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

Abstract

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.

• Authors: Quentin Tournier, Stephane Paul, Nicolas Williet, Anne-Emmanuelle Berger, Pauline Veyrard, Gilles Boschetti, Bertrand Le Roy, Martin Killian, Jean Marc Phelip, Bernard Flourie, Stephane Nancey, Xavier Roblin
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 53 Issue 11 Pg. 1190-1200 (06 2021) ISSN: 1365-2036 [Electronic] England
• PMID: 33872404 (Publication Type: Journal Article)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab

Topics

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