Influence of combination therapy with immune modulators on anti-TNF trough levels and antibodies in patients with IBD

Inflamm Bowel Dis. 2014 Dec;20(12):2292-8. doi: 10.1097/MIB.0000000000000208.


Background: It is important to identify factors that can reduce the incidence of immunogenicity against anti-tumor necrosis factor medication in patients with inflammatory bowel disease. The objective of our study was to evaluate the influence of cotreatment with immune modulators (IMs) on trough levels (TLs) and antidrug antibodies.

Methods: The records of all patients with inflammatory bowel disease at the Leiden University Medical Center who received either adalimumab or infliximab (IFX) in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated about the assessment of TL and antibodies and use of IM.

Results: Two hundred seventeen patients were included (108 patients IFX; 109 patients adalimumab). Mean TL in the IFX group was higher in the combination therapy group compared with the monotherapy group, 4.6 versus 7.5 µg/mL, P = 0.04. In the adalimumab group, the difference was not significant. In patients with IFX monotherapy, the incidence of antibody formation was higher compared with patients with combination therapy (29.8% versus 5.7%, P = 0.001). IFX patients with a suboptimal dose of IM had a higher TL compared with patients who had an optimal dose, P = 0.02. The incidence of antibody formation was lower in IFX patients who immediately started with IMs compared with patients who did not (33.3% versus 66.7%, P = 0.04).

Conclusions: The influence of combination therapy with IM on TL and antibodies to anti-tumor necrosis factor medication was significant for IFX-treated patients. Patients who started combination therapy immediately developed antibodies less often than patients who started later with concomitant medication.

MeSH terms

  • Adalimumab
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / blood
  • Anti-Inflammatory Agents / immunology
  • Antibodies / blood*
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibody Formation / drug effects*
  • Antibody Formation / immunology
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / blood
  • Gastrointestinal Agents / immunology
  • Humans
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology*
  • Infliximab
  • Male
  • Prognosis
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology*


  • Anti-Inflammatory Agents
  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab