The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual Participant Data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as (co)indication for start of anti-TNF therapy, >3 doses, and remission of luminal and pCD at anti-TNF discontinuation. Primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to retreatment and risk factors associated with relapse as assessed by Cox regression analysis.309 patients from 12 studies in 10 countries were included. Median duration of anti-TNF treatment was 14 months [IQR 5.8 - 32.5]. Most patients were treated for pCD without active luminal disease [89%], received first line anti-TNF therapy [87%] and continued immunomodulatory following anti-TNF discontinuation [78%]. Overall cumulative incidence of relapse was 36% [95% CI 25-48%] and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation. Risk factors for relapse included smoking [HR 1.5 (1.0, 2.1)] and history of proctitis [HR 1.7 (1.1, 2.5)]. Overall retreatment response rate was 82%.This IPD-MA, on predominantly patients with pCD without active luminal disease and first line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup
