Upadacitinib may offer a therapeutic option for patients with difficult-to-treat perianal Crohn’s disease (pCD) who have failed multiple advanced therapies, according to real-world data from a recent multicentre French cohort.

pCD is among the most challenging disease manifestations to manage, with limited evidence available to guide treatment beyond anti-tumour necrosis factor (TNF) therapy.

While the Janus kinase inhibitor upadacitinib has demonstrated efficacy in luminal disease, data in patients with perianal involvement have been scarce.

To address this evidence gap, researchers from the Therapeutic Study Group for Inflammatory Diseases of the Digestive Tract evaluated the one-year effectiveness and safety of upadacitinib in patients with active pCD treated in routine clinical practice.

Published in the journal Alimentary Pharmacology & Therapeutics, the retrospective multicentre cohort study included consecutive adults who had active pCD treated across 13 French centres between September 2022 and August 2025.

The primary outcome was clinical remission at 52 weeks, defined as the absence of fistula drainage and healing of anal ulcerations or fissures without the need for additional dedicated therapy.

Secondary outcomes included clinical response, radiological outcomes, need for surgery or hospitalisation, seton removal and safety.

Upadacitinib and one-year remission

The study enrolled 59 patients with active pCD, of whom 43 had fistulising disease and 16 had isolated anal ulcerations. The group was highly treatment-experienced: all patients had received at least one advanced therapy, 95% had failed two or more biologics, and 88% had previously been treated with infliximab. More than two-thirds had undergone prior perianal surgery.

After a median follow-up of 49 weeks, clinical remission was achieved in 15 of 59 patients (25%), while 32% achieved a clinical response with upadacitinib. Among patients with fistulising pCD, the one-year remission and response rates were 26% and 30%, respectively.

Similar outcomes were observed in those with isolated anal ulcerations, with 25% achieving complete healing by 12 months.

Clinical response was greatest early in treatment, occurring in 63% of patients with fistulising disease at three months, although response rates declined over time to 49% at six months and 30% at one year.

Seton removal was achieved in 29% of patients who had a draining seton at baseline. During follow-up, 17% of patients required perianal surgery and 19% experienced a pCD-related hospitalisation.

Favourable safety in real-world practice

Radiological assessment was available for 13 patients with fistulising disease. Magnetic resonance imaging (MRI) response was documented in 69% of patients, although MRI remission was achieved in only one patient. No baseline clinical factors were found to predict treatment success.

Upadacitinib was generally well tolerated and adverse events occurred in 25% of patients, with acne the most commonly reported. Three serious adverse events were recorded, all related to CD exacerbations.

Importantly, no malignancies, thromboembolic events, major adverse cardiovascular events, severe infections, herpes zoster cases or deaths were reported during follow-up.

The authors noted several limitations, including the retrospective design, a relatively small sample size, and the lack of centrally reviewed MRI assessments. The study was also underpowered to identify predictors of response.

Nevertheless, the study’s multicentre design and one-year follow-up offered valuable real-world evidence in a patient population with limited treatment options, and the authors concluded that upadacitinib represents a potential treatment option for anti-TNF-refractory pCD.

Comparative studies evaluating upadacitinib alongside ustekinumab and risankizumab are needed to help define the optimal treatment strategy for this challenging patient population, the authors concluded.

Reference
Richard N et al. One-Year Effectiveness of Upadacitinib in Perianal Crohn's Disease: A Real-World GETAID Study. Aliment Pharmacol Ther 2026;April 27:doi:10.1111/apt.70682.