P299 Loss-of-response to anti-tumour necrosis factor-α critically depends on treatment duration in patients with Inflammatory Bowel Disease. (27th May 2021)

• Record Type: Journal Article
• Authors: Schultheiss, J; Mahmoud, R; Louwers, J; van der Kaaij, M; van Hellemondt, B; van Boeckel, P; Mahmmod, N; Jharap, B; Fidder, H; Oldenburg, B
• Is Part Of: Journal of Crohn's and colitis. Volume 15(2021)Supplement 1
• Page Start: S327
• Page End: S328
• Publication Date: 2021-05-27
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjab076.423
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Inflammatory bowel disease (IBD) is often managed with anti-tumour necrosis factor-α (anti-TNFα) compounds, but only few studies have reported on long-term outcomes. We aimed to determine whether the incidence of loss-of-response decreases with longer treatment duration. Methods: In a multicentre, retrospective cohort study of patients with IBD who received anti-TNFα for at least 4 months between 2011-2019, we compared incidence rates of loss-of-response between different intervals of treatment duration and performed parametric survival modelling to assess changes with longer treatment duration. Cox regression analysis was performed to identify predictors of loss-of-response. Secondary outcomes included overall anti-TNFα discontinuation and dose escalation. Results: We included 900 anti-TNFα treatment episodes in 746 individual patients, with up to 9 years of follow-up. During follow-up, the most frequently observed reason for anti-TNFα discontinuation was loss-of-response (Figure 1), which occurred in 231 (25.7%) episodes, with presence of anti-drug antibodies in 67/231 (29%). Within the first year, the incidence of loss-of-response was threefold higher than after four years of treatment (17.3% versus 4.7% per patient-year, p<0.001). The incidence of overall drug discontinuation (28.6% versus 14.0% per patient-year, p<0.001) and dose escalations (36.5% versus 6.4% per patient-year, p<0.001) also decreased significantly from the first year to after four years, respectively. Risk factors for loss-of-response included stricturing or penetrating Crohn's disease (adjusted hazard ratio [aHR] 1.67, 95% CI 1.14 – 2.44), while male sex (aHR 0.74, 95% CI 0.56 – 0.98) and concomitant immunomodulators (aHR 0.73, 95% CI 0.54 – 0.98) were protective. Conclusion: Long-term use of anti-TNFα maintenance treatment is associated with a reduced risk of loss-of-response in patients with IBD.