The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study

Br J Dermatol. 2013 Oct;169(4):819-29. doi: 10.1111/bjd.12425.

Abstract

Background: Antitumour necrosis factor (anti-TNF)-α agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents.

Objectives: To study the association of single nucleotide polymorphisms (SNPs) of the TNF-α promoter and IL12B/IL23R genes with the response to anti-TNF-α in patients with psoriasis.

Methods: SNPs for the TNF-α promoter and IL12B/IL23R genes, and the presence of the HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)].

Results: Patients with the TNF-α-238GG genotype more frequently achieved a PASI75 at 6 months (82·5% vs. 58·8%, P = 0·049). At 6 months, patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI score and BSA (83·1% vs. 92·7%, P = 0·004; 82·7% vs. 92·6%, P = 0·009) and more frequently achieved PASI75 (71·4% vs. 96·3%, P = 0·006). More patients with the TNF-α-1031TT genotype achieved PASI75 at 3 months (90·8 vs. 75·7, P = 0·047) and 6 months (85·5% vs. 65·7%, P = 0·038) and demonstrated superior improvements in PASI at 6 months (89·9% vs. 78·7%, P = 0·041). Patients with the IL23R-GG genotype (rs11209026) achieved PASI90 at 6 months more frequently (66·3% vs. 0, P = 0·006) and the improvement of the PASI score was also greater (86·8% vs. 67·8%, P = 0·013). Patients with the HLA-Cw6 haplotype showed poorer response than those without this haplotype.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Case-Control Studies
  • Dermatologic Agents / therapeutic use
  • Etanercept
  • Female
  • Genotype
  • Humans
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin-12 / genetics*
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Dermatologic Agents
  • IL12RB1 protein, human
  • IL23R protein, human
  • Immunoglobulin G
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept