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Cited by 111Inflammatory Bowel DiseaseRheumatoid Arthritis Research and TherapiesOcular Diseases and Behçet’s Syndrome

Safety of Janus Kinase Inhibitors in Inflammatory Bowel Diseases

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Núñez, Paulina, Quera, Rodrigo, Yarur, Andres J.·2023·Drugs
DOI 10.1007/s40265-023-01840-5PMC PMC10010235
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Abstract

In recent years, better knowledge of the pathophysiology of inflammatory bowel diseases (IBD) has led to a relevant expansion of the therapeutic arsenal for these conditions. Janus kinase (JAK) inhibitors are a family of small molecules that block one or more of the intracellular tyrosine kinases, including JAK-1, JAK-2, JAK-3 and TYK-2. Tofacitinib, a non-selective small molecule JAK inhibitor, and upadacitinib and filgotinib, which are selective JAK-1 inhibitors, have been approved by the US Food and Drug Administration (FDA) for moderate-to-severe active ulcerative colitis. Compared to biological drugs, JAK inhibitors have a short half-life, rapid onset of action, and no immunogenicity. Both clinical trials and real-world evidence support the use of JAK inhibitors in the treatment of IBD. However, these therapies have been linked with multiple adverse events (AEs) including infection, hypercholesterolemia, venous thromboembolism, major adverse cardiovascular events, and malignancy. While early studies recognized several potential AEs, post-marketing trials have shown that tofacitinib may increase the risk of thromboembolic diseases and major cardiovascular events. The latter are seen in patients aged 50 years or older with cardiovascular risk factors. Hence, the benefits of treatment and risk stratification need to be considered when positioning tofacitinib. Novel JAK inhibitors with a more selective effect on JAK-1 have proven to be effective in both Crohn's disease and ulcerative colitis, offering a potentially safer and efficacious therapeutic option to patients, including those with previous non-response to other therapies such as biologics. Nevertheless, long-term effectiveness and safety data are required.

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  • Clinical trials show that selective JAK1 inhibitors such as filgotinib and upadacitinib are more effective than the pan-JAK inhibitor tofacitinib in treating Crohn's disease and ulcerative colitis.

    “Importantly, evidences from a set of clinical trials showed that the selective JAK1 inhibitors, such as filgotinib and upadacitinib, are more effective than the pan-JAK inhibitor of tofacitinib in the treatment of Crohn’s disease and ulcerative colitis [104–106].”

    From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [106]

    The Abstract and Efficacy sections report that selective JAK1 inhibitors are effective in Crohn’s disease and ulcerative colitis; the Tofacitinib section reports no significant benefit over placebo in Crohn’s disease trials. But the paper also reports tofacitinib’s efficacy in ulcerative colitis and does not establish that filgotinib or upadacitinib is more effective than tofacitinib in either disease. Page numbers were unavailable in our copy. (LLM, conf=0.88)

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Authors
Núñez, P., Quera, R., & Yarur, A. J.
Affiliations
  • Universidad de Los Andes, Chile (CL)
  • Cedars-Sinai Medical Center (US)
Corresponding author
Yarur, Andres J.
ORCID
Venue
Drugs
Publisher
Springer Science and Business Media LLC
Published
2023-03
Volume
83
Issue
4
Pages
299-314
ISSN
  • 0012-6667 (ISSN-L)
  • 1179-1950
DOI
10.1007/s40265-023-01840-5
PMC
PMC10010235
OpenAlex
W4324018025
Cited by
111
References
0
Citations by year
2026: 37 · 2025: 36 · 2024: 35 · 2023: 3
FWCI
4.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Drugs (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders
Cedars-Sinai Medical Library
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords
JAK inhibitors, inflammatory bowel disease, tofacitinib, upadacitinib, filgotinib, ulcerative colitis, Crohn's disease, adverse events, venous thromboembolism, major adverse cardiovascular events, infection risk, hypercholesterolemia, cancer risk, drug safety, risk stratification
MeSH terms
Janus Kinase Inhibitors, Cardiovascular Diseases, Colitis, Ulcerative, Crohn Disease, Humans, Inflammatory Bowel Diseases, Janus Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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