Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease

Clin Gastroenterol Hepatol. 2013 Apr;11(4):444-7. doi: 10.1016/j.cgh.2012.10.020. Epub 2012 Oct 24.

Abstract

There are few therapeutic options for patients with inflammatory bowel disease who lose response to infliximab because they produced antibodies against the drug. We performed a retrospective analysis to investigate whether administration of immune modulators to 5 patients who developed antibodies to infliximab (ATI) restored response to this drug; 3 patients were given azathioprine/6-mercaptopurine and 2 patients were given methotrexate. Concentrations of infliximab and ATIs, and antitumor necrosis factor (TNF) activity, were analyzed using enzyme-linked immunosorbent assay-based competition assays of serum samples collected before and after patients were given the immunomodulator. In all patients, levels of ATIs gradually decreased and trough levels of infliximab increased; clinical responses were restored to all patients. In competition assays, immunomodulator-induced elimination of ATIs was associated with increased anti-TNF activity in serum. The addition of immunomodulators to therapy might be helpful to patients who have lost response to anti-TNF agents owing to formation of antidrug antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology*
  • Azathioprine / administration & dosage
  • Drug Therapy, Combination / methods
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab
  • Male
  • Mercaptopurine / administration & dosage
  • Methotrexate / administration & dosage
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Mercaptopurine
  • Azathioprine
  • Methotrexate