Early detection of anti-drug antibodies during initiation of anti-tumour necrosis factor therapy predicts treatment discontinuation in inflammatory bowel disease

Aliment Pharmacol Ther. 2021 Jun;53(11):1190-1200. doi: 10.1111/apt.16333. Epub 2021 Apr 19.


Background: Anti-drug antibodies develop mostly during the induction therapy with anti-tumour necrosis factor (TNF) drugs and can be revealed by means of a drug-tolerant assay.

Aim: To investigate whether the early detection of anti-drug antibodies during the induction therapy was predictive of treatment discontinuation.

Methods: In a prospective study, consecutive patients with inflammatory bowel disease (IBD), who should start an anti-TNF, were enrolled and followed regularly during 24 months or less in case of non- or loss of response (LOR) or adverse events requiring treatment discontinuation. Anti-TNF levels and anti-drug antibodies were measured at week 2 for adalimumab (ADA) and weeks 2 and 6 for infliximab (IFX) using a drug-tolerant assay.

Results: One hundred and eight patients were enrolled (54 under ADA). At week 2, antibodies to ADA and to IFX were detected in 76% and 67% of patients. Time to treatment discontinuation was significantly shorter (P < 0.001) in patients with antibodies to ADA ≥2.0 µg/mL-eq (6.0 vs 24 months, HR = 18.51, 95% CI [4.35-78.71]) or with antibodies to IFX ≥4.0 µg/mL-eq (5.5 vs >24 months, HR = 13.89, 95% CI [4.08-47.31]) at week 2 compared to patients without positive antibodies. Antibodies to ADA and to IFX were predictive of treatment failure within 24 months with a sensitivity of 79% and 62%, and specificities and positive predictive values of 100%. In multivariate analysis, antibodies to ADA or to IFX at week 2 were the only factors associated with treatment discontinuation.

Conclusions: The prevalence of antibodies to anti-TNF is high when detected early using a drug-tolerant assay, and their appearance predicts further treatment discontinuation.

MeSH terms

  • Adalimumab / therapeutic use
  • Humans
  • Inflammatory Bowel Diseases* / diagnosis
  • Inflammatory Bowel Diseases* / drug therapy
  • Infliximab / therapeutic use
  • Prospective Studies
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha*


  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab