Ruxolitinib: Targeted Approach for Treatment of Autoinflammatory Very Early Onset Inflammatory Bowel Disease

Rudra, Sharmistha; Shaul, Eliana; Conrad, Máire A.; Patel, Tulsi; Moore, Astrela; Dawany, Noor; Canavan, Megan C.; Sullivan, Kathleen E.; Behrens, Edward M.; Kelsen, Judith R.

doi:10.1016/j.cgh.2021.07.040

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…In addition, ruxolitinib can be administered entirely with sufficient enteral absorption to achieve a clinical response in a cohort with severe intestinal disease. However, this study still has limitations and could not determine whether ruxolitinib will be effective or safe in general use ( 100 ).…”

Section: Therapeutic Methodsmentioning

confidence: 99%

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease

Zhang

Dai

2022

Front. Pediatr.

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Very early onset inflammatory bowel disease (VEO-IBD) is characterized by multifactorial chronic recurrent intestinal inflammation. Compared with elderly patients, those with VEO-IBD have a more serious condition, not responsive to conventional treatments, with a poor prognosis. Recent studies found that genetic and immunologic abnormalities are closely related to VEO-IBD. Intestinal immune homeostasis monogenic defects (IIHMDs) are changed through various mechanisms. Recent studies have also revealed that abnormalities in genes and immune molecular mechanisms are closely related to VEO-IBD. IIHMDs change through various mechanisms. Epigenetic factors can mediate the interaction between the environment and genome, and genetic factors and immune molecules may be involved in the pathogenesis of the environment and gut microbiota. These discoveries will provide new directions and ideas for the treatment of VEO-IBD.

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Section: Therapeutic Methodsmentioning

confidence: 99%

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease

Zhang

Dai

2022

Front. Pediatr.

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“…There is one small study looking at the use of ruxolitinib, a JAK 1/JAK2 specific inhibitor, for patients with AIP VEOIBD. 75 This study found that treatment in a group of six patients decreased diarrhea and fevers rapidly and decreased inflammatory markers, steroid dependance with general endoscopic improvement. Although small this study is encouraging for the use of these medication in this population.…”

Section: Traditional Ibd Therapies In Veoibdmentioning

confidence: 73%

“…The benefit of these medication is that they are oral, they have a rapid onset and do not require evaluation of medication levels. There is one small study looking at the use of ruxolitinib, a JAK 1/JAK2 specific inhibitor, for patients with AIP VEOIBD 75 . This study found that treatment in a group of six patients decreased diarrhea and fevers rapidly and decreased inflammatory markers, steroid dependance with general endoscopic improvement.…”

Section: Treatment Of Veoibdmentioning

confidence: 97%

Understanding very early onset inflammatory bowel disease (VEOIBD) in relation to inborn errors of immunity

Hall,

de Zoeten

2023

Immunological Reviews

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SummaryInflammatory bowel diseases (IBD) are multifactorial diseases which are caused by the combination of genetic predisposition, exposure factors (environmental and dietary), immune status, and dysbiosis. IBD is a disease which presents at any age, ranging from newborns to the elderly. The youngest of the pediatric IBD population have a more unique presentation and clinical course and may have a different etiology. Very early onset IBD (VEOIBD) patients, designated as those diagnosed prior the age of 6, have distinct features which are more frequent in this patient population including increased incidence of monogenetic causes for IBD (0%–33% depending on the study). This proportion is increased in the youngest subsets, which is diagnosed prior to the age of 2. To date, there are approximately 80 monogenic causes of VEOIBD that have been identified and published. Many of these monogenic causes are inborn errors of immunity yet the majority of VEOIBD patients do not have an identifiable genetic cause for their disease. In this review, we will focus on the clinical presentation, evaluation, and monogenic categories which have been associated with VEOIBD including (1) Epithelial cell defects (2) Adaptive immune defects, (3) Innate Immune/Bacterial Clearance and Recognition defects, and (4) Hyperinflammatory and autoinflammatory disorders. We will highlight differential diagnosis of VEOIBD presentations, as well as evaluation and treatment, which will be helpful for those who study and care for VEOIBD patients outside of the pediatric gastroenterology field. This is a fast‐moving field of research which has grown significantly based on knowledge that we gain from our patients. These scientific findings have identified novel mucosal biology pathways and will continue to inform our understanding of gastrointestinal biology.

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“…428 In a single-center retrospective study of patients with inflammatory bowel disease, 6 months of ruxolitinib treatment resulted in improved extraintestinal symptoms, stool frequency, steroid taper, and nutritional status. 429 A case report suggested that the use of ruxolitinib early in the disease courses of refractory systemic idiopathic juvenile arthritis and interstitial lung diseases may block IFN-γ signaling to postpone disease-related deterioration. 430 More recently, the RUXCOVID phase 3 trial randomly divided 432 patients into a ruxolitinib group (n = 287) and a placebo group (n = 145) plus standard of care to estimate the efficacy of ruxolitinib for the treatment of coronavirus disease Evolving cognition of the JAK-STAT signaling pathway: autoimmune.…”

Section: Jak-stat Pathway and Treatmentmentioning

confidence: 99%

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Xue

Yao

et al. 2023

Sig Transduct Target Ther

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The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression. Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases. Currently, drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes: cytokine or receptor antibodies, JAK inhibitors, and STAT inhibitors. And novel agents also continue to be developed and tested in preclinical and clinical studies. The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications. Here, we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway. We also discuss advancements in the understanding of JAK-STAT–related pathogenic mechanisms; targeted JAK-STAT therapies for various diseases, especially immune disorders, and cancers; newly developed JAK inhibitors; and current challenges and directions in the field.

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Ruxolitinib: Targeted Approach for Treatment of Autoinflammatory Very Early Onset Inflammatory Bowel Disease

Cited by 6 publications

References 8 publications

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease

Understanding very early onset inflammatory bowel disease (VEOIBD) in relation to inborn errors of immunity

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

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