Factors predicting the therapeutic response to infliximab during maintenance therapy in Japanese patients with Crohn's disease

PLoS One. 2018 Oct 4;13(10):e0204632. doi: 10.1371/journal.pone.0204632. eCollection 2018.

Abstract

Since anti-tumor necrosis factor (TNF)-α agents (TNF-α inhibitors) induce both clinical response and remission in patients with moderate to severe inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally changed the approach to treatment for patients with IBD. Infliximab (IFX) is a TNF-α inhibitor approved for the induction and remission of Crohn's disease (CD). However, even among patients who initially demonstrate a clinical response to IFX therapy, secondary loss of response occurs, although the reason remains unknown. We therefore investigated predictive factors associated with the response to IFX in long-term maintenance treatment in Japanese CD patients. Eight types of single-nucleotide polymorphisms (SNPs) were investigated using the real-time PCR method, and patient characteristics were collected from the electronic medical records. The Crohn's Disease Activity Index criteria were used as the response to IFX therapy. The observation period was 1 year after IFX had been administered for more than 1 year. Associations between the IFX response and patient characteristics were evaluated using the multivariate logistic regression model. We studied 121 unrelated adult Japanese with CD treated for more than 1 year with IFX as outpatients at Keio University Hospital from November 1, 2014 to November 30, 2015. Among them, 71 were classified as in remisson. In multivariate analysis, patients with the TNF-α 857C>T C/C genotype, shorter disease duration, without double dosing, and combination treatment with an immunomodulator had higher remisson rates than those with the C/T or T/T genotype, longer disease duration, with double dosing, and no combination treatment with an immunomodulator. The response to IFX in Japanese CD patients may therefore be predicted by these 4 characteristics in actual clinical practice.

MeSH terms

  • Adult
  • Asian Continental Ancestry Group
  • Crohn Disease / drug therapy*
  • Crohn Disease / genetics
  • Drug Therapy, Combination / methods
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Genotype
  • Humans
  • Immunologic Factors
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics
  • Infliximab / therapeutic use*
  • Logistic Models
  • Male
  • Polymorphism, Single Nucleotide / drug effects
  • Polymorphism, Single Nucleotide / genetics
  • Remission Induction / methods
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Gastrointestinal Agents
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • Infliximab

Grant support

The authors received no specific funding for this work.