BACKGROUND: Antitumor necrosis factor (TNF) dose escalation is performed to improve therapeutic response and optimize outcomes in patients with Crohn's disease (CD). We aimed to describe the durability of anti-TNF therapy in patients with CD receiving escalated anti-TNF therapy, along with the overall durability of anti-TNF treatment between patients managed with a proactive versus reactive therapeutic drug monitoring (TDM) approach. METHODS: We undertook a retrospective multicentre cohort study. One center practiced proactive TDM with a weekly virtual TDM clinic, while the other practiced reactive TDM. Patients receiving escalated infliximab or adalimumab therapy for CD from January 2015 to April 2022 were included. Durability was defined as the time from biologic start to cessation for treatment failure. RESULTS: About 239 patients (45% female, median age 39) meeting criteria for inclusion were identified. About 165 patients were included in the proactive TDM cohort and 74 in the reactive TDM cohort.Anti-TNF naive patients had significantly higher durability of therapy when compared with the anti-TNF exposed patients for both overall durability (P = .045) and durability postescalation (P = .017). The proactive TDM cohort had significantly higher durability when compared with the reactive cohort for both overall durability (P = .001) and durability postescalation (P = .002). CONCLUSIONS: This multicentre, retrospective cohort study illustrates the importance of dose escalation as a therapeutic strategy in IBD care. The durability of anti-TNF therapy is superior in anti-TNF naive compared to exposed patients and can be improved further by proactive TDM to guide dose optimization.