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World J Gastroenterol. Dec 21, 2022; 28(47): 6743-6751
Published online Dec 21, 2022. doi: 10.3748/wjg.v28.i47.6743
Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease
Domingo Balderramo
Domingo Balderramo, Department of Gastroenterology, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba 5016, Argentina
Author contributions: Balderramo D performed the writing and editing of the manuscript and prepared the figure and table.
Conflict-of-interest statement: Balderramo D reports receiving payment for speaker´s fee from AbbVie, Takeda, and Janssen, and receiving consulting fees from AbbVie, Takeda, Janssen, and Amgen.
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: Domingo Balderramo, MD, PhD, Professor, Department of Gastroenterology, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Naciones Unidas 346, Córdoba 5016, Argentina. dbalderramo@hospitalprivadosa.com.ar
Received: September 22, 2022
Peer-review started: September 22, 2022
First decision: October 18, 2022
Revised: October 26, 2022
Accepted: November 27, 2022
Article in press: November 27, 2022
Published online: December 21, 2022
Processing time: 88 Days and 9.7 Hours
Abstract

Inflammatory bowel disease (IBD) is a group of chronic diseases that includes ulcerative colitis, Crohn’s disease, and indeterminate colitis. Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management. The treatment of patients with IBD is focused on achieving therapeutic goals including clinical, biochemical, and endoscopic variables that result in improvement of the quality of life and prevention of disability. Advanced IBD treatment includes tumor necrosis factor inhibitors, integrin antagonist, antagonist of the p40 subunit of interleukin 12/23, and small molecule drugs. However, despite the multiple treatments available, about 40% of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life, with hospitalization and surgery being necessary in many cases. Dual therapy, a strategy sometimes applicable to refractory IBD patients, includes the combination of two biologics or a biologic in combination with a small molecule drug. There are two distinct scenarios in IBD patients in which this approach can be used: (1) Refractory active luminal disease without extraintestinal manifestations; and (2) patients with IBD in remission, but with active extraintestinal manifestations or immune-mediated inflammatory diseases. This review provides a summary of the results (clinical response and remission) of different combinations of advanced drugs in patients with IBD, both in adults and in the pediatric population. In addition, the safety profile of different combinations of dual therapy is analyzed. The use of newer combinations, including recently approved treatments, the application of new biomarkers and artificial intelligence, and clinical trials to establish effectiveness during long-term follow-up, are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.

Keywords: Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Dual-therapy biologic therapy; Small molecule drugs; Clinical remission

Core Tip: Patients with inflammatory bowel disease (IBD) require prolonged treatment and high utilization of healthcare resources. About 40% of patients are refractory to different treatments with an increase need for hospitalization and surgery. Dual therapy, a strategy applicable to refractory IBD patients, includes the combination of two biologics or a biologic in combination with a small molecule drug. There are two distinct scenarios in IBD therapy in which this approach can be used: (1) Refractory active luminal disease without extraintestinal manifestations; and (2) patients with IBD in remission, but with active extraintestinal manifestations or immune-mediated inflammatory diseases.