Background/Objectives: Data on the real-world effectiveness and safety of selective JAK inhibitors (JAKis) in ulcerative colitis (UC) and Crohn's disease (CD) are limited. Methods: We conducted a multicentre, retrospective study to assess clinical, biochemical, and endoscopic outcomes of selective JAKis in bio-experienced UC and CD. Results: A total of 246 patients (mean age: 40.5 ± 14.5 years; 131 UC and 115 CD) were included with a median follow-up of 7.5 months. Among the CD patients receiving upadacitinib (n = 115), 76.2% achieved clinical remission (CR) at week 12. Furthermore, 59.5% of the upadacitinib-treated UC patients (n = 100) experienced CR at week 8. Corticosteroid-free CR (CSFCR) was achieved by 76.9% of the CD patients and 80.6% of the UC patients at week 24, while 50.0% and 36.1% experienced endoscopic remission. At week 52, 66.7% of the CD and 86.2% of the UC patients achieved CSFCR, whereas 54.5% and 52.9% had endoscopic remission. In UC, the effectiveness of upadacitinib was not compromised by prior tofacitinib failure, while the upadacitinib-treated CD patients with stricturing and penetrating disease were less likely to achieve CR by the end of the induction phase (p = 0.04). C-reactive protein (p[CD] < 0.0001; p[UC] < 0.0001) and faecal calprotectin (p[CD] < 0.0001; p[UC] = 0.02) decreased significantly in both patient groups as early as week 2. Among the filgotinib-treated UC patients (n = 31), 28.6% were in CR at week 12. At week 24 and 52, 59.1% and 60% achieved CSFCR, while 0.0% and 20.0% had endoscopic remission. Both C-reactive protein (p = 0.04) and faecal calprotectin (p = 0.04) decreased significantly by week 12. Hyperlipidaemia (9.7-9.8%) was the most common adverse event. Conclusions: Selective JAKis are rapidly effective and safe for treating refractory, moderate-to-severe CD and UC.

Center for Gastroenterology University of Szeged 6725 Szeged Hungary

Clinical and Research Centre for Inflammatory Bowel Diseases 19000 Prague Czech Republic

Department of Biomedical Sciences Humanitas University 20072 Milan Italy

Department of Coloproctology Irkutsk Regional Hospital Irkutsk 664528 Russia

Department of Gastroenterology and Hepatology Copenhagen University Hospital Herlev and Gentofte 2730 Herlev Denmark

Department of Gastroenterology Hungarian Defence Forces Military Hospital 1062 Budapest Hungary

Department of Gastroenterology with IBD Unit Clinical Hospital 2 35301 Rzeszów Poland

Department of Internal Medicine and Oncology Semmelweis University 1085 Budapest Hungary

Department of Surgery Oncology and Gastroenterology University of Padua 35124 Padua Italy

Division of Gastroenterology McGill University Health Centre Montreal QC H4A 3J1 Canada

Division of Gastroenterology University Hospital of Ioannina 45500 Ioannina Greece

Federal Scientific Center of Surgery and Traumatology Irkutsk 664003 Russia

Gastroenterology Department of Clinical Medicine and Surgery University of Naples Federico 2 80131 Naples Italy

Gastroenterology Unit Azienda Ospedale Università of Padua 35128 Padua Italy

Gastroenterology Unit Rho Hospital ASST Rhodense 20017 Milan Italy

General Hospital of Athens G Gennimatas 11527 Athens Greece

HCEMM USZ Translational Colorectal Research Group 6725 Szeged Hungary

IBD Center IRCCS Humanitas Research Hospital 20089 Milan Italy

Moscow Clinical Scientific Center Named after A S Loginov Moscow 111123 Russia

Northern Care Alliance NHS Foundation Trust Manchester M6 8HD UK

Research Institute of Health Organization and Medical Management Moscow 115088 Russia

State Scientific Centre of Coloproctology Named after A N Ryzhyh Moscow 123423 Russia

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