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Polymorphisms in CD 84 , IL 12B and TNFAIP 3 are associated with response to biologics in patients with psoriasis
Author(s) -
Reek J.M.P.A.,
Coenen M.J.H.,
L'Isle Arias M.,
Zweegers J.,
RodijkOlthuis D.,
Schalkwijk J.,
Vermeulen S.H.,
Joosten I.,
Kerkhof P.C.M.,
Seyger M.M.B.,
Zeeuwen P.L.J.M.,
Jong E.M.G.J.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15005
Subject(s) - ustekinumab , psoriasis area and severity index , medicine , etanercept , psoriasis , adalimumab , single nucleotide polymorphism , gastroenterology , immunology , genotype , disease , genetics , biology , tumor necrosis factor alpha , gene
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 LCE 3B and LCE 3C genes, and eight single‐nucleotide polymorphisms ( SNP s) in HLA‐C*06 , CD 84 , IL 12B , IL 23R , TRAF 3 IP 2 , ERAP 1 , IFIH 1 and TNFAIP 3 . 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 CD 84 (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 IL 12B variant showed a better response (∆ PASI ) to ustekinumab ( P  =   0·017) than the reference group ( CC ). Patients homozygous ( GG ) for the SNP in TNFAIP 3 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 CD 84 , a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.

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