Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response DOI Open Access
Duaa Ahmed Elhag, Manoj Kumar,

Marwa Saadaoui

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 6966 - 6966

Published: June 23, 2022

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with highly heterogeneous presentation. It has relapsing and remitting clinical course that necessitates lifelong monitoring treatment. Although availability variety effective therapeutic options including immunomodulators biologics (such as TNF, CAM inhibitors) led to paradigm shift in treatment outcomes management IBD patients, some patients still either fail respond or lose their responsiveness therapy over time. Therefore, according recent Selecting Therapeutic Targets Bowel Disease (STRIDE-II) recommendations, continuous from symptomatic relief endoscopic healing along short- long-term responses are critical for providing tailored algorithm. Moreover, considering high unmet need novel approaches various new modulators cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors cytokines example IL-12/IL-23, IL-22, IL-36, IL-6 anti-adhesion migration strategies β7 integrin, sphingosine 1-phosphate receptors, stem cells), well microbial-based therapeutics decolonize bed buds fecal microbiota transplantation bacterial currently being evaluated different phases controlled trials. This review aims offer comprehensive overview available emerging patients. Furthermore, predictive biomarkers response therapies also discussed.

Language: Английский

Ulcerative colitis DOI
Taku Kobayashi, Britta Siegmund, Catherine Le Berre

et al.

Nature Reviews Disease Primers, Journal Year: 2020, Volume and Issue: 6(1)

Published: Sept. 10, 2020

Language: Английский

Citations

1065
Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy DOI Creative Commons
Adrienne Luoma, Shengbao Suo, Hannah L. Williams

et al.

Cell, Journal Year: 2020, Volume and Issue: 182(3), P. 655 - 671.e22

Published: June 29, 2020

Language: Английский

Citations

378
Design of therapeutic biomaterials to control inflammation DOI Open Access
Zhaoxu Tu, Yiling Zhong, Hanze Hu

et al.

Nature Reviews Materials, Journal Year: 2022, Volume and Issue: 7(7), P. 557 - 574

Published: Feb. 28, 2022

Language: Английский

Citations

316
COVID-19 and immunomodulation in IBD DOI Creative Commons
Markus F. Neurath

Gut, Journal Year: 2020, Volume and Issue: 69(7), P. 1335 - 1342

Published: April 17, 2020

The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome 2. Although COVID-19 leads little or mild flu-like symptoms in the majority of affected patients, disease may cause severe, frequently lethal complications such as progressive pneumonia, distress and organ failure driven hyperinflammation a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In context IBD, several key questions arise. For instance, it important question understand whether patients with IBD (eg, intestinal ACE2 expression) might be particularly susceptible release associated lung injury fatal outcomes. Another highly relevant how deal immunosuppression immunomodulation during affects progress COVID-19. Here, understanding pathophysiology reviewed special reference immune cell activation. Moreover, potential implications these new insights biological therapy are discussed.

Language: Английский

Citations

298
Challenges, Progress, and Prospects of Developing Therapies to Treat Autoimmune Diseases DOI Creative Commons
Lars Fugger, Lise T. Jensen, Jamie Rossjohn

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 63 - 80

Published: April 1, 2020

Language: Английский

Citations

273
Human gut-associated lymphoid tissues (GALT); diversity, structure, and function DOI Creative Commons
Urs Mörbe, Peter B. Jørgensen, Thomas M. Fenton

et al.

Mucosal Immunology, Journal Year: 2021, Volume and Issue: 14(4), P. 793 - 802

Published: March 22, 2021

Language: Английский

Citations

272
Reframing Immune-Mediated Inflammatory Diseases through Signature Cytokine Hubs DOI
Georg Schett, Iain B. McInnes, Markus F. Neurath

et al.

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 385(7), P. 628 - 639

Published: Aug. 11, 2021

The ability to block specific cytokine pathways has revealed pathophysiological differences among autoimmune diseases (e.g., the efficacy of TNF inhibitors in arthritides and inflammatory bowel disorders their inefficacy giant-cell arteritis multiple sclerosis), providing a framework for reclassification.

