Lancet Gastroenterol Hepatol. 2023 Sep;8(9):853-859.doi: 10.1016/S2468-1253(23)00154-1. Epub 2023 Jul 6.

Tommaso Lorenzo Parigi ¹, Ferdinando D'Amico ², Maria T Abreu ³, Axel Dignass ⁴, Iris Dotan ⁵, Fernando Magro ⁶, Anne M Griffiths ⁷, Vipul Jairath ⁸, Marietta Iacucci ⁹, Gerassimos J Mantzaris ¹⁰, Colm O'Morain ¹¹, Walter Reinisch ¹², David B Sachar ¹³, Dan Turner ¹⁴, Takayuki Yamamoto ¹⁵, David T Rubin ¹⁶, Laurent Peyrin-Biroulet ¹⁷, Subrata Ghosh ¹⁸, Silvio Danese ¹⁹

Author information

¹Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy; Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

²Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.

³Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.

⁴Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt, Germany.

⁵Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

⁶Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal.

⁷Division of Gastroenterology, SickKids Hospital, University of Toronto, Toronto, ON, Canada.

⁸Departments of Medicine, Epidemiology and Biostatistics, Western University, London, ON, Canada.

⁹Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.

¹⁰Department of Gastroenterology, GHA Evangelismos-Polykliniki, Athens, Greece.

¹¹Department of Gastroenterology, Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland.

¹²Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

¹³The Dr Henry J Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

¹⁴Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

¹⁵IBD Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan.

¹⁶University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.

¹⁷University of Lorraine, Inserm, NGERE, F-54000, Nancy, France.

¹⁸APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.

¹⁹Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy; Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: danese.silvio@hsr.it.

Abstract

Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies.