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World J Gastroenterol. Dec 21, 2021; 27(47): 8047-8057
Published online Dec 21, 2021. doi: 10.3748/wjg.v27.i47.8047
Orphan patients with inflammatory bowel disease - when we treat beyond evidence
Giuseppe Privitera, Daniela Pugliese, Loris Riccardo Lopetuso, Franco Scaldaferri, Alfredo Papa, Gian Lodovico Rapaccini, Antonio Gasbarrini, Alessandro Armuzzi
Giuseppe Privitera, Alfredo Papa, Gian Lodovico Rapaccini, Antonio Gasbarrini, Alessandro Armuzzi, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Daniela Pugliese, Franco Scaldaferri, Alfredo Papa, Gian Lodovico Rapaccini, Antonio Gasbarrini, Alessandro Armuzzi, CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
Loris Riccardo Lopetuso, CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche , Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome 00168, Italy
Loris Riccardo Lopetuso, Department of Medicine and Ageing Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
Loris Riccardo Lopetuso, Center for Advanced Studies and Technology (CAST), “G.d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
Author contributions: Privitera G, Pugliese D, Scaldaferri F, Lopetuso L, Papa A, Rapaccini GL, Gasbarrini A, and Armuzzi A designed the project; Privitera G wrote the manuscript; Pugliese D, Scaldaferri F, Lopetuso L, Rapaccini GL, Gasbarrini A, and Armuzzi A contributed to literature research and revised critically the manuscript; all authors reviewed and approved the final draft of the article before submission; Armuzzi A oversaw the project and guarantees for the integrity of the work.
Conflict-of-interest statement: The authors declare the following conflicts of interest: Giuseppe Privitera received consultancy fees from Alphasigma and speaker fees from Janssen. Daniela Pugliese received speaker fees and/or advisory board from AbbVie, MSD, Takeda and Janssen, Pfizer. Franco Scaldaferri: advisory board for Abbvie, Janssen, MSD, Sanofi, Takeda. Antonio Gasbarrini reports personal fees for consultancy for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE, and Sanofi S.p.A, personal fees for acting as a speaker for Takeda S.p.A, AbbVie, and Sandoz S.p.A, and personal fees for acting on advisory boards for VSL3 and Eisai. Alessandro Armuzzi: consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Ferring, Gilead, Janssen, Lilly, MSD, Mylan, Pfizer, Samsung Bioepis, Sandoz, Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Biogen, Ferring, Giliead, Janssen, MSD, Mitsubishi-Tanabe, Nikkiso, Pfizer, Sandoz, Samsung Bioepis, Takeda; and research grants from MSD, Pfizer, Takeda. The remaining authors declare no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alessandro Armuzzi, MD, PhD, Professor, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy. alearmuzzi@yahoo.com
Received: March 22, 2021
Peer-review started: March 22, 2021
First decision: June 14, 2021
Revised: July 12, 2021
Accepted: December 8, 2021
Article in press: December 8, 2021
Published online: December 21, 2021
Abstract

Inflammatory bowel disease (IBD) is a chronic condition that requires continuous medical treatment. To date, the medical management of patients with moderately-to-severely active IBD who develop dependence or resistance to corticosteroids is based on immunomodulator drugs. Such therapies are licenced after passing through three phases of randomized controlled trials (RCTs), and are subsequently adopted in clinical practice. However, the real-life population of IBD patients who require these therapies can significantly differ from those included in RCTs. As a matter of fact, there is a number of exclusion criteria – nearly ubiquitous in all RCTs – that prevent the enrolment of specific patients: Chronic refractory pouchitis or isolated proctitis in ulcerative colitis, short-bowel syndrome and stomas in Crohn’s disease, ileorectal anastomosis in both ulcerative colitis and Crohn’s disease, and elderly age are some representative examples. In this frontier article, we aim to give an overview of current literature on this topic, in order to address the main knowledge gaps that need to be filled in the upcoming years.

Keywords: Pouchitis, Proctitis, Stoma, Short-bowel, Ileo-rectal anastomosis, Biologics

Core Tip: Inflammatory bowel disease (IBD) patients with chronic refractory pouchitis, refractory ulcerative proctitis (including those with ileorectal anastomosis), stomas, or short-bowel are routinely excluded from clinical trials, and there is a consequent lack of quality data with regard to their management; however, these patients represent a part of IBD real-life population that needs to be acknowledged. In the present article, our aim is therefore to outline the evidence available so far, and to highlight the main knowledge gaps still present.