov; L Iversen; R Gniadecki; T N Dam; I Brandslund; H J Hoffmann; M R Andersen; R B Dessau; A C Bergmann; N M Andersen; P S Andersen; S Bank; U Vogel; V Andersen Journal: Pharmacogenomics J Date: 2017-07-11 Impact factor: 3.550
Authors: Cristina Membrive Jiménez; Cristina Pérez Ramírez; Almudena Sánchez Martín; Sayleth Vieira Maroun; Salvador Antonio Arias Santiago; María Del Carmen Ramírez Tortosa; Alberto Jiménez Morales Journal: J Pers Med Date: 2021-04-12
Authors: L V Putlyaeva; A M Schwartz; A V Klepikova; I E Vorontsov; I V Kulakovskiy; D V Kuprash Journal: Acta Naturae Date: 2017 Jul-Sep Impact factor: 1.845