Review
Oncology
Juuli Raivola, Teemu Haikarainen, Bobin George Abraham, Olli Silvennoinen
Summary: The JAK/STAT pathway is crucial for immune cell development and function, with mutations linked to hematological diseases like leukemia. Current therapeutic strategies target the pathway's aberrant activation, with FDA-approved JAK inhibitors showing promise in treating autoimmune diseases and blood cancers. However, there is a need for more effective JAK modulators to fully harness their potential in leukemia treatment.
Article
Gastroenterology & Hepatology
Caroline Voskens, Diane Stoica, Marita Rosenberg, Francesco Vitali, Sebastian Zundler, Marion Ganslmayer, Heike Knott, Manuel Wiesinger, Jutta Wunder, Mirko Kummer, Britta Siegmund, Elisabeth Schnoy, Timo Rath, Arndt Hartmann, Holger Hackstein, Beatrice Schuler-Thurner, Carola Berking, Gerold Schuler, Raja Atreya, Markus F. Neurath
Summary: This study reports a successful case of adoptive transfer of ex vivo expanded Tregs in a patient with refractory UC, showing positive responses. These findings suggest that adoptive Treg therapy might be effective in refractory UC.
Article
Gastroenterology & Hepatology
Makoto Naganuma, Taku Kobayashi, Reiko Kunisaki, Katsuyoshi Matsuoka, Shojiro Yamamoto, Ami Kawamoto, Daisuke Saito, Kosaku Nanki, Kazuyuki Narimatsu, Hisashi Shiga, Motohiro Esaki, Shinichiro Yoshioka, Shingo Kato, Masayuki Saruta, Shinji Tanaka, Eriko Yasutomi, Kaoru Yokoyama, Kei Moriya, Yoshikazu Tsuzuki, Makoto Ooi, Mikihiro Fujiya, Atsushi Nakazawa, Takayuki Abe, Tadakazu Hisamatsu, Japanese UC Study Grp
Summary: Most first-use advanced therapies were effective for patients with acute severe ulcerative colitis, while second-use advanced therapies might have had limited benefits in inducing clinical remission. These findings may provide insights for the management of hospitalized patients.
JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Gastroenterology & Hepatology
Mathieu Uzzan, Clement Bresteau, David Laharie, Carmen Stefanescu, Christophe Bellanger, Franck Carbonnel, Melanie Serrero, Stephanie Viennot, Maria Nachury, Aurelien Amiot, Romain Altwegg, Laurence Picon, Stephane Nahon, Lucine Vuitton, Philippe Ah Soune, Julien Kirchgesner, Laurent Peyrin-Biroulet, Yoram Bouhnik
Summary: The study evaluated the effectiveness and safety of tofacitinib as rescue therapy in UC patients hospitalized for flare. Results showed high rates of colectomy-free survival, clinical response, and clinical remission with tofacitinib treatment. Safety profile of tofacitinib was favorable with no deaths observed and only a few adverse events reported. Further validation in controlled trials is needed to confirm the promising potential of tofacitinib in hospitalized UC patients.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Medicine, General & Internal
J. R. Brown, B. Eichhorst, P. Hillmen, W. Jurczak, M. Kazmierczak, N. Lamanna, S. M. O'Brien, C. S. Tam, L. Qiu, K. Zhou, M. Simkovic, J. Mayer, A. Gillespie-Twardy, A. Ferrajoli, P. S. Ganly, R. Weinkove, S. Grosicki, A. Mital, T. Robak, A. Osterborg, H. A. Yimer, T. Salmi, M. -D. -Y. Wang, L. Fu, J. Li, K. Wu, A. Cohen, M. Shadman
Summary: In a multinational phase 3 trial, zanubrutinib was found to be superior to ibrutinib in treating relapsed or refractory CLL or SLL, with better efficacy and fewer side effects.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Aimei Chen, Defang Fang, Yan Ren, Zhiyong Wang
Summary: The study demonstrates that matrine can alleviate DSS-induced intestinal epithelial cell injury by inactivating the JAK2/STAT3 pathway, inhibiting apoptosis and pro-inflammatory factor release.
Review
Gastroenterology & Hepatology
Javier P. Gisbert, Maria Jose Garcia, Maria Chaparro
Summary: For patients with steroid-refractory ASUC, both standard treatment (cyclosporine and infliximab) and newly developed agents (such as vedolizumab and ustekinumab) are effective options.
