Skip to main content

Advertisement

Log in

Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting

  • Brief Report
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Lewin S, Velayos FS. Day-by-day management of the inpatient with moderate to severe inflammatory bowel disease. Gastroenterol Hepatol (NY). 2020;16:449–457.

    Google Scholar 

  2. Danese S, Grisham M, Hodge J, Telliez JB. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory cytokines. Am J Physiol Gastrointest Liver Physiol. 2016;310:G155–G162.

    Article  PubMed  Google Scholar 

  3. Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228:273–287. https://doi.org/10.1111/j.1600-065X.2008.00754.x.PMID:19290934;PMCID:PMC2782696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Center for Drug Evaluation and Research. “FDA Approves First Oral Treatment for Moderately to Severely Active CR.” U.S. Food and Drug Administration, FDA, 18 May. 2023, www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-treatment-moderately-severely-active-crohns-disease. Accessed Nov 2, 2023.

  5. “RINVOQ® (Upadacitinib) Receives FDA approval for the treatment of adults with moderately to severely active ulcerative colitis.” News Center, 16 Mar. 2022. news.abbvie.com/news/press-releases/rinvoq-upadacitinib-receives-fda-approval-for-treatment-adults-with-moderately-to-severely-active-ulcerative-colitis.htm. Accessed Nov 2, 2023.

  6. Loftus EV Jr, Colombel JF, Takeuchi K et al. Upadacitinib therapy reduces ulcerative colitis symptoms as early as day 1 of induction treatment. Clin Gastroenterol Hepatol. 2023;21:2347–2358.

    Article  CAS  PubMed  Google Scholar 

  7. Berinstein JA, Sheehan JL, Dias M et al. Tofacitinib for biologic-experienced hospitalized patients with acute severe ulcerative colitis: a retrospective case-control study. Clin Gastroenterol Hepatol. 2021;19:2112–2120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Uzzan M, Bresteau C, Laharie D et al. Tofacitinib as salvage therapy for 55 patients hospitalised with refractory severe ulcerative colitis: a GETAID cohort. Aliment Pharmacol Ther. 2021;54:312–319.

    Article  CAS  PubMed  Google Scholar 

  9. Danese S, Vermeire S, Zhou W et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399:2113–2128.

    Article  CAS  PubMed  Google Scholar 

  10. Seah D, De Cruz P. Review article: the practical management of acute severe ulcerative colitis. Aliment Pharmacol Ther. 2016;43:482–513.

    Article  CAS  PubMed  Google Scholar 

  11. Lewis JD, Chuai S, Nessel L et al. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–1666.

    Article  PubMed  Google Scholar 

  12. Ali NM, Shehab MA. Upadacitinib as a rescue therapy in acute severe ulcerative colitis: A case report and review of the literature. Am J Case Rep. 2023;6:e940966. https://doi.org/10.12659/AJCR.940966.PMID:37926993;PMCID:PMC10640891.

    Article  Google Scholar 

  13. Zinger CH, Ringel Y, Eitan M et al. Upadacitinib for acute severe ulcerative colitis. Inflammatory Bowel Dis 2023;29:1667–1669. https://doi.org/10.1093/ibd/izad180.

    Article  Google Scholar 

  14. Gilmore R, Tan WL, Fernandes R, An Y-K, Begun J. Upadacitinib Salvage therapy for infliximab-experienced patients with acute severe ulcerative colitis. J Crohn’s Colitis. 2023. https://doi.org/10.1093/ecco-jcc/jjad115.

    Article  Google Scholar 

  15. Danese S, Argollo M, Le Berre C, Peyrin-Biroulet L. JAK selectivity for inflammatory bowel disease treatment: Does it clinically matter? Gut. 2019;68:1893–1899.

    Article  CAS  PubMed  Google Scholar 

  16. Harris C, Cummings JRF. JAK1 inhibition and inflammatory bowel disease. Rheumatology (Oxford). 2021;60:ii45–ii51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Joseph Clinton.

Ethics declarations

Competing interest

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Guarantor of the article: Lauren George.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-024-08302-2

Keywords

Navigation