Agrawal H, Gupta N. Letter to the Editor: Can upadacitinib dose escalation redefine treatment strategies in refractory inflammatory bowel disease? World J Gastrointest Pharmacol Ther 2026; 17(3): 122912 [DOI: 10.4292/wjgpt.122912]
Corresponding Author of This Article
Nikhil Gupta, Department of Surgery, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, BKS Marg, Delhi 110001, India. nikhil_ms26@yahoo.co.in
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Gastroenterology & Hepatology
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letter
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World Journal of Gastrointestinal Pharmacology and Therapeutics
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2150-5349
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Agrawal H, Gupta N. Letter to the Editor: Can upadacitinib dose escalation redefine treatment strategies in refractory inflammatory bowel disease? World J Gastrointest Pharmacol Ther 2026; 17(3): 122912 [DOI: 10.4292/wjgpt.122912]
World J Gastrointest Pharmacol Ther. Sep 5, 2026; 17(3): 122912 Published online Sep 5, 2026. doi: 10.4292/wjgpt.122912
Letter to the Editor: Can upadacitinib dose escalation redefine treatment strategies in refractory inflammatory bowel disease?
Himanshu Agrawal, Nikhil Gupta
Himanshu Agrawal, Department of Surgery, University College of Medical Sciences (University of Delhi), GTB Hospital, Delhi 110095, India
Nikhil Gupta, Department of Surgery, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, Delhi 110001, India
Co-first authors: Himanshu Agrawal and Nikhil Gupta.
Author contributions: Agrawal H conceptualized the manuscript, performed literature review, drafted the manuscript, and critically revised the intellectual content; Gupta N contributed to manuscript design, literature review, scientific interpretation, critical revision of the manuscript, and supervision of the work; Both authors approved the final version of the manuscript and agree to be accountable for all aspects of the work.
AI contribution statement: No AI tools such as ChatGPT, Grammarly, DeepL, or similar platforms were used to generate the scientific content of this manuscript. The authors used ChatGPT (OpenAI) for language refinement, structural reorganization and editing without altering the manuscript’s scientific content, interpretation, or conclusions. All scientific content and interpretation were developed and verified by the authors. No AI tool contributed to the study design, data analysis, or interpretation of results. All intellectual input and scientific decisions were made solely by the authors. No images, figures, or graphical content included in this manuscript were generated using AI.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Corresponding author: Nikhil Gupta, Department of Surgery, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, BKS Marg, Delhi 110001, India. nikhil_ms26@yahoo.co.in
Received: May 8, 2026 Revised: May 18, 2026 Accepted: June 1, 2026 Published online: September 5, 2026 Processing time: 119 Days and 8.7 Hours
Abstract
Despite major advances in inflammatory bowel disease (IBD) therapeutics, secondary loss of response remains a persistent clinical challenge. Upadacitinib, a selective Janus kinase-1 inhibitor, has demonstrated efficacy in both ulcerative colitis and Crohn’s disease; however, real-world patients frequently experience declining response during maintenance therapy. In this editorial, we discuss the findings of Ellington et al, who evaluated upadacitinib dose re-escalation to 45 mg daily in patients with refractory IBD and secondary loss of response. In their retrospective single-center cohort study involving 56 heavily treatment-experienced patients, dose escalation was associated with significant improvement in abdominal pain, hematochezia, urgency, and diarrhea, along with reduced corticosteroid exposure and favorable treatment durability. Objective inflammatory markers and endoscopic outcomes improved numerically but did not achieve statistical significance. These findings highlight the growing importance of individualized therapeutic optimization in IBD management while also underscoring the need for careful patient selection, long-term safety monitoring, and prospective comparative studies. Although current evidence remains preliminary, upadacitinib dose escalation may represent a pragmatic rescue strategy for selected patients with refractory disease.
Core Tip: Upadacitinib dose escalation may provide symptomatic benefit and reduce corticosteroid dependence in selected patients with refractory inflammatory bowel disease who experience secondary loss of response. The findings of Ellington et al support a more flexible and individualized approach to therapeutic optimization while emphasizing the need for careful safety monitoring and prospective validation.
