Genetic prediction of the effectiveness of biologics for psoriasis treatment

Abstract

Anti-tumor necrosis factor (TNF)-α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome-wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti-TNF-α therapy using Human Omni Express-8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti-TNF-α agents (strongest effect, P < 7.11E-06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti-TNF-α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF-α production, was previously reported to be associated with treatment responses to TNF-α inhibitors.

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.…”

Alteration of serum thymus and activation‐regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti‐interleukin‐17A agents

“…At present, several biomarkers reflecting severity/activity of psoriasis and response to biologic therapy have been proposed. These biomarkers include genotypes of human leukocyte antigen, cytokine‐related genes and inflammation signal‐related genes, miRNA, serum proteins, such as C‐reactive protein, and cytokine‐related inflammation and leucine‐rich α2‐glycoprotein . Among them, neutrophil : lymphocyte ratio can be easily and regularly measured in daily clinical examination .…”

Challenges of biological therapy in patients with pustular psoriasis coexisting with psoriatic arthritis

“…Prowadzone są także badania, które mają udowodnić, że odpowiedź na leczenie może mieć podło-że genetyczne [36][37][38][39][40]. Jest ono związane z polimorfizmami genu TNF, receptora TNF-1B (TNFR1B) oraz genu TNFAIB3, jak również z polimorfizmami innych genów.…”

“…Studies are also conducted in order to verify whether response to treatment may be genetically conditioned [36][37][38][39][40]. It is associated with polymorphisms of the TNF gene, TNF receptor 1B (TNFR1B) and TNFAIB3 gene, as well as polymorphisms of other genes.…”