P702 Long term outcomes following de-escalation of dose-intensified ustekinumab in patients with Crohn’s disease

Abstract

Abstract Background Data on outcomes following de-escalation of dose-intensified ustekinumab (UST) in Crohn’s disease (CD) have not been reported. This retrospective cohort study aimed to evaluate the failure rates 6, 12, and 24 months after de-escalation from dose-intensified UST to standard dose UST and identify predictors of failure. Methods Single centre, retrospective study of consecutive CD patients undergoing de-escalation of dose-intensified UST (90mg 4-weekly) to standard dosing (90mg 8-weekly). De-escalation and post de-escalation decisions were informed by protocolised 6-monthly assessment using Harvey-Bradshaw Index, C-reactive protein (CRP), faecal calprotectin (FCP), drug level and intestinal ultrasound. Failure was defined by re-escalation of UST, corticosteroids, switch out of class, or IBD-related hospitalisation or surgery. Success was defined by continued standard UST dosing. Categorical variables were compared using Fisher-exact and continuous variables using Mann-Whitney U tests between groups. Results 14 patients underwent de-escalation from April 2020 to March 2023. The median age was 41 years, disease duration 15 years, and duration on dose-intensified UST 34 months. 43% received IV reinduction at time of escalation, 86% had previous exposure to advanced therapies, of which 43% were dose-intensified. 36% were on an immunomodulator (IMM) at de-escalation. In the 6 months prior to de-escalation, the median CRP was 3.5mg/L, FCP 96mg/g, and 91% were in sonographic remission. 5/14 (36%) failed de-escalation at 6 months and 9/14 (64%) failed by 12 months. Of those with 24 months follow up, 9/12 (75%) failed de-escalation. Median time to failure was 8 months (IQR 4.5-13). All patients who failed underwent re-escalation and 2 required surgery. UST drug levels reduced from 3.6 to 1.9mg/mL 6 months post de-escalation. Re-escalation successfully recaptured response in 7/9 (78%). A greater proportion of patients with successful de-escalation at 12 months received concomitant IMM compared to those that failed (80% vs. 11%, respectively; p = 0.02). There were no other significant differences in clinical or disease characteristics between those with failure vs. success at 6, 12, or 24 months, although numbers were small (Table 1). Conclusion One-third of patients failed de-escalation of dose-intensified UST at 6 months, two-thirds failed at 12 months and three-quarters by 24 months. Patients considered for a trial of de-escalation need close, objective monitoring as most failure occurs early, and re-escalation is successful in the majority. Concomitant IMM may reduce failure rates and should be considered. Further studies are required to confirm these findings and identify additional predictors of de-escalation failure.