P1006 Effectiveness of Upadacitinib in Patients with Baseline Active Extraintestinal Manifestations and Inflammatory Bowel Disease. A multicenter retrospective study
Authors: Fuentes-Valenzuela E , Chivato Martín-Falquina I , Caballero-Mateos A M , Botella Mateu B , Fernández-Prada S , Calvo Moya M , Rubín de Célix C , Olmedo Moreno C , Suarez Ferrer C , Iborra M , Carballo-Folgoso L , Barrero S , Martín-Arranz M D , Rafael de la Cruz Esteban D , Yagüe C , García M J , Saiz-Chumillas R M , Sicilia B , Segarra-Ortega J X , Ruíz Ramírez M Á , García de la Filia I , Betoré Glaría E , Andreo Vidal B E , Velayo B , López-Martín M D C , Calvache Rodríguez A , Gil Santana M , Barrio J 
Published: January 2025

Background

Upadacitinib has shown to be more effective than placebo for treating extraintestinal manifestations (EIM) in post-hoc analyses. However, real-world data on the effectiveness of upadacitinib in patients with inflammatory bowel disease (IBD) and EIMs are lacking.

Methods

A multicenter, retrospective and observational study was conducted at 18 Spanish hospitals. Patients with IBD and active EIMs when initiating upadacitinib were eligible. The primary outcome was EIM improvement at weeks 8-12. The EIM assessment was based on the physician’s subjective evaluation and categorized into clinical remission, partial response, nonresponse and worsening. EIM improvement was defined as either clinical remission or partial response. Axial arthropathy, peripheral arthropathy, pyoderma gangrenosum, erythema nodosum, sweet syndrome, aphthous stomatitis, uveitis, episcleritis, primary sclerosing cholangitis and bronchiectasis were considered. In patient experiencing &gt;1 EIM, all had to be resolved or improved to be considered. If not, the worst outcome was recorded. Patients’ visits were scheduled at weeks 0, 8-12, and 6 months. Multivariate analysis was performed to find factors associated with EIM improvement at w8-12.

Results

a total of 123 patients were included, 89 patients with Crohn’s Disease (72.4%), 65 females (52.9%) with a median age of 46.1 years (IQR 35.9-56.7). Ninety-three patients (75.56%) initiated upadacitinib due to luminal activity and active EIMs and 30 patients (24.4%) exclusively due to EIMs. All patients were bio-experienced with 64 patients previously treated with ≥3 biologics. Forty patients (32.5%) presented ≥2 active baseline EIMs.

At w8-12, 79 patients (64.2%) achieved EIM improvement, 34 patients (27.6%) clinical remission, 45 patients (36.6%) partial response, 43 patients (35 %) nonresponse and worsening in 1 patient. Improvement at weeks 8-12 was higher for patients initiating Upadacitinib due to exclusively active EIMs (80% vs 59.1 %, OR 0.2 95% CI 0.1-0.4; p=0.04). IBD clinical remission at w8-12 was achieved in 75 patients (61%).

Evaluation at 6 months was available for 82 patients, 58 patients (70.7%) presented EIM improvement, 35 patients (42.7%) clinical remission, 23 patients (28.1%) partial response, 16 patients (19.5%) nonresponse and 8 patients (9.8%) worsening. IBD clinical remission at 6 months was achieved in 51 patients (62.2%).

During the follow-up, Upadacitinib was ceased in 22 patients (17.9%). Adverse events were detected in 32 patients (26%) and 5 patients (5.7%) experienced worsening of previous inactive EIMs.

Conclusion

Upadacitinib was highly effective in short-term for treating bio-experienced patients with active EIMs, particularly for patients without luminal activity.