Real‐World Effectiveness and Safety of Upadacitinib in Patients With Crohn's Disease—A Multicentre Prospective Study From the Italian Group for the Study of Inflammatory Bowel Diseases ( IG ‐ IBD )

Year: 2026

Type: article

Abstract: BACKGROUND AND AIMS: Upadacitinib is an oral selective JAK1 inhibitor approved for moderate-to-severe Crohn's disease (CD), but real-world prospective multicentre data in advanced therapy-experienced (AT-experienced) patients are limited. The UPGRADE-CD study evaluated its effectiveness and safety. METHODS: In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT-experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid-free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose. RESULTS: A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 (p = 0.07). Steroid-free clinical response rose from 53.8% to 63.5% (p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred. CONCLUSIONS: Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.

Source: Alimentary Pharmacology & Therapeutics

DOI: 10.1111/apt.70970

Institutions: University of Padua, Azienda Ospedale - Università Padova, IRCCS Ospedale San Raffaele, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Humanitas University, IRCCS Humanitas Research Hospital, Azienda Ospedaliero-Universitaria Careggi, University of Florence, University of Messina, Ospedale Sacro Cuore Don Calabria, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, University of Bari Aldo Moro, Azienda Ospedaliero-Universitaria Cagliari, Azienda Ospedaliera San Gerardo, University of Palermo, Azienda Ospedaliera G. Brotzu, University of L'Aquila, Ospedale Policlinico San Martino, University of Genoa, University of Turin, University of Rome Tor Vergata, Policlinico Tor Vergata, University of Milan, Luigi Sacco Hospital, ASST Fatebenefratelli Sacco, Aziende Socio Sanitaria Territoriale Rhodense, Ospedale San Paolo, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, Alessandro Manzoni Hospital, Aziende Socio Sanitarie Territoriali di Lecco, University of Campania "Luigi Vanvitelli", Ospedale di Bolzano, Sapienza University of Rome, Magna Graecia University, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco", Fondazione Poliambulanza Istituto Ospedaliero, Azienda Socio Sanitaria Territoriale di Cremona, Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte, AULSS 2 Marca Trevigiana, Ca' Foncello Hospital, Campus Bio Medico University Hospital, Marche Polytechnic University, Ospedale San Filippo Neri, Hospital of Prato, Vita-Salute San Raffaele University, Pontificia Universidad Católica de Chile

Language: English

Topic: Inflammatory Bowel Disease

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W7212176033