P081 AN EVALUATION OF VEDOLIZUMAB “PARTIAL RESPONDERS”: QUANTIFYING BENEFIT OF SHORTENED DOSING INTEVALS IN ULCERATIVE COLITIS

Abstract

Abstract Introduction Six years ago, the Gemini pharma trial reported no significant difference in response rate between Ulcerative Colitis (UC) patients randomized to q8week vedolizumab dosing vs q4weeks.1 In Gemini, patients were randomized based on response after 6 week induction, but post-hoc analysis and real world data report an average response time of 19 weeks.2 Patients in Gemini may have been dose escalated too early, which minimized potential difference between groups. Previous studies indicate dose intensification benefits patients who initially achieved remission on standard dosing but lost response.3 To our knowledge, the benefit of dose escalation in patients who achieve partial response to standard dosing has not been investigated. Methods In this single institution retrospective review, 90 patients with UC who completed vedolizumab induction between 1/2017-1/2019 were included for analysis. Collected variables included subject demographics, disease severity, location, and duration, prior anti-TNF use, corticosteroid dependence, fecal calprotectin, CRP, albumin, and hemoglobin. Primary outcomes collected were time to response (decrease in partial mayo score by ≥2), and time to remission (partial mayo score <2) for patients on standard vs escalated dosing. Results 52/90 (57.8%) patients achieved and maintained remission on q8weeks. 30/90 (33.3%) had a partial response to q8week dosing, 3/90 patients achieved remission on q8week dosing but relapsed, and 5/90 had no response. 22/33 (66.7%) patients with either partial q8week response (19 patients) or relapse after remission on q8week (3 patients) were dose escalated. Of the 19 “partial responders” who were dose escalated, 8 (42.1%) achieved remission, 8 (42.1%) achieved partial response, and 2 had no response (10.5%). Of the “partial responders” who were not dose escalated, none achieved remission. Average time to remission with standard dosing was 42.3 weeks. Average time to dose escalation in partial responders was 54 weeks. The average time to remission after dose escalation was 27.7 weeks. There were no identifiable clinical predictors of poor response, including: BMI >24.9 (p=0.22) or >30 (p=0.44), prior anti-TNF use (p= 0.53), disease location (p=0.61), or disease duration (± 5 years, p=0.85). Conclusion Our results suggest escalation to q4week is a viable treatment option for UC patients who partially respond to vedolizumab at standard dosing. This is supported not only by the high ratio of escalated patients achieving remission, but also the lack of remission in the 11 “partial responders” not dose escalated. We were not able to identify any clinical predictors that may impact response to vedolizumab prior to induction dosing, but is likely of less importance given the predictability of early trough levels. We feel that our study supports dose escalation in patients with partial response, and this knowledge can be used to bolster confidence in early dose escalation as vedolizumab trough levels move into routine practice.