Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

Hanauer, Stephen B.; Panaccione, Remo; Danese, Silvio; Cheifetz, Adam S.; Reinisch, Walter; Higgins, Peter; Woodworth, Deborah A.; Zhang, Haiying; Friedman, Gary S.; Lawendy, Nervin; Quirk, Daniel; Nduaka, Chudy I.; Su, Chinyu

doi:10.1016/j.cgh.2018.07.009

Cited by 147 publications

(116 citation statements)

References 17 publications

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“…Outcomes such as efficacy, safety, mode of administration and costs should all be considered before selecting a treatment option for an individual patient. Tofacitinib differs from recently approved biologicals for UC, such as vedolizumab and ustekinumab, with respect to its mode of administration (oral vs intravenous or subcutaneous) and the short induction period with potential rapid clinical response to treatment . In accordance with other treatments, prior failure to biological treatment is an important negative predictor to response.…”

Section: Discussionmentioning

confidence: 99%

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Biemans

Sleutjes

Vries

et al. 2020

Aliment Pharmacol Ther

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Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in | 881 BIEMANS Et Al. How to cite this article: Biemans VBC, Sleutjes JAM, de Vries AC, et al; on behalf of the Dutch Initiative on Crohn and Colitis (ICC). Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry. Aliment Pharmacol Ther. 2020;51:880-888. https://doi.

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Section: Discussionmentioning

confidence: 99%

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Biemans

Sleutjes

Vries

et al. 2020

Aliment Pharmacol Ther

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“…Another important therapeutic target is the Janus kinase (JAK) family of tyrosine kinases, which contains four members JAK1, JAK2, JAK3 and TYK2 that are responsible for mediating signal transduction for many cytokine receptors including interleukins (ILs) 2, 4, 6, 7, 9, 12, 15 and 21 [55]. Tofacitinib is a novel selective inhibitor of JAK1 and JAK3 and, to a lesser extent, JAK2 [56], with Phase 3 trials showing a significant amelioration in symptoms in moderate and severe UC patients [57]. This oral drug works by suppressing the differentiation of pathogenic Th1 and Th17 cells and innate immune cell signalling and it was demonstrated to be efficient in inducing and maintaining remission and achieving mucosal healing in patients with moderately to severely active UC [57].…”

Section: The Role Of Biomarkers and Treatment Options In Ucmentioning

confidence: 99%

Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies

Kaur

Goggolidou

2020

J Inflamm

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Dynamic interactions between the gastrointestinal epithelium and the mucosal immune system normally contribute to ensuring intestinal homeostasis and optimal immunosurveillance, but destabilisation of these interactions in genetically predisposed individuals can lead to the development of chronic inflammatory diseases. Ulcerative colitis is one of the main types of inflammatory diseases that affect the bowel, but its pathogenesis has yet to be completely defined. Several genetic factors and other inflammation-related genes are implicated in mediating the inflammation and development of the disease. Some susceptibility loci associated with increased risk of ulcerative colitis are found to be implicated in mucosal barrier function. Different biomarkers that cause damage to the colonic mucosa can be detected in patients, including perinuclear ANCA, which is also useful in distinguishing ulcerative colitis from other colitides. The choice of treatment for ulcerative colitis depends on disease severity. Therapeutic strategies include anti-tumour necrosis factor alpha (TNF-α) monoclonal antibodies used to block the production of TNF-α that mediates intestinal tract inflammation, an anti-adhesion drug that prevents lymphocyte infiltration from the blood into the inflamed gut, inhibitors of JAK1 and JAK3 that suppress the innate immune cell signalling and interferons α/β which stimulate the production of anti-inflammatory cytokines, as well as faecal microbiota transplantation. Although further research is still required to fully dissect the pathophysiology of ulcerative colitis, understanding its cellular pathology and molecular mechanisms has already proven beneficial and it has got the potential to identify further novel, effective targets for therapy and reduce the burden of this chronic disease.

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“…Tofacitinib is a small-molecule JAK inhibitor that modulates interleukin signaling, blocks the downstream effects of proinflammatory cytokines, and is approved for patients with moderate-severe UC who have failed or cannot tolerate TNF inhibitors. Tofacitinib is an oral medication with a rapid onset of action; clinical response to induction dosing is typically experienced within three days [39]. Depending on disease and patient factors, induction dose ranges from 5 mg twice daily to 10 mg twice daily.…”

Section: Moderate-severe Ulcerative Colitismentioning

confidence: 99%

Ulcerative Colitis: Current and Emerging Treatment Strategies

Kayal

Shah

2019

JCM

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Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis

Cited by 147 publications

References 17 publications

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies

Ulcerative Colitis: Current and Emerging Treatment Strategies

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