Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn's Disease: A Post Hoc Analysis of 3 Phase 3 Trials.

BACKGROUND & AIMS: Efficacy of upadacitinib, an oral Janus kinase inhibitor, for moderate-to-severe Crohn's disease was demonstrated in phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials; this post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in these studies. METHODS: Patients were randomized (2:1) to once daily upadacitinib 45 mg or placebo for 12 weeks. Upadacitinib 45 mg clinical responders were rerandomized (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks. In patients with fistulas (any and perianal), resolution of drainage, closure of external openings, clinical remission, endoscopic response, and safety were assessed. RESULTS: Of 1021 patients in U-EXCEL and U-EXCEED, 143 (14.0%) had any fistulas at baseline (66 draining); of these, most (n = 128) had perianal fistulas (56 draining). Greater proportions of patients receiving upadacitinib vs placebo achieved resolution of drainage of perianal fistulas at the end of induction (placebo: 5.6%, n/n = 1/18; upadacitinib 45 mg: 44.7%, n/n = 17/38; P = .003) and maintenance (placebo: 0%, n/n = 0/11; upadacitinib 15 mg: 28.6%, n/n = 4/14; P = .105; upadacitinib 30 mg: 23.1% n/n = 3/13; P = .223) and closure of perianal fistula external openings (for induction, placebo: 4.8%, n/n = 2/42; upadacitinib 45 mg: 22.1%, n/n = 19/86; P = .013; for maintenance, placebo: 0%, n/n = 0/30; upadacitinib 15 mg: 18.8%, n/n = 6/32; P = .024; upadacitinib 30 mg: 16.0%, n/n = 4/25; P = .037). CONCLUSION: Patients with fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo. CLINICALTRIALS: gov, Numbers: NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE).

The Role of Exenterative Surgery in Advanced Urological Neoplasms.

Pelvic exenterative surgery is both complex and challenging, especially in the setting of locally recurrent disease. In recent decades, improved surgical techniques have facilitated more extensive resection of both locally advanced and recurrent pelvic malignancies, but its role in urological cancer surgery is highly selective. However, it remains an important part of the armamentarium for the management of bladder and prostate cancer cases where there is local invasion into adjacent organs or localized recurrence. Better diagnostics, reconstructive options and centralized care have reduced associated morbidity considerably, and it is still used rarely in palliative settings. Despite this, there is sparse prospective evidence reporting on long-term oncological or quality of life outcomes.