User's guide to JAK inhibitors in inflammatory bowel disease

Spiewak, Ted; Patel, Anish

doi:10.1016/j.crphar.2022.100096

Cited by 17 publications

(13 citation statements)

References 74 publications

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“…The JAK family members are key drivers of the signaling of multiple proinflammatory cytokines that play a crucial role in AD pathogenesis, i.e., cytokines belonging to the Th2/Th22 pathway, such as IL-4, IL-13, IL-31, TSLP, IL-22, and Th1/Th17 cytokines, of which the foremost include IFN-gamma and IL-17. The same behavior occurs in UC, where the JAK molecules mediate the activity of IL-6, IL-12, IL-23, and IFN-gamma, which are all Th1/17 family members [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Atopic Dermatitis and Ulcerative Colitis Successfully Treated with Upadacitinib

et al. 2023

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Background and Objectives: JAK inhibitors entered current clinical practice as treatment for several immune-related diseases and, recently, for atopic dermatitis. These drugs target the Janus Kinase intracellular cascade, rendering them suitable for treating both Th1 and Th2 immune-mediated responses. Materials and Methods: We report the case of a 36-year-old male patient presenting an overlap of ulcerative colitis, a Th1-related disease, and atopic dermatitis, a Th2-mediated condition. Treatment with upadacitinib was initiated, and laboratory and instrumental follow-ups were carried out for 8 months. Results: The complete and persistent clinical remission of both conditions was observed at a low dose of 15 mg of upadacitinib, even though ulcerative colitis guidelines usually recommend a dosage of 45 mg. No serious adverse responses to therapy were reported. Conclusions: Upadacitinib may be the most suitable management strategy in subjects with coexisting severe conditions mediated by Th1 inflammation, such as ulcerative colitis, and by Th2 cytokines, such as atopic dermatitis.

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Section: Discussionmentioning

confidence: 99%

Atopic Dermatitis and Ulcerative Colitis Successfully Treated with Upadacitinib

et al. 2023

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“…Thus, it is recommended that the adjuvanted recombinant HZ subunit vaccine (Shingrix) be administered intramuscularly in two doses 2 months apart to prevent HZ in patients older than 50. Live vaccines (Zostavax R ) are contraindicated in patients under immunosuppressive therapy, including JAK inhibitors (66,67).…”

Section: Safety and Adverse Effects 41 Infectionsmentioning

confidence: 99%

“…The risk factors that raise the risk of DVT, PE, and ATE are; a previous history of VTE, a hypercoagulable state, reduced mobility, and recent major surgery or trauma. Smoking, MI in the previous 3 months, age higher than 50 years, malignancy, obesity, use of combined oral contraceptives or hormonal replacement therapy, and long flights have also been described (66,67). However, patients with chronic inflammatory diseases, like untreated RA or IBD patients with active disease, may also have a higher risk for venous thrombosis.…”

Section: Venous Thromboembolismmentioning

confidence: 99%

JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases

et al. 2023

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Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract that requires chronic treatment and strict surveillance. Development of new monoclonal antibodies targeting one or a few single cytokines, including anti-tumor necrosis factor agents, anti-IL 12/23 inhibitors, and anti-α4β7 integrin inhibitors, have dominated the pharmacological armamentarium in IBD in the last 20 years. Still, many patients experience incomplete or loss of response or develop serious adverse events and drug discontinuation. Janus kinase (JAK) is key to modulating the signal transduction pathway of several proinflammatory cytokines directly involved in gastrointestinal inflammation and, thus, probably IBD pathogenesis. Targeting the JAK-STAT pathway offers excellent potential for the treatment of IBD. The European Medical Agency has approved three JAK inhibitors for treating adults with moderate to severe Ulcerative Colitis when other treatments, including biological agents, have failed or no longer work or if the patient cannot take them. Although there are currently no approved JAK inhibitors for Crohn’s disease, upadacitinib and filgotinib have shown increased remission rates in these patients. Other JAK inhibitors, including gut-selective molecules, are currently being studied IBD. This review will discuss the JAK-STAT pathway, its implication in the pathogenesis of IBD, and the most recent evidence from clinical trials regarding the use of JAK inhibitors and their safety in IBD patients.

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“…94 JAK inhibitors (as Tofacitinib) are also a promising path in the treatment of IBD, providing an advantage to lacking immunogenicity and showing efficacy in the treatment of moderate to severe UC. 95 Promising results have been shown in both induction and maintenance therapy with IL-23 inhibitors in CD and UC. Clinical and molecular predictors of response should be explored to target the patients who are most likely to benefit from these therapies.…”

Section: Promising Therapeutic Strategiesmentioning

confidence: 99%

A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances

Abdulla¹,

Mohammed²

2022

BTT

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Inflammatory bowel diseases are considered immune disorders with a complex genetic architecture involving constantly changing endogenous and exogenous factors. The rapid evolution of genomic technologies and the emergence of newly discovered molecular actors are compelling the research community to reevaluate the knowledge and molecular processes. The human intestinal tract contains intestinal human microbiota consisting of commensal, pathogenic, and symbiotic strains leading to immune responses that can contribute and lead to both systemic and intestinal disorders including IBD. In this review, we attempted to highlight some updates of the new IBD features related to genomics, microbiota, new emerging therapies and some major established IBD risk factors.

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User's guide to JAK inhibitors in inflammatory bowel disease

Cited by 17 publications

References 74 publications

Atopic Dermatitis and Ulcerative Colitis Successfully Treated with Upadacitinib

Atopic Dermatitis and Ulcerative Colitis Successfully Treated with Upadacitinib

JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases

A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances

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