26 USTEKINUMAB DOSE ESCALATION EFFECTIVE IN REAL-WORLD USE FOR LUMINAL AND PERIANAL CROHN’S DISEASE

Abstract

Abstract Introduction Ustekinumab (UST) is effective for induction and maintenance of remission in Crohn’s disease (CD) as demonstrated in the UNITI trials. There is paucity of data in real world experience for dose escalation with UST, particularly for perianal disease. This study examines the effectiveness and safety of dose escalation in both luminal and perianal CD at a tertiary IBD referral center. Methods A retrospective, single center cohort study was conducted at the University of Texas Southwestern Medical Center examining outcomes of UST dose escalation in CD. Dose escalation was defined as increasing frequency to every four or six weeks. The primary outcomes were improvement in perianal disease as documented by the treating clinician and a composite outcome reflecting disease response. Patients who met the composite outcome had at least one of the following: steroid-free clinical response, objective improvement in disease activity on follow up CT, MRI or endoscopy, or normalization of CRP. Secondary outcomes included IBD-related surgery and adverse events. Patients were followed up to 6 months after dose intensification. Results 38 patients underwent dose intensification. 28 patients (74%) were escalated to every 4 week dosing and 10 patients (26%) were escalated to every 6 weeks. Baseline characteristics were recorded (see Table 1). 18/38 (48%) were escalated for primary non-response. Median time from UST induction to dose escalation was 10 months (IQR 2–24 months). Following escalation, patients were followed for a medianof 4.5 months (range 1–6 months). Nearly all (92%) patients had prior exposure to anti-TNF therapies and 74% had prior exposure to an anti-integrin therapy. Pre-escalation inflammatory markers included median CRP of 9.55 mg/Land median fecal calprotectin of 340 μg/mg. Median UST trough prior to escalation was 1.3 μg/mL(IQR 0.8–2.1). Overall, half (19/38) of patients who underwent dose escalation met the primary composite outcome of disease response and 50% (12/24) of patients with active perianal disease showed evidence of improvement after escalation. 60% (6/10) of the patients on steroids at time of escalation achieved steroid-free response. 72% (8/11) of those who underwent follow-up endoscopy showed endoscopic improvement. 50% (6/12) of patients who had radiographic follow-up showed signs of improvement. 27% (9/33) had normalization of CRP after dose escalation. 8% (3/38) patients required an IBD-related surgery after dose escalation. Two patients had adverse events recorded (see table 3). Conclusion Patients who underwent UST dose escalation demonstrated improvement in perianal disease as well as steroid-free clinical, endoscopic, radiographic, and biochemical response. No increase in serious adverse events was seen in this cohort. Dose escalation is an effective option for non-responders to every 8-week dosing.