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P299 Loss-of-response to anti-tumour necrosis factor-α critically depends on treatment duration in patients with Inflammatory Bowel Disease

Schultheiss, J.(1);Mahmoud, R.(1);Louwers, J.(1);van der Kaaij, M.(1);van Hellemondt, B.(1);van Boeckel, P.(2);Mahmmod, N.(2);Jharap, B.(3);Fidder, H.(1);Oldenburg, B.(1);

(1)University Medical Centre Utrecht, Division of Internal Medicine and Dermatology- Department of Gastroenterology and Hepatology, Utrecht, The Netherlands;(2)St. Antonius Hospital, Division of Internal Medicine- Department of Gastroenterology and Hepatology, Nieuwegein, The Netherlands;(3)Meander Medical Centre, Division of Internal Medicine- Department of Gastroenterology and Hepatology, Amersfoort, The Netherlands

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.Figure 1. Anti-TNF discontinuation with corresponding reasons

Conclusion

Long-term use of anti-TNFα maintenance treatment is associated with a reduced risk of loss-of-response in patients with IBD.

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