This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.
Psoriasis improves when IL-17 is blocked. Anti-TNF drugs reduce the IL-17 signaling pathway, and anti-IL-17 drugs are being developed to treat moderate-to-severe psoriasis. We analyzed three SNPs in IL-17A (rs2275913 and rs10484879) and IL-17F (rs763780) to look for an association with psoriasis and/or with response to anti-TNF drugs or ustekinumab. We included 197 healthy controls and 194 patients with moderate-to-severe psoriasis. The results of the univariate analysis showed an association between rs10484879 and psoriasis, although this relationship disappeared after adjustment for HLA-C (rs12191877). We also found an association between rs763780 (IL-17F) and response to ustekinumab (n = 70) and infliximab (n = 37) at 3 and 6 months and an association between rs763780 and the response to adalimumab at 6 months (n = 67).
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.
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases that affect both children and adults with a prevalence of 30% and 10%, respectively. Even though most of patients respond satisfactory to topical anti-inflammatory drugs, about 10% require one or more systemic treatments to achieve good control of their illness. The progressive and increasingly detailed knowledge in the immunopathogenesis of AD has allowed research on new therapeutic targets with very promising results in the field of biological therapy. In this article, we will review the different biological treatments with a focus on novel drugs. Their mechanism of action, current status and results from clinical trials and observational studies will be specified.
The adjusted results (false discovery rate) showed an association between five SNPs in TNFRSF1A, HTR2A, NFKBIA, ADAM33 and IL13 genes, and poor response to ustekinumab. Furthermore, six SNPs in CHUK, C17orf51, ZNF816A, STAT4, SLC22A4 and Corf72 genes were associated with better response to ustekinumab. However, there was no significant association between response to ustekinumab and SNPs in HLA-C as it has been recently described. Finally, a higher weight was obtained in nonresponders than responders (p = 0.018). Further studies would be necessary to be closer to personalized medicine.
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