부산대학교 도서관

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 < 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. [ABSTRACT FROM AUTHOR]