Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated With Infliximab

Inflamm Bowel Dis. 2020 Apr 11;26(5):756-763. doi: 10.1093/ibd/izz195.

Abstract

Background and aims: Inflammatory bowel diseases (IBDs) are treated with anti-TNF agents. Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Previous evidence suggests cleavage of infliximab (IFX) by Matrix Metalloproteinase 3 (MMP3) as a mechanism leading to loss of response. Our study aimed to evaluate if MMP3 serum levels could be considered an early marker of anti-TNF nonresponse and to analyze the correlation with other biochemical markers of treatment failure such as IFX trough levels and anti-IFX antibodies, inflammatory markers, and albumin levels.

Methods: Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks. Clinical and biochemical data (Harvey-Bradshaw index [HBI], Mayo score, body mass index [BMI], C-reactive protein [CRP], fecal calprotectin and albumin levels), MMP3 serum levels, and drug monitoring were assessed at baseline, postinduction, and 52 weeks.

Results: The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001). The MMP3 levels tended to be higher in patients without antidrug antibodies than in patients with antidrug antibodies at postinduction and 52 weeks.

Conclusions: The MMP3 serum determination may represent an early marker of response to infliximab.

Keywords: Metalloproteinase 3; TNF failure; inflammatory bowel disease; infliximab.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Albumins / analysis
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Drug Monitoring / methods
  • Feces / chemistry
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Induction Chemotherapy
  • Infliximab / therapeutic use*
  • Leukocyte L1 Antigen Complex / analysis
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies
  • Treatment Failure
  • Young Adult

Substances

  • Albumins
  • Biomarkers
  • Gastrointestinal Agents
  • Leukocyte L1 Antigen Complex
  • C-Reactive Protein
  • Infliximab
  • MMP3 protein, human
  • Matrix Metalloproteinase 3