Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis

Sandborn, William J.; Ferrante, Marc; Bhandari, Bal R.; Berliba, Elina; Feagan, Brian G.; Hibi, Toshifumi; Tuttle, Jay; Klekotka, Paul; Friedrich, Stuart; Durante, M.; Morgan-Cox, MaryAnn; Laskowski, Janelle; Schmitz, Jochen; D’Haens, Geert R.

doi:10.1053/j.gastro.2019.08.043

Cited by 154 publications

(124 citation statements)

References 33 publications

(48 reference statements)

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“…IL-23, a member of the IL-12 family, is characterized as a proinflammatory cytokine stimulating the production of IL-17 through the differentiation of naïve T cells to T-helper 17 cells (Th17). Interleukin 23 (IL-23) can also stimulate the expression of other IL-17-secreting immune cells expressing the IL-23 receptor (IL-23R), particularly in chronic inflammatory conditions of the intestines, and recently an IL-23 monoclonal antibody has been approved for phase III clinical trials for use in UC [29] although mechanisms leading to the development of chronic inflammatory diseases of the GI tract through the IL-23/Th17 pathway remain elusive [28].…”

Section: Ibd Immune Dysregulationmentioning

confidence: 99%

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

et al. 2020

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The objective of this review is to provide recent evidence for the oral–gut axis connection and to discuss gastrointestinal (GI) immune response, inflammatory bowel disease (IBD) pathogenesis, and potential salivary biomarkers for determining GI health. IBD affects an estimated 1.3% of the US adult population. While genetic predisposition and environment play a role, abnormal immune activity and microbiota dysbiosis within the gastrointestinal tract are also linked in IBD pathogenesis. It has been inferred that a reduced overall richness of bacterial species as well as colonization of opportunistic bacteria induce systemic inflammation in the GI tract. Currently, there is supporting evidence that both oral and gut microbiota may be related to the development of IBD. Despite this, there are currently no curative therapies for IBD, and diagnosis requires samples of blood, stool, and invasive diagnostic imaging techniques. Considering the relative ease of collection, emerging evidence of association with non-oral diseases may imply that saliva microbiome research may have the potential for gut diagnostic or prognostic value. This review demonstrates a link between saliva and intestinal profiles in IBD patients, suggesting that saliva sampling has the potential to serve as a non-invasive biomarker for gut diseases such as IBD in the oral–gut axis.

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Section: Ibd Immune Dysregulationmentioning

confidence: 99%

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

et al. 2020

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“…Ustekinumab, a monoclonal antibody that targets IL-12/IL-23p40, is effective at inducing and sustaining clinical remission in patients with CD, and has shown some evidence of efficacy in UC patients (132). Moreover, IL-23p19 inhibitors including risankizumab, brazikumab, and mirikizumab have been shown to be effective in patients with moderate-to-severe active CD (134,135) or UC (136) in clinical studies. However, the influence of IL-23 blockade on ILC3s remains to be elucidated.…”

Section: Therapeutic Potential Of Ilc3s In Ibdmentioning

confidence: 99%

Metabolic Regulation of Group 3 Innate Lymphoid Cells and Their Role in Inflammatory Bowel Disease

2020

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Inflammatory bowel disease (IBD) is characterized by chronic and relapsing inflammatory disorder of the intestine. IBD is associated with complex pathogenesis, and considerable data suggest that innate lymphoid cells contribute to the development and progression of the condition. Group 3 innate lymphoid cells (ILC3s) not only play a protective role in maintaining intestinal homeostasis and gut barrier function, but also a pathogenic role in intestinal inflammation. ILC3s can sense environmental and host-derived signals and combine these cues to modulate cell expansion, migration and function, and transmit information to the broader immune system. Herein, we review current knowledge of how ILC3s can be regulated by dietary nutrients, microbiota and their metabolites, as well as other metabolites. In addition, we describe the phenotypic and functional alterations of ILC3s in IBD and discuss the therapeutic potential of ILC3s in the treatment of IBD.

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“…Unter Fortführung der Therapie konnte die klinische Remission je nach Dosierungsintervall bis zur Woche 52 in 37-47 % aufrechterhalten werden. Weitere Studien müssen aber offenbar zunächst die Frage der optimalen Dosierung für die Induktionstherapie beantworten [11].…”

Section: Mirikizumabunclassified

Medikamente in der Pipeline

Stallmach

Schmidt

2020

Der Klinikarzt

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ZUSAMMENFASSUNGDurch die Einführung der TNF-Antikörper in die Therapie der chronisch entzündlichen Darmerkrankungen (CED) haben sich die Behandlungsmöglichkeiten revolutioniert. Trotz großer Fortschritte mit der Verfügbarkeit weiterer Antikörper gegen Zytokine oder Zelladhäsionsmoleküle oder Inhibitoren der Januskinasen sind nicht alle Probleme gelöst. Das primäre Nichtansprechen oder Wirkungsverluste zum einen sowie Kontraindikationen, Unverträglichkeiten und Nebenwirkungen zum anderen begründen die Notwendigkeit für die Entwicklung neuer Substanzen; der aktuelle Stand soll hier dargestellt werden. Neben den Wirkungsnachweisen dieser neuen Therapeutika sind direkte Vergleiche zu etablierten Substanzen, sogenannte head-to-head-Studien zu fordern, um der behandelnden Ärztin oder dem Arzt die notwendigen Informationen für einen zielgerichteten und wirkungsvollen Einsatz im Sinne der Patienten zu geben.

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Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis

Cited by 154 publications

References 33 publications

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

Metabolic Regulation of Group 3 Innate Lymphoid Cells and Their Role in Inflammatory Bowel Disease

Medikamente in der Pipeline

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