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

Br J Dermatol. 2018 Jan;178(1):86-94. doi: 10.1111/bjd.15753. Epub 2017 Dec 14.

Abstract

Background: Biologics are indicated for treating moderate-to-severe psoriasis. As the number of biologics registered for the treatment of psoriasis increases, so does the need for biomarkers to guide personalized therapeutic decisions. Genetic variants might serve as predictors for treatment response, a field of research known as pharmacogenetics.

Objectives: To assess which genetic variants are associated with response to biologics in patients with psoriasis according to current literature.

Methods: A systematic search was performed in Embase, MEDLINE, the Cochrane Library and Web of Science. In total, 26 papers were included in this systematic review; 24 original studies and two meta-analyses. Quality was assessed using a predesigned form and risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related to the therapeutic target or to psoriasis susceptibility. Studied populations were small and results were divergent, especially for studies investigating tumour necrosis factor inhibitors. The evidence for the role of HLA-Cw6 in ustekinumab efficacy shows minimal heterogeneity, with a higher response rate among patients who were positive for HLA-Cw6 reported across three of five studies.

Conclusions: Pharmacogenetic studies in psoriasis have generated divergent results. Replication of findings in larger cohorts is required. Large-scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of outcomes for treatment with biologics.

Publication types

  • Systematic Review

MeSH terms

  • Adalimumab / therapeutic use
  • Biological Products / therapeutic use*
  • Cohort Studies
  • Dermatologic Agents / therapeutic use*
  • Etanercept / therapeutic use
  • Genome-Wide Association Study
  • Humans
  • Infliximab / therapeutic use
  • Meta-Analysis as Topic
  • Pharmacogenomic Testing
  • Polymorphism, Genetic
  • Psoriasis / drug therapy*
  • Psoriasis / genetics
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics
  • Ustekinumab / therapeutic use

Substances

  • Biological Products
  • Dermatologic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Ustekinumab
  • Adalimumab
  • Etanercept