S1631 Real-World Experience of Upadacitinib in Setting of Ileal Pouch Anal Anastomosis

Introduction: Pouchitis is the most common inflammatory complication of ileal pouch anal anastomosis (IPAA), and a proportion of individuals will develop chronic antibiotic refractory pouchitis (CARP) or Crohn’s disease (CD) of the pouch, which may require immune-modifying therapies. Upadacitinib (UPA) is a selective Janus Kinase 1 inhibitor with demonstrated efficacy in moderate to severe CD. Data for its use in the setting of IPAA remain limited. Methods: We performed a retrospective review of adult patients treated with UPA for CARP or CD of the pouch at Mayo Clinic Rochester. Primary outcome was clinical remission within one year of UPA start based on the clinical portion of the modified pouchitis disease activity index (mPDAI) (clinical mPDAI ≤2) and endoscopic response (reduction in endoscopic pouch score [EPS]) within one year. Secondary endpoints included adverse events. Results: A total of 18 patients were treated with UPA for pouchitis (83.3% CD, 16.7% CARP) after a median of 12 years (IQR, 4.3-17.0) following IPAA (mean age 40 years, 38.9% male). The majority (88.9%) received 45 mg for induction for 8 (31.3%) or 12 (56.3%) weeks, followed by 30 mg (83.3%) or 15 mg (16.7%) for maintenance. All patients were tumor-necrosis factor inhibitor exposed. At baseline, the mean clinical mPDAI was 3.1. At 12 weeks of follow up (n = 8), the average mPDAI was 2.4. Of the patients with available follow-up within 1 year (n = 12), 58.3% were in clinical remission. On baseline pouchoscopy (n = 8), the mean EPS was 9.7. Of the 5 patients who had both baseline and follow-up pouchoscopy, 3 (60%) achieved endoscopic response. Three patients (16.7%) required surgery for either pouch excision (n = 2) or diverting loop ileostomy (n = 1). Adverse events (AE) were reported in 28.6% (4/14), including pulmonary embolus (n = 1), acne (n = 1), anemia (n = 1), and infection (n = 1) the latter being the only AE resulting in UPA discontinuation. At 1 year of follow-up, 7 patients (38.8%) discontinued UPA due to lack or loss of response (n = 6) or adverse event (n = 1). Conclusion: This retrospective study shows that UPA may represent an effective option for the treatment of pouchitis following IPAA. Adverse events leading to discontinuation of UPA were on par with what is documented in the literature with only one thromboembolic event in a patient who was hospitalized. Large scale prospective studies are needed to further evaluate the efficacy and safety of UPA as a treatment option in this unique population.