Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy

Clin Gastroenterol Hepatol. 2014 Sep;12(9):1474-81.e2; quiz e91. doi: 10.1016/j.cgh.2014.01.033. Epub 2014 Jan 29.


Background & aims: Few agents are available for the treatment of inflammatory bowel diseases, and patients frequently become unresponsive to biologics. We investigated the feasibility of reinitiating infliximab therapy for patients who previously received only episodic therapy with, lost response to, or had infusion reactions to infliximab. We also aimed to identify factors associated with the success and safety of restarting infliximab, such as antibodies to infliximab and trough levels of the drug.

Methods: From the inflammatory bowel disease biobank, we identified 128 consecutive patients (105 patients with Crohn's disease, 23 patients with ulcerative colitis) who restarted infliximab after a median 15-month discontinuation (range, 6-125 mo; 28 patients for loss of response or infusion reactions, 100 patients for remission or pregnancy). We also analyzed serum samples that had been collected during the first period of infliximab therapy (T-1), when therapy was reinitiated (T0), and at later time points (T+1, T+2) for trough levels and antibodies to infliximab. We investigated correlations among response to treatment, infusion reactions, treatment modalities, trough levels, and antibodies to infliximab.

Results: Reinitiation of infliximab therapy produced a response in 84.5% of patients at week 14, 70% of patients at 1 year, and in 61% of patients at more than 4 years. Fifteen patients had acute infusion reactions and 10 patients had delayed infusion reactions. The absence of antibodies to infliximab at T+1 (hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.026-0.74; P = .021) and reinitiation with concomitant immunomodulator therapy were associated with short-term responses (HR, 6.0; 95% CI, 1.3-27; P = .019). Pregnancy or remission as reason for discontinuation (HR, 2.70; 95% CI, 1.09-6.67; P = .033) and higher trough levels at T+1 (HR, 2.94; 95% CI, 1.18-7.69; P = .021) were associated with long-term response. Undetectable antibodies to infliximab at T+1 were associated with the safety of reinitiating therapy (HR for infusion reaction with detectable antibodies to infliximab, 7.7; 95% CI, 1.88-31.3; P = .004).

Conclusions: Reinitiating infliximab therapy can be safe and effective for patients with Crohn's disease or ulcerative colitis after a median 15-month discontinuation period.

Keywords: Antidrug Antibody; Drug Holiday; Pharmacokinetics; Remicade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies / blood*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / pharmacology
  • Female
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / immunology*
  • Immunologic Factors / pharmacokinetics*
  • Immunologic Factors / pharmacology
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab
  • Male
  • Middle Aged
  • Pregnancy
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antibodies
  • Antibodies, Monoclonal
  • Immunologic Factors
  • Infliximab