JOURNAL OF CROHNS & COLITIS
(2023)
Review
Biochemistry & Molecular Biology
Michelle Temby, Theresa L. Boye, Jacqueline Hoang, Ole H. Nielsen, John Gubatan
Summary: This article reviews the role of kinase signaling pathways in colitis-associated colon cancer, including MAPK, CDK, autophagy-activated kinases, JAK-STAT, and other kinases. It also discusses the involvement of JAK-STAT signaling in the pathogenesis of inflammatory bowel disease (IBD) and the potential use of JAK inhibitors for treating IBD.
Article
Medicine, General & Internal
Toshihiko Kakiuchi, Masato Yoshiura
Summary: This study reports the successful use of tofacitinib in treating a pediatric case of moderately active UC. Tofacitinib is a safe drug for pediatric patients with moderately active UC, even in cases refractory to other biologics.
Article
Biotechnology & Applied Microbiology
Hui Li, Ji Xuan, Wei Zhang, Zhentao An, Xinyu Fan, Min Lu, Yaozhou Tian
Summary: The study found that SNHG5 is up-regulated in UC patients and down-regulation can promote proliferation and inhibit apoptosis of YAMC cells, leading to restoration of normal cellular functions through the miR-375/JAK2 axis. This suggests that silencing SNHG5 may be a promising therapeutic approach for UC.
Article
Gastroenterology & Hepatology
Gary R. Lichtenstein, Gerhard Rogler, Matthew A. Ciorba, Chinyu Su, Gary Chan, Ronald D. Pedersen, Nervin Lawendy, Daniel Quirk, Chudy Nduaka, Andrew J. Thorpe, Julian Panes
Summary: Malignancy events in the tofacitinib ulcerative colitis clinical development program were infrequent and rates were comparable to other tofacitinib clinical development programs and biologic UC treatments.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Gastroenterology & Hepatology
David Laharie, Arnaud Bourreille, Julien Branche, Matthieu Allez, Yoram Bouhnik, Jerome Filippi, Frank Zerbib, Guillaume Savoye, Lucine Vuitton, Jacques Moreau, Aurelien Amiot, Laurent Beaugerie, Elena Ricart, Olivier Dewit, Antonio Lopez-Sanroman, Mathurin Fumery, Franck Carbonnel, Anthony Buisson, Benoit Coffin, Xavier Roblin, Gert van Assche, Maria Esteve, Martti Farkkila, Javier P. Gisbert, Philippe Marteau, Stephane Nahon, Martine de Vos, Laurent Peyrin-Biroulet, Jean-Yves Mary
Summary: In patients with steroid-refractory ASUC responding to second-line medical therapy, the process of endoscopic remission started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Immunology
Sunghark Kwon
Summary: JAKs are important enzymes in the JAK-STAT signaling pathway, and dysfunctional JAKs can lead to severe immune system-related diseases. Various JAK inhibitors have been developed to block abnormal JAK-STAT signaling, but drug selectivity and resistance to these inhibitors remain challenges. This review discusses the role and structure of JAKs, as well as strategies for disrupting JAK dimerization to develop novel inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Dermatology
Brett A. King, Brittany G. Craiglow
Summary: JAK inhibitors have revolutionized the treatment of alopecia areata (AA), making it possible to treat moderate-to-severe cases that were previously refractory. This article provides a brief overview of the history of and rationale for JAK inhibitor treatment in AA, discusses phase 3 clinical trial data, and addresses considerations such as differences among JAK inhibitors, safety, and patient selection.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Article
Chemistry, Medicinal
Sean P. Henry, William L. Jorgensen
Summary: The Janus kinases (JAKs) play important roles in the JAK-STAT signaling pathway and are involved in various physiological processes. Although they are targeted by FDA-approved drugs, these drugs often have adverse effects due to their inhibition of JAK kinase activity. However, JAKs have a unique pseudokinase domain (JH2) that regulates the adjacent kinase domain (JH1). Targeting the JH2 domain may provide an alternative approach to modulate JAKs without the associated adverse effects. The recent FDA approval of deucravacitinib, a JH2 ligand, for treating plaque psoriasis demonstrates the potential of this strategy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Gastroenterology & Hepatology
Geert D'Haens, Florian Rieder, Brian G. Feagan, Peter D. R. Higgins, Julian Panes, Christian Maaser, Gerhard Rogler, Mark Lowenberg, Robbert van der Voort, Massimo Pinzani, Laurent Peyrin-Biroulet, Silvio Danese
Review
Gastroenterology & Hepatology
Jeremy Lagrange, Patrick Lacolley, Denis