Effectiveness of Upadacitinib for Inflammatory Bowel Disease Patients With Pouchitis: Prospective Real-World Experience

Introduction: Pouchitis occurs in up to 80% of patients within 2 years of ileal pouch-anal anastomosis (IPAA). Upadacitinib (UPA) is a novel, selective Janus kinase-1 inhibitor that has received regulatory approval for moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD). However, the effectiveness and safety of UPA therapy for patients with pouchitis is not known. Here we present our real-world experience with UPA in patients with antibiotic-resistant pouchitis. Methods: We performed a prospective, real-world analysis of clinical outcomes for patients with IPAA who had antibiotic-resistant pouchitis and were treated with UPA. Clinical monitoring to assess effectiveness and safety occurred at pre-determined intervals at weeks 0, 2, 4, and 8 and included fecal calprotectin and a modified Pouchitis Disease Activity Index (mPDAI included clinical disease activity measures only: stool frequency, fecal urgency or abdominal cramps, rectal bleeding, and fever). Clinical remission was defined as mPDAI < 2. Clinical response was defined as a reduction in mPDAI ≥ 3 points from baseline. Treatment- related and serious adverse events (AEs) were assessed for at each interval follow-up. Results: 10 patients with antibiotic-resistant IPAA received UPA 45 mg/d. 5 patients were treated with UPA for endoscopically active disease and 5 were treated for clinically and/or biochemically active disease (Table 1). 2 patients were in clinical remission at the time of UPA initiation. By week 8, 6 patients (60%) achieved steroid-free clinical remission; 1 patient achieved clinical remission but remained on prednisone 40mg daily; 3 patients (30%) with active disease at baseline did not achieve clinical response or remission by week 8. All patients were continued on UPA after the week 8 timepoint. 3 patients experienced AEs which required temporary discontinuation of UPA. Upon resuming UPA therapy, 1 patient experienced loss of response and was switched to ustekinumab, and 2 patients continued UPA therapy. There were 2 serious adverse events: 1 patient required hospital admission for a novovirus infection and 1 unvaccinated patient developed shingles. 1 patient developed a superficial vein thrombus. No other serious infections or MACE occurred. Conclusion: In this prospective, real-world experience we describe UPA to be an effective and overall safe option for the treatment of antibiotic-resistant pouchitis. Longer term study is ongoing. Table 1. - Demographics and disease monitoring of antibiotic-refractory pouchitis patients initiated on upadacitinib at Week 0 and Week 8 Case Age Sex Previous biologic therapies EIMs and comorbidities Indication for upadacitinib mPDAI at Week 0 mPDAI at Week 8 FCP at Week 0 (ug/g) FCP at Week 8 (ug/g) AEs 1 45 F IFX, ADA, UST, Hidradenitis suppurativa Endoscopically active disease 3 1 17.5 None 2 43 M IFX, ADA None Biochemically active disease 1 0 258 None 3 45 M IFX, ADA, VED None Clinically active disease 3 3 569.71 800 None 4 49 M IFX, ADA, VED, TOF None Endoscopically active disease 4 2 220 98.5 None 5 31 M IFX, ADA, UST, None Endoscopically active disease 1 1 225 None 6 52 M IFX None Clinically active disease 3 0 None 7 33 F IFX, VED None Endoscopically active disease 4 0 50 Shingles 8 37 M IFX, ADA, UST Inflammatory arthropathy Endoscopically active disease 3 0 1353 None 9 49 M IFX, ADA, UST, VED Inflammatory arthropathy Clinically active disease 3 2 645 72 Superficial vein thrombus 10 43 M IFX None Clinically active disease 3 0 617 Novovirus infection EIMS, extraintestinal manifestations; mPDAI, modified pouchitis disease activity index; FCP, fecal calprotectin; AEs, adverse events.