Dual biological therapy and small molecules in pediatric inflammatory bowel disease

Francesca Penagini; Luisa Lonoce; Luisa Abbattista; Valentina Silvera; Giulia Rendo; Lucia Cococcioni; Dario Dilillo; Valeria Calcaterra; Gian Vincenzo Zuccotti

doi:10.1016/j.phrs.2023.106935

Dual biological therapy and small molecules in pediatric inflammatory bowel disease

Pharmacol Res. 2023 Oct:196:106935. doi: 10.1016/j.phrs.2023.106935. Epub 2023 Sep 23.

Authors

Francesca Penagini¹, Luisa Lonoce², Luisa Abbattista², Valentina Silvera², Giulia Rendo², Lucia Cococcioni², Dario Dilillo², Valeria Calcaterra³, Gian Vincenzo Zuccotti⁴

Affiliations

¹ Department of Pediatrics, "Vittore Buzzi" Children's Hospital, Milano, Italy. Electronic address: Francesca.penagini@asst-fbf-sacco.it.
² Department of Pediatrics, "Vittore Buzzi" Children's Hospital, Milano, Italy.
³ Department of Pediatrics, "Vittore Buzzi" Children's Hospital, Milano, Italy; Pediatric and Adolescent Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
⁴ Department of Pediatrics, "Vittore Buzzi" Children's Hospital, Milano, Italy; Department of Biomedical and Clinical Science "L. Sacco", University of Milano, Milano, Italy.

PMID: 37748559
DOI: 10.1016/j.phrs.2023.106935

Abstract

Inflammatory bowel diseases (IBDs) including Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U) are chronic inflammatory disorders which can affect the gastrointestinal tract. Anti-tumor necrosis factors antibodies (anti-TNFα) such as infliximab (IFX) and adalimumab (ADA) are the first line biological therapy for severe or complicated IBDs in pediatric age. Second line therapeutic options as vedolizumab (VDZ) and ustekinumab (UST) are currently used off-label in pediatric age. Furthermore, despite optimization of biologics, a great proportion of patients may fail to respond to biologic agents (up to 30%) or lose response over the time (around 50%) hence these patients may be left without another valid therapeutic option. Consequently, several efforts have been made in the last years in order to develop new drugs and to contrive new therapeutic strategies. Small molecule drugs (SMDs) and combination therapy with either two biologic agents or with a SMD and a biological agent have recently been proposed. Data on safety and efficacy of these new therapeutic options are limited. The objective of the present review is to summarize the most up-to-date available literature in pediatric IBD.

Keywords: Dual biological Therapy; Inflammatory Bowel Disease; Pediatric; Small molecules.