Vedolizumab Is Effective for the Treatment of Chronic Inflammatory Conditions of the Pouch in a Prospective Multicenter Study

Introduction: Vedolizumab has recently demonstrated efficacy in the treatment of chronic pouchitis in a randomized, placebo-controlled trial (EARNEST). Often, patients treated in real-world settings differ from those in clinical trials, thus we compared the clinical characteristics of patients treated with vedolizumab for chronic inflammatory conditions of the pouch in a prospective registry to those in the EARNEST study as well as the overall effectiveness of vedolizumab in this setting. Methods: Patients with chronic pouchitis or Crohn’s disease of the pouch (CDP) were recruited from nine centers at the time of initiation of vedolizumab for their pouch-related disorder. Clinical assessments were performed at enrollment and 3 and 6 months after enrollment. The diagnosis of CDP was made by the enrolling physician and was based on the following criteria: inflammation of the pre-pouch ileum, strictures involving the pouch or pre-pouch ileum, and/or fistulae involving the pouch or pre-pouch ileum. Clinical remission was defined as a clinical modified Pouchitis Disease Activity Index (mPDAI) score <2 with both the bowel frequency and urgency subscores <1. Results: Among 18 patients initiating vedolizumab, 9 (50%) had chronic pouchitis and 9 (50%) had CDP. At the time of induction with vedolizumab, 8 (44%) patients were using antibiotics, with 5 (28%) patients having prior exposure to tumor necrosis factor alpha antagonist (anti-TNF) therapy after IPAA, 2 (11%) having prior exposure to ustekinumab after IPAA and 1 (6%) having prior exposure to tofacitinib after IPAA (Table 1). Among patients with eligible follow-up data, at 3 months after induction with vedolizumab, 6 of 16 (38%) patients were in clinical remission and at 6 months, 7 of 11 (64%) were in clinical remission (Figure 1). Similar rates of effectiveness were seen in patients with chronic pouchitis and CDP at both time points. Conclusion: In a prospective evaluation of the real-world effectiveness of vedolizumab for the treatment of chronic inflammatory conditions of the pouch, patients with both chronic pouchitis and CDP demonstrated favorable response to vedolizumab. In a population that demonstrated several potential indicators of refractory disease, vedolizumab showed a consistent treatment effect and should receive strong consideration for patients with chronic inflammatory conditions of the pouch. Table 1. - Ileal pouch-anal anastomosis (IPAA); tumor necrosis factor alpha (TNF) Real-World Population (n=51) EARNEST (n=51) Diagnosis Chronic Pouchitis 9 50 51 100 Crohn's disease of the pouch 9 50 0 0 Age, median (range) 57 21-83 42 19-67 Male Sex Race White 17 94 44 86 Black or African American 1 6 1 2 Asian 0 0 6 12 Multiracial 0 0 0 0 Data Missing 0 0 2 4 Continuous use of antibiotics immediately before baseline 8 44 29 57 Time since IPAA < 7 years 6 35 16 31 > 7 years 11 65 35 69 Missing 1 Treatment failure with a TNF antagonist after IPAA 5 28 15 29 Treatment failure with ustekinumab after IPAA 2 11 0 0 Treatment failure with tofacitinib after IPAA 1 6 0 0 Figure 1.: Clinical remission among patients treated with vedolizumab for chronic inflammatory conditions of the pouch, assessed at 3 and 6 months post induction Note: historical placebo rate from week 14 and week 34 assessment in EARNEST.