Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation

EBioMedicine. 2017 Jul:21:123-130. doi: 10.1016/j.ebiom.2017.06.004. Epub 2017 Jun 7.

Abstract

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62μg/mL vs. 1.15μg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3μg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250μg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.

Keywords: Antibodies to infliximab; Fecal calprotectin; Therapeutic escalation; Ulcerative colitis.

Publication types

  • Multicenter Study

MeSH terms

  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies / blood
  • Antibodies / immunology*
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / metabolism*
  • Endoscopes
  • Female
  • Humans
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / pharmacokinetics
  • Immunologic Factors / therapeutic use
  • Infliximab / adverse effects*
  • Infliximab / pharmacokinetics
  • Infliximab / therapeutic use
  • Kaplan-Meier Estimate
  • Leukocyte L1 Antigen Complex / metabolism*
  • Male
  • Odds Ratio
  • Proportional Hazards Models

Substances

  • Anti-Inflammatory Agents
  • Antibodies
  • Immunologic Factors
  • Leukocyte L1 Antigen Complex
  • Infliximab