New polymorphisms associated with response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis

Abstract

Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20-30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

“…[33][34][35][36][37][38][39][40][41][42][43] For all significant associations, except TLR9 (rs352139) and LY96 (rs11465996), similar tendencies were observed for ORs for each of the anti-TNF agents (data available on request). To our knowledge, this is one of the largest cohorts for evaluation of response in patients treated with ustekinumab 44,45 and the second largest for evaluation of anti-TNF; only a Canadian study (also involving treatment primarily for psoriatic arthritis) had more patients.…”

A systematic review of pharmacogenetic studies on the response to biologics in patients with psoriasis

“…The field of pharmacogenetics is growing rapidly. Already, new papers have been published following the end date of our literature search, discovering response‐associated polymorphisms in genes not described previously for psoriasis, such as CD84 , PGLYR4 , ZNF816A , CTNNA2 , MAP3K1 and HTR2A …”

SnapshotDx Quiz: February 2019

“…The SNP þ489 A/ A genotype was associated with a response to adalimumab in patients with psoriatic arthritis (Murdaca et al, 2014). Recently, investigators found an association of six SNPs involved in immune response, keratinocyte differentiation, and response to anti-TNF therapies for patients with moderate to severe plaque psoriasis (Prieto-Pérez et al, 2016). On the other hand, one study found that SNP data did not meaningfully contribute to the prediction of treatment response in patients with rheumatoid arthritis taking anti-TNFs (Sieberts et al, 2016).…”