Background Ustekinumab is a human monoclonal antibody that targets interleukin (IL)-12 and IL-23 and it is effective for the treatment of Crohn’s disease (CD). However, a group of patients will not respond or over time will experience loss of response (LOR) to ustekinumab. Evidence supporting the effectiveness of ustekinumab dose escalation for LOR is scarce. The aim of this study was to assess the effectiveness of ustekinumab dose escalation in a cohort of patients with active CD Methods Multicentric retrospective cohort study conducted in 5 tertiary Andalusian centers. Patients with active CD who received a standard-dose intravenous (IV) induction and at least one subcutaneous (SC) ustekinumab dose were included. All enrolled patients received dose escalation by either shortening the interval between the maintenance doses to every 4 or 6 weeks, IV reinduction or a combination of strategies. The primary outcome of the study was to assess corticosteroid (CS)-free clinical remission (HBI ≤4) at week 16. Secondary outcomes were CS-free clinical response (decrease of HBI ≥ 3 points from baseline) at week 16 and on the last follow-up, CS-free clinical remission on the last follow-up and ustekinumab persistence after dose escalation Results A total of 84 patients were included (54,8% female, median duration of CD 13,5 years). A 47,5% of the patients had history of previous abdominal surgery and 55% had been treated with 2 or more biologics. Patients were dose-escalated after a median treatment duration of 37 weeks (IQR 23–54). The most frequent type of dose escalation was the 90 mg every 4 weeks regimen (58%). A 25% of the patients were on concomitant immunomodulators at escalation. At week 16 from dose escalation the proportion of patients in CS-free response was 50/84 (59%) including 18/84 (21,4%) in CS-free remission. Follow-up data beyond week 20 were available for 61/84 patients (72.6%). On the last follow-up visit, 29/61 (47,5%) patients responded to treatment without concomitant CS of which 19/61 (31%) were in CS-free clinical remission. Systemic CS were discontinued in 21/44 (47.7%) patients who were on CS at the time of dose escalation. Ustekinumab was discontinued in 14/84 (17%) of the patients due to clinical non-response (ustekinumab persistence was 81% at 14 months of follow-up). Adverse events following dose escalation were reported in 4 of the 84 patients (7.7%), none of them were serious. Conclusion Dose escalation of ustekinumab maintenance was effective in over 50% of the patients and the treatment persistence was high. This strategy should be considered in patients who are not responsive or have LOR to ustekinumab on an 8-week dose maintenance interval

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