Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa

Dermatology. 2023;239(5):746-752. doi: 10.1159/000531558. Epub 2023 Jun 16.

Abstract

Background: Results of randomized clinical trials show great variation in response to treatment with adalimumab (ADA) in hidradenitis suppurativa (HS). This varied response may be associated with genetic polymorphisms.

Objectives: The aim of the study was to study the association between carriage of single nucleotide polymorphisms (SNPs) in the promoter of the tumor necrosis factor (TNF) gene and their response to ADA.

Methods: Patients with moderate to severe HS who received ADA treatment for at least 12 weeks were enrolled. SNPs were analyzed with PCR-restriction fragment length polymorphism. Hidradenitis Suppurativa Clinical Response (HiSCR) score, International Hidradenitis Suppurativa Severity Scoring System 4 (IHS4) score, inflammatory lesion (AN) count, and draining tunnel (dT) count were collected at weeks 0, 12, 24, 36, and 48.

Results: HiSCR response after 12 weeks of ADA treatment was 71.8% among carriers of the common GGG haplotype and 50.0% among carriers of minor frequency SNP haplotypes (p: 0.031; odds ratio: 0.39). This significant difference persisted until week 36. Carriers of minor frequency SNP haplotypes also had a lower relative decrease of the AN count at weeks 12 and 24; the dT count and IHS4 were not statistically different between the two groups.

Conclusions: Carriage of at least one minor frequency SNP haplotype of the promoter of the TNF gene is associated with a decreased response to ADA. This association may have an impact on treatment decision-making.

Keywords: Adalimumab; Hidradenitis suppurativa; Single nucleotide polymorphisms; Treatment response.

MeSH terms

  • Adalimumab / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use
  • Hidradenitis Suppurativa* / complications
  • Hidradenitis Suppurativa* / drug therapy
  • Hidradenitis Suppurativa* / genetics
  • Humans
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha* / genetics

Substances

  • Adalimumab
  • Anti-Inflammatory Agents
  • TNF protein, human
  • Tumor Necrosis Factor-alpha