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

Summary 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 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. Antibodies to adalimumab (ATA) or to infliximab (ATI) appeared early, during the induction therapy. Using the drug‐tolerant assay, we also identified the optimal thresholds for ATA and ATI associated with clinical relapse. Our findings highlight the critical contribution of using a drug‐tolerant assay and the usefulness to monitor early anti‐drug antibodies during the initiation of anti‐TNF therapy in IBD patients.