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JAK efficacy in Crohn’s disease


Rogler, Gerhard (2020). JAK efficacy in Crohn’s disease. Journal of Crohn's & Colitis, 14(Supplement):S746-S754.

Abstract

Inhibition of Janus kinases in Crohn’s disease (CD) patients has shown conflicting results in clinical trials. Tofacitinib, a pan-JAK inhibitor showed efficacy in ulcerative colitis (UC) and has been approved for the treatment of patients with moderate to severe UC. In contrast, studies in patients suffering from CD were disappointing and the primary endpoint of clinical remission could not be met in the respective phase II induction and maintenance trials. Subsequently, the clinical development of tofacitinib was discontinued in CD. In contrast, efficacy of filgotinib, a selective JAK1 inhibitor, in CD patients was demonstrated in the randomized, double-blinded, placebo-controlled phase II FITZROY study. Upadacitinib also showed promising results in a phase II trial in moderate to severe CD. Subsequently phase III programs in CD have been initiated for both substances, which are still ongoing. Several newer molecules of this class of orally administrated immunosuppressants are tested in clinical programs. The concern of side effects of systemic JAK inhibition is addressed by either exclusively intestinal action or higher selectivity (Tyk2 inhibitors). In general, JAK inhibitors constitute a new promising class of drugs for the treatment of CD.

Abstract

Inhibition of Janus kinases in Crohn’s disease (CD) patients has shown conflicting results in clinical trials. Tofacitinib, a pan-JAK inhibitor showed efficacy in ulcerative colitis (UC) and has been approved for the treatment of patients with moderate to severe UC. In contrast, studies in patients suffering from CD were disappointing and the primary endpoint of clinical remission could not be met in the respective phase II induction and maintenance trials. Subsequently, the clinical development of tofacitinib was discontinued in CD. In contrast, efficacy of filgotinib, a selective JAK1 inhibitor, in CD patients was demonstrated in the randomized, double-blinded, placebo-controlled phase II FITZROY study. Upadacitinib also showed promising results in a phase II trial in moderate to severe CD. Subsequently phase III programs in CD have been initiated for both substances, which are still ongoing. Several newer molecules of this class of orally administrated immunosuppressants are tested in clinical programs. The concern of side effects of systemic JAK inhibition is addressed by either exclusively intestinal action or higher selectivity (Tyk2 inhibitors). In general, JAK inhibitors constitute a new promising class of drugs for the treatment of CD.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Gastroenterology, General Medicine
Language:English
Date:1 August 2020
Deposited On:10 Jan 2020 13:58
Last Modified:01 Oct 2020 15:50
Publisher:Oxford University Press
ISSN:1873-9946
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Crohn's & Colitis following peer review. The definitive publisher-authenticated version is available online at: https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjz186/5645546
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/ecco-jcc/jjz186
PubMed ID:31781755

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