Abstract
Background
Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy.
Aims
We hypothesized that upadacitinib may be effective in treating acute severe colitis.
Methods
A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes.
Results
Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores.
Conclusion
Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.
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Funding
Jordan E. Axelrad receives research support from the Crohn’s and Colitis Foundation, the Judith & Stewart Colton Center for Autoimmunity, and NIH NIDDK K23DK124570.
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All authors have made significant contributions to this manuscript and have approved the final version to be submitted. JC contributed to study conception and design, collection and interpretation of data, and drafting of the manuscript. KKM contributed to study conception and design, collection and interpretation of data, and drafting of the manuscript. SS contributed to study conception and design, collection and interpretation of data, and drafting of the manuscript. PM contributed to study conception and design and drafting of the manuscript. RKC contributed to study conception and design, interpretation of data, and revision of the article for important intellectual content. JEA contributed to collection and interpretation of data and revision of the article for important intellectual content. LG contributed to study conception and design, interpretation of data, and revision of the article for important intellectual content.
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Joseph Clinton, Kiran Motwani, Stephen Schwartz, and Patrick McCarthy have no conflicts of interest to disclose. Lauren George has received income from participation on advisory boards for Bristol Myers Squibb and Janssen. Jordan E. Axelrad has received research grants from BioFire Diagnostics and Genentech and consultancy, advisory board fees, or honorarium from BioFire Diagnostics, Adiso, Abbvie, Pfizer, BMS, and Janssen. Raymond K. Cross has received income from consulting and participation in advisory boards for Abbvie, BMS, Fresenius Kabi, Fzata, Janssen, Magellan Health, Option Care, Pfizer, Samsung bioepis, Sandoz, Sebela, and Takeda, has participated in a Data Safety Monitoring Board for Adiso, is a member of the Executive Committee for the IBD Education group, and is Scientific Co-Director of the CorEvitas registry.
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Clinton, J., Motwani, K.K., Schwartz, S. et al. Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting. Dig Dis Sci 69, 1105–1109 (2024). https://doi.org/10.1007/s10620-024-08302-2
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DOI: https://doi.org/10.1007/s10620-024-08302-2