Multicentre, prospective, observational study on the effectiveness and safety of upadacitinib for active perianal fistulising Crohn's disease in patients with prior anti-tumour necrosis factor failure: a study protocol.

BACKGROUND: Perianal fistulising Crohn's disease (pfCD) is a debilitating phenotype and remains a therapeutic challenge. Current guidelines recommend anti-tumour necrosis factor agents as first-line therapy for pfCD; however, there is still no consensus on the optimal pharmacological strategy once anti-TNF therapy fails. Upadacitinib, an oral selective Janus kinase 1 inhibitor, has demonstrated efficacy in moderate-to-severe Crohn's disease. Nevertheless, real-world data specifically addressing its effectiveness and safety in the refractory pfCD population remain scarce. This study aims to evaluate the real-world effectiveness and safety of upadacitinib in patients with active pfCD who have failed anti-TNF therapy. METHODS AND ANALYSIS: This is a multicentre, prospective, observational cohort study. A total of 90 adult patients with Crohn's disease-associated perianal fistulas with active drainage and refractory to prior therapy with infliximab or adalimumab will be enrolled. Patients with severe luminal disease, undrained abscesses >2 cm, anal stenosis or diverting stomas will be excluded. Participants will receive upadacitinib 45 mg/day during the induction phase, followed by 15 or 30 mg/day during maintenance. All treatment decisions are made according to routine clinical practice and local product labels, not mandated by the study protocol, including upadacitinib dosing, dose adjustments and concomitant therapies. The primary outcome is a composite of clinical and radiological fistula response at week 12. Secondary outcomes, assessed at weeks 12 and 52, include perianal fistula-related, CD-related and safety outcomes. ETHICS AND DISSEMINATION: Shanghai Jiao Tong University School of Medicine, Renji Hospital Ethics Committee has reviewed and approved this study (Approval No: LY2025-024-A). Findings will be disseminated through publication in peer-reviewed journals, presentations at scientific conferences and summaries provided to the participating institutions and relevant patient communities. TRIAL REGISTRATION NUMBER: ChiCTR2600117355.