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REVIEW article

Front. Gastroenterol.
Sec. Therapy in Gastroenterology
Volume 3 - 2024 | doi: 10.3389/fgstr.2024.1488288
This article is part of the Research Topic Advances in the Treatment of Acute Severe Ulcerative Colitis View all articles

Acute Severe Ulcerative Colitis: Using JAK-STAT inhibitors for improved clinical outcomes

Provisionally accepted
Shruthi Karthikeyan Shruthi Karthikeyan 1Chetan Giri Ambastha Chetan Giri Ambastha 2Kian Keyashian Kian Keyashian 3*
  • 1 School of Medicine, St George's University, St. George's, Grenada
  • 2 Department of Medicine, School of Medicine, Stanford University, Stanford, California, United States
  • 3 Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Stanford University, Stanford, California, United States

The final, formatted version of the article will be published soon.

    Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, whilst exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients.

    Keywords: Acute severe ulcerative colitis (ASUC), Infliximab (ifx), Salvage therapies, JAK inhibitors, Tofacitinib, Upadacitinib

    Received: 29 Aug 2024; Accepted: 29 Oct 2024.

    Copyright: © 2024 Karthikeyan, Ambastha and Keyashian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kian Keyashian, Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, California, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.