Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn’s Disease: Prospective Real-World Experience

Friedberg, Scott; Choi, David; Hunold, Thomas; Choi, Natalie K.; Garcia, Nicole; Picker, Emma A.; Cohen, Nathaniel A.; Cohen, Russell D.; Dalal, Sushila; Pekow, Joel; Sakuraba, Atsushi; Cleveland, Noa Krugliak; Rubin, David T.

doi:10.1016/j.cgh.2023.03.001

Cited by 32 publications

(24 citation statements)

References 13 publications

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“…Our ndings support those of a recent real-world prospective study that evaluated the e cacy and safety of upadacitinib in Crohn's disease and ulcerative colitis, which found remission rates of 70.6% [14]. With identical de nitions of clinical remission and response, our cohort had a remission rate of 50%.…”

Section: Discussionsupporting

confidence: 87%

“…Our study differs in the fact that we evaluated patients through a complete 12-week induction period and 100% of our patients were on 45mg/day of upadacitinib, while only 82% of patients in Friedberg et al were on 45mg/day. Our population had 92.9% of patients who failed three or more biologics whereas their study had 52.5% of patients who failed three or more biologics [14]. Even though we have a relatively smaller sample size, we can show similar real-world effectiveness and safety in a more treatment-refractory population.…”

Section: Discussionmentioning

confidence: 81%

“…Upadacitinib is a selective inhibitor of janus kinase 1 (JAK1) [13][14][15]. The JAK signalling pathway has been shown to be involved in IBD pathophysiology [5,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…Only four studies have been published evaluating the real-world effects of upadacitinib in Crohn's disease. Some of these studies used suboptimal dosing compared to the phase 3 trial as the medication was used off-label and prior to nal US Food and Drug Administration (FDA) approval [14,[21][22][23]. These studies did not also use the 12-week induction period, having follow-up of 8 weeks or less [14].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Upadacitinib During Induction in Crohn’s disease: Real-World Experience

Jairath,

Zoughlami,

Pilote

et al. 2024

Preprint

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Background Upadacitinib is a selective JAK1 inhibitor that has recently been approved for treatment of moderate-severe Crohn’s disease, with Phase III clinical trials showing positive efficacy and safety profiles. Aim Our aim was to evaluate the real-world experience of upadacitinib in a refractory cohort of Canadian patients with Crohn’s disease. Methods This was a two-centre retrospective study looking at 12-week induction data for patients with active Crohn’s disease from McGill University Health Centre and Hamilton Health Sciences. The primary outcome was clinical remission at 12 weeks, with secondary outcomes including clinical response, biochemical remission, and biochemical response. These parameters were all evaluated at 8 and 12 weeks. Adverse events were summarized for patients who had follow up data available and included in the efficacy analysis. Results There were 28 patients who were treated in total. Five patients discontinued upadacitinib due to no response or side effects. Clinical remission was achieved at 12 weeks in nine patients (9/12, 75%). Clinical response was achieved in nine patients (9/12, 75%), biochemical remission was achieved in five patients (5/13, 38.5%), and biochemical response was achieved in seven patients (7/13, 53.8%). Adverse events were observed in three patients (3/15, 20%), with two having non-serious infections (2/15, 13.3%) and one having fevers of unknown origin (1/15, 6.67%). Conclusion This real-world multicentre Canadian induction study shows favourable efficacy and tolerability of upadacitinib in refractory active Crohn’s disease.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 81%

“…Upadacitinib is a selective inhibitor of janus kinase 1 (JAK1) [13][14][15]. The JAK signalling pathway has been shown to be involved in IBD pathophysiology [5,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Upadacitinib During Induction in Crohn’s disease: Real-World Experience

Jairath,

Zoughlami,

Pilote

et al. 2024

Preprint

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“…Real world experience studies with UPA have demonstrated safety and efficacy in CD, including patients with prior tofacitinib exposure. In addition to clinical response, Friedberg and colleagues looked at biomarker response to UPA, with 64% and 62% of those with elevated levels CRP and Fcal levels, respectively, normalized by week 8 of UPA treatment, although only three patients in this study had isolated ileal disease [19]. One area that needs further understanding and attention in real world practice, is the report of gastrointestinal perforating events that developed in five patients enrolled in clinical trials, four while on UPA 45 mg induction, one while on UPA 30 mg and one on UPA 15 mg maintenance; these perforation occurred in areas of deep ulcers or complications (stricture, obstruction, or fistula) [18 ▪▪ ].…”

Section: Oral Small Moleculesmentioning

confidence: 99%

Biologics, small molecule therapies and surgery in small bowel Crohn's disease

Steinberg,

Chowdhury,

Sharma

et al. 2024

Current Opinion in Gastroenterology

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Purpose of review The terminal ileum and small bowel (SB) are involved in 30–45% of patients with Crohn's disease, while 20% have both small and large bowel involvement. Ileal Crohn's is associated with higher risk of progression to stricturing and penetrating disease1, hence it's imperative to utilize effective therapies to induce and maintain clinical and endoscopic remission and prevent intestinal complications. We review the available data of biologics and upadacitinib in small bowel disease, and the emerging data on the role of surgery as first line therapy for isolated Crohn's ileitis. Recent findings Most trials assessing drug efficacy do not report efficacy by disease location, and robust data on efficacy of therapies in isolated small bowel Crohn's is sparse. Several studies indicate that small bowel disease is generally less responsive to biologics, and could require higher drug trough levels to achieve endoscopic healing. Summary Current therapies for induction and maintenance of remission in moderate to severe Crohn's disease include several classes of monoclonal antibodies and a Janus Kinase inhibitor, upadacitinib. While small bowel Crohn's disease is generally less responsive to treatment, novel agents such as interleukin-23 antagonists and Janus kinase-inhibitors, as well as early ileocecal resection in limited disease have demonstrated efficacy.

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Human intestinal organoids: Modeling gastrointestinal physiology and immunopathology — current applications and limitations

Flood,

Hanrahan,

Nally

et al. 2023

Eur J Immunol

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Human intestinal organoids are an ideal model system to study gastrointestinal physiology and immunopathology. Altered physiology and mucosal immune response are hallmarks of numerous intestinal functional and inflammatory diseases, including inflammatory bowel disease (IBD), coeliac disease, irritable bowel syndrome (IBS), and obesity. These conditions impact the normal epithelial functions of the intestine, such as absorption, barrier function, secretion, and host‐microbiome communication. They are accompanied by characteristic intestinal symptoms and have significant societal, economic, and healthcare burdens. To develop new treatment options, cutting‐edge research is required to investigate their aetiology and pathology. Human intestinal organoids derived from patient tissue recapitulate the key physiological and immunopathological aspects of these conditions, providing a promising platform for elucidating disease mechanisms. This review will summarise recent reports on patient derived human small intestinal and colonic organoids and highlight how these models have been used to study intestinal epithelial functions in the context of inflammation, altered physiology and immune response. Furthermore, it will elaborate on the various organoid systems in use and the techniques/assays currently available to study epithelial functions. Finally, it will conclude by discussing the limitations and future perspectives of organoid technology.This article is protected by copyright. All rights reserved

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Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn’s Disease: Prospective Real-World Experience

Cited by 32 publications

References 13 publications

Efficacy and Safety of Upadacitinib During Induction in Crohn’s disease: Real-World Experience

Efficacy and Safety of Upadacitinib During Induction in Crohn’s disease: Real-World Experience

Biologics, small molecule therapies and surgery in small bowel Crohn's disease

Human intestinal organoids: Modeling gastrointestinal physiology and immunopathology — current applications and limitations

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