Background: Inflammatory bowel disease (IBD) is often managed with anti-tumour necrosis factor-therapy (anti--TNFa), but treatment efficacy is compromised by high annual rates of loss of response (13%-21% per patient-year).

Aims: To assess whether the incidence of loss of response decreases with longer treatment duration

Methods: This was a multicentre, retrospective cohort study of patients with ulcerative colitis (UC) or Crohn's disease (CD) who received anti-TNFa for at least 4 months between 2011 and 2019. We studied the incidence of loss of response as a function of treatment duration, employing parametric survival modelling. Predictors of loss of response were identified by Cox regression analysis. Secondary outcomes included overall anti-TNFa discontinuation and dose escalation.

Results: We included 844 anti-TNFa treatment episodes in 708 individuals. Loss of response occurred in 211 (25.0%) episodes, with anti-drug antibodies detected in 66 (31.3%). During the first year, the incidence of loss of response was three-fold higher than after four years of treatment (17.2% vs 4.8% per patient-year, P<0.001). The incidence of anti-TNFa discontinuation (28.6% vs 14.0% per patient-year, P<0.001)and dose escalations (38.0% vs 6.8% per patient-year, P<0.001) also decreased significantly from the first year to after four years, respectively. Predictors of loss of response included UC (vs CD, adjusted hazard ratio [aHR] 1.53, 95% CI 1.10-2.15) and, among patients with CD, stricturing or penetrating disease (aHR 1.68, 95% CI 1.15-2.46) and male sex (aHR 0.55, 95% CI 0.38-0.78).
Immunomodulators were protective against loss of response with anti-drug antibodies (aHR 0.42, 95% CI 0.24-0.74).

Conclusions: Patients with sustained benefit to anti-TNFa after 2 years are at low risk of subsequent loss of response.