Abstract
Background and Aims
Ongoing efforts to break the therapeutic ceiling in inflammatory bowel disease include combination therapy approaches. Dual-targeted therapy (DTT) has been reported in case reports and small case series. This report describes our experience with ustekinumab (UST) and upadacitinib (UPA) as DTT in patients with Crohn’s disease (CD).
Methods
In this retrospective, observational study, we reviewed medical records of patients with CD treated with combined UST and UPA between April 2021 and July 2022. Clinical remission was defined as Harvey–Bradshaw Index (HBI) ≤ 4, and clinical response was defined as decrease in HBI ≥ 3 or physician’s assessment of clinical response.
Results
We identified 10 CD patients treated with UST/UPA, with median follow-up period of 10 months (interquartile range (IQR) 7.3–12). Median age was 35.5 years (IQR 28.3–43.8) and median number of prior biologic treatment exposures was 4 (IQR 4–5). Indications for UST/UPA were active CD (n = 6), extraintestinal manifestations (EIM) (n = 2), and both active CD and EIM (n = 2). Five of six patients with active CD achieved clinical remission with UST/UPA. Two patients with active EIM (joint pain) achieved resolution of their symptoms. One patient exhibited improvement in both conditions. Three patients developed mild respiratory symptoms and one experienced bowel obstruction. Two patients developed nausea resulting in de-escalation of treatment interval or discontinuation altogether.
Conclusion
Based on our case series, combination therapy with UST and UPA may be effective and appears safe in refractory Crohn’s disease and for patients with co-existing extraintestinal manifestations.
Data availability
The data from this analysis are available within the article. Any additional data will be shared by the corresponding author upon reasonable request.
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Concept and design: YM and DTR; data collection: YM and DC; drafting of the manuscript: YM, DC, and DTR; critical revision of the manuscript for important intellectual content: YM, DC, NKC, AZ, and DTR.
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YM has served as a speaker of AbbVie; received research funding from Japan Foundation for Applied Enzymology; and is an endowed chair of AbbVie, JIMRO, Zeria Pharmaceutical, Kyorin Pharmaceutical, Mochida Pharmaceutical, Otsuka Holdings, and EA Pharma. D. Choi has served as a speaker bureau for Janssen Pharmaceuticals and as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Prometheus Laboratory, and Boehringer Ingelheim. XD and JH have no disclosure. DTR has received grant support from Takeda, and has served as a consultant for Abbvie, Altrubio, Allergan Inc., Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim Ltd., Bristol-Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, Glycominds, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, and Techlab Inc.
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This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, with approval from the Institutional Review Board at the University of Chicago.
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Miyatani, Y., Choi, D., Choi, N.K. et al. Dual-Targeted Therapy with Upadacitinib and Ustekinumab in Medically Complex Crohn’s Disease. Dig Dis Sci 69, 355–359 (2024). https://doi.org/10.1007/s10620-023-08182-y
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DOI: https://doi.org/10.1007/s10620-023-08182-y