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Publications

Journal Article Ahead of print 2 citations

PubMed: 42720163 DOI: 10.1111/apt.70970

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).

Aliment Pharmacol Ther

Authors: Brigida Barberio, Ferdinando D'Amico, Lucrezia Laterza, Cristina Bezzio, Gabriele Dragoni, Anna Viola, Alessia Todeschini, Mariabeatrice Principi, Sara Onali, Chiara Viganò, Maria Cappello, Giammarco Mocci, Angelo Viscido, Giorgia Bodini, Davide Giuseppe Ribaldone, Irene Marafini, Daniela Pugliese, Alessandro Massari, Simone Saibeni, Luca Pastorelli, Laura Melotti, Irene Maria Bambina Bergna, Antonietta Gerarda Gravina, Federico Desideri, Manuela Merli, Lorenzo Bertani, Rocco Spagnuolo, Nicola Imperatore, Concetta Ferracane, Alessandro Quadarella, Imma Di Luna, Vincenza Tortorella, Silvia Mazzuoli, Carla Felice, Paola Balestrieri, Daniele Balducci, Annalisa Aratari, Andrea Buda, Silvio Danese, Franco Scaldaferri, Alessandro Armuzzi, Fabiana Zingone, Javier Chahuan, Edoardo V Savarino

Affiliations

  • Gastroenterology Unit, Azienda Ospedale-Università di Padova, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy.
  • IRCCS San Raffaele Hospital, Gastroenterology and Endoscopy, Milan, Italy.
  • Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Medicina Interna e Gastroenterologia, CEMAD Centro Malattie Dell'apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
  • IBD Center, IRCCS Humanitas Research Hospital, Milan, Italy.
  • Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
  • Gastroenterology Unit, IBD Referral Centre, Careggi University Hospital, Florence, Italy.
  • IBD-Unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
  • IBD Unit, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy.
  • Gastroenterology Unit, Azienda Policlinico-Universitaria di Bari, University of Bari, Bari, Italy.
  • Gastroenterology Unit, University Hospital of Monserrato, Cagliari, Italy.
  • Gastroenteorology Unit, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.
  • Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
  • Division of Gastroenterology, AORN "Brotzu" Hospital, Cagliari, Italy.
  • Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L'aquila, L'Aquila, Italy.
  • Division of Gastroenterology, Department of Internal Medicine and Medical Specialties, IRCCS "San Martino" Hospital, University of Genoa, Genoa, Italy.
  • Department of Medical Sciences, University of Turin, Turin, Italy.
  • Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico Tor Vergata, Rome, Italy.
  • Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
  • UOS Gastroenterologia, Ospedale Isola Tiberina Gemelli Isola, Rome, Italy.
  • IBD UNIT-CEMAD (Centro Malattie Apparato Digerente), Medicina Interna e Gastroenterologia, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
  • Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences L. Sacco University Hospital, University of Milan, Milan, Italy.
  • IBD Unit, Ospedale di Rho, Gastroenterology Unit, ASST Rhodense, Rho, Italy.
  • Ospedale San Paolo, Hepatology and Gastroenterology Unit, ASST Santi Paolo e Carlo, Milan, Italy.
  • IBD Unit, Policlinico Di Sant'orsola, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.
  • Digestive Endoscopy and Gastroenterology Department, Ospedale A. Manzoni Hospital, Lecco, Italy.
  • Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.
  • Department of Gastroenterology, Bolzano Hospital, Bolzano, Italy.
  • Department of Translational and Precision Medicine, Università Degli Studi di Roma Sapienza, Rome, Italy.
  • Gastroenterology Unit-Department of Internal Medicine, Tuscany North West ASL - PO Pontedera, Pontedera, Italy.
  • Health Sciences Department, Magna Graecia University, Catanzaro, Italy.
  • Gastroenterology and Endoscopy Unit, Santa Maria Delle Grazie Hospital, Pozzuoli (Naples), Italy.
  • Gastroenterology Unit, "Vittorio Emanuele" Hospital, AOU Policlinico San Marco, Catania, Italy.
  • Department of Gastroenterology and Endoscopy, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
  • Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona, Italy.
  • Gastroenterology Unit, A.O.O.R. "Papardo Piemonte", Messina, Italy.
  • Gastroenterology Department, Monsignor Raffaele DIMICCOLI Hospital, Barletta, Italy.
  • Ca' Foncello Hospital, AULSS2 Marca Trevigiana, Treviso, Italy.
  • Department of Medicine (DIMED), University of Padova, Padova, Italy.
  • Gastroenterology Unit, Fondazione Policlinico Campus Bio-Medico, Rome, Italy.
  • Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, Ancona, Italy.
  • IBD Unit, San Filippo Neri Hospital, Rome, Italy.
  • Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. Maria del Prato Hospital, Feltre, Italy.
  • Gastroenterology and Endoscopy, Vita Salute San Raffaele University, Milan, Italy.
  • Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

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.

MeSH

Safety, Crohn Disease, Inflammatory Bowel Diseases, Pharmacology, Therapeutics, Prospective Studies