Upadacitinib Shows Real-World Benefit in Perianal Crohn’s Disease : Clin Gastroenterol Hepatol | May 2026

Introduction

Perianal Crohn’s Disease remains one of the most disabling and treatment-refractory manifestations of inflammatory bowel disease, frequently associated with fistulas, abscesses, recurrent surgery and impaired quality of life. Although anti-TNF therapy has historically been the cornerstone of fistulizing disease management, many patients experience incomplete response or secondary loss of efficacy. Upadacitinib has demonstrated efficacy in luminal Crohn’s disease, and post-hoc analyses from phase III trials suggested potential benefit in perianal disease, but real-world data—particularly radiologic outcomes—have been limited.

Problem Statement

Management of perianal Crohn’s disease remains challenging, especially in patients with prior biologic exposure and longstanding fistulizing disease. Whether upadacitinib can achieve meaningful fistula healing and radiologic improvement in routine clinical practice has not been well established.

Summary

This multicenter North American retrospective cohort study evaluated 125 adults with active perianal Crohn’s disease treated with upadacitinib across 10 tertiary centers. The cohort represented a highly refractory population, with nearly half having complex fistulas and more than three-quarters previously exposed to anti-TNF therapy. Clinical outcomes were assessed using the Perianal Disease Activity Index (PDAI), alongside inflammatory biomarkers and pelvic MRI findings.

Upadacitinib demonstrated clinically meaningful effectiveness in this difficult-to-treat population. Approximately 46% of patients achieved clinical response, while nearly 40% achieved clinical remission. Importantly, radiologic improvement was documented in more than half of patients undergoing pelvic MRI assessment, and complete radiologic healing occurred in approximately 12%, representing one of the first real-world MRI-based evaluations of upadacitinib in fistulizing Crohn’s disease. Rates of hospitalization and perianal surgery during follow-up remained relatively low, supporting meaningful disease control in routine practice.

Treatment effectiveness appeared strongly influenced by prior biologic exposure and disease chronicity. Anti-TNF–naïve patients achieved substantially higher clinical response rates compared with previously exposed individuals, suggesting greater efficacy earlier in the disease course. Similarly, shorter perianal disease duration was associated with improved outcomes, reinforcing the concept that early aggressive intervention may improve fistula healing potential before irreversible fibrotic remodeling develops. Multivariable analysis identified prior anti-TNF exposure as a significant negative predictor of response.

Overall, this study provides important real-world evidence supporting upadacitinib as a therapeutic option for perianal Crohn’s disease, particularly in patients with earlier disease and limited biologic exposure. The inclusion of radiologic outcomes strengthens the clinical relevance of the findings and supports further prospective controlled studies evaluating JAK inhibition for fistulizing Crohn’s disease management.