Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence

Ulcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death...

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Main Authors: Raffaele Pellegrino, Giuseppe Imperio, Ilaria De Costanzo, Michele Izzo, Fabio Landa, Assunta Tambaro, Antonietta Gerarda Gravina, Alessandro Federico
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/3/308
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author Raffaele Pellegrino
Giuseppe Imperio
Ilaria De Costanzo
Michele Izzo
Fabio Landa
Assunta Tambaro
Antonietta Gerarda Gravina
Alessandro Federico
author_facet Raffaele Pellegrino
Giuseppe Imperio
Ilaria De Costanzo
Michele Izzo
Fabio Landa
Assunta Tambaro
Antonietta Gerarda Gravina
Alessandro Federico
author_sort Raffaele Pellegrino
collection DOAJ
description Ulcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death. The current therapeutic strategy relies on time-dependent, multi-step algorithms that integrate systemic corticosteroids, calcineurin inhibitors, and biologic agents (specifically infliximab) as medical therapy aimed at avoiding colectomy. Despite this approach, a significant proportion of patients fail to respond to either corticosteroids or infliximab and may require alternative therapeutic options if there is no urgent surgical necessity. These alternatives include other biologics or emerging small molecules, although the evidence supporting these treatments remains extremely low, even considering their well-documented and promising efficacy and safety in moderate-to-severe UC. Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.
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spelling doaj-art-576e3cfacd8a4e24976f552c90bc95012025-08-20T02:42:28ZengMDPI AGPharmaceuticals1424-82472025-02-0118330810.3390/ph18030308Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current EvidenceRaffaele Pellegrino0Giuseppe Imperio1Ilaria De Costanzo2Michele Izzo3Fabio Landa4Assunta Tambaro5Antonietta Gerarda Gravina6Alessandro Federico7Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyHepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, ItalyUlcerative colitis (UC) is an inflammatory bowel disease in which one-quarter of patients are at risk of developing a severe form of the disease known as acute severe UC (ASUC). This condition exposes patients to serious complications, including toxic megacolon, surgical intervention, and even death. The current therapeutic strategy relies on time-dependent, multi-step algorithms that integrate systemic corticosteroids, calcineurin inhibitors, and biologic agents (specifically infliximab) as medical therapy aimed at avoiding colectomy. Despite this approach, a significant proportion of patients fail to respond to either corticosteroids or infliximab and may require alternative therapeutic options if there is no urgent surgical necessity. These alternatives include other biologics or emerging small molecules, although the evidence supporting these treatments remains extremely low, even considering their well-documented and promising efficacy and safety in moderate-to-severe UC. Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.https://www.mdpi.com/1424-8247/18/3/308acute severe ulcerative colitisulcerative colitissmall moleculestofacitinibupadacitinibfilgotinib
spellingShingle Raffaele Pellegrino
Giuseppe Imperio
Ilaria De Costanzo
Michele Izzo
Fabio Landa
Assunta Tambaro
Antonietta Gerarda Gravina
Alessandro Federico
Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence
Pharmaceuticals
acute severe ulcerative colitis
ulcerative colitis
small molecules
tofacitinib
upadacitinib
filgotinib
title Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence
title_full Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence
title_fullStr Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence
title_full_unstemmed Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence
title_short Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence
title_sort small molecules in the treatment of acute severe ulcerative colitis a review of current evidence
topic acute severe ulcerative colitis
ulcerative colitis
small molecules
tofacitinib
upadacitinib
filgotinib
url https://www.mdpi.com/1424-8247/18/3/308
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