Language: Английский

Citations

240
The influence of cytokines on the complex pathology of ulcerative colitis DOI Creative Commons
Hiroshi Nakase, Noriko Sato, Naomi Mizuno

et al.

Autoimmunity Reviews, Journal Year: 2021, Volume and Issue: 21(3), P. 103017 - 103017

Published: Dec. 10, 2021

Ulcerative colitis (UC) specifically affects the colon and rectum through multifactorial mechanisms associated with genetic alterations, environmental factors, microbiota, mucosal immune dysregulation. In patients corticosteroid-refractory UC, current therapies primarily employ antibodies against tumor necrosis factor-α, α4β7 integrin, interleukin (IL)-12/23 p40; a small-molecule Janus kinase inhibitor. Despite these revolutionary molecular targeting introduced during last two decades, 30%–55% of fail to respond such agents in induction phase, requiring changes treatment. Here we review basic clinical research aimed address this problem, focusing on pathogenic effects cytokines produced by innate adaptive cells. For example, IL-1β, IL-6, T helper (Th) 1-, Th2-, Th17-associated are expressed at relatively higher levels intestinal tissues UC. However, their expression depend disease stage patient characteristics. The complex pathology UC may induce differences responses therapy. findings studies strongly support argument that future targeted must focus cytokine stages as well distinct profiles individual patients.

Language: Английский

Citations

238
Pathophysiology of Crohn’s disease inflammation and recurrence DOI Creative Commons
Lorenzo Petagna, Amedeo Antonelli, Carlo Ganini

et al.

Biology Direct, Journal Year: 2020, Volume and Issue: 15(1)

Published: Nov. 7, 2020

Abstract Chron’s Disease is a chronic inflammatory intestinal disease, first described at the beginning of last century. The disease characterized by alternation periods flares and remissions influenced complex pathogenesis in which inflammation plays key role. Crohn’s evolution mediated alteration response alterations innate immunity mucosa barrier together with remodeling extracellular matrix through expression metalloproteins increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration sites inflammation, promoting T H 1 response, production cytokines IL-12 TNF-α. itself IL-23 have been targeted for medical treatment CD. Giving limited success therapies, invariably surgical. review will highlight role CD describe surgical approaches prevention almost inevitable recurrence.

Language: Английский

Citations

198
Therapeutic Interleukin-6 Trans-signaling Inhibition by Olamkicept (sgp130Fc) in Patients With Active Inflammatory Bowel Disease DOI Creative Commons
Stefan Schreiber, Konrad Aden,

Joana P. Bernardes

et al.

Gastroenterology, Journal Year: 2021, Volume and Issue: 160(7), P. 2354 - 2366.e11

Published: March 2, 2021

A large unmet therapeutic need exists in inflammatory bowel disease (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the benefit a complete IL6/IL6 receptor (IL6R) blockade is limited by profound immunosuppression. Evidence has emerged that chronic proinflammatory activity IL6 mainly mediated trans-signaling via complex bound soluble IL6R engaging gp130 co-receptor without for membrane-bound IL6R. We have developed decoy protein, sgp130Fc, exclusively blocks and shown efficacy preclinical models IBD, signs immunosuppression.We present 12-week, open-label, prospective phase 2a trial (FUTURE) 16 patients with active IBD treated inhibitor olamkicept (sgp130Fc) assess molecular mechanisms, safety, effectiveness vivo. performed in-depth profiling at various timepoints before after therapy induction identify mechanism action olamkicept.Olamkicept was well tolerated induced clinical response 44% remission 19% patients. Clinical coincided target inhibition (reduction phosphorylated STAT3) marked transcriptional changes inflamed mucosa. An olamkicept-specific signature, distinguishable from signatures anti-tumor necrosis factor (infliximab) or anti-integrin (vedolizumab) therapies identified.Our data suggest holds great promise should undergo full development as new immunoregulatory IBD. (EudraCT no., Nu 2016-000205-36).

Language: Английский

Citations

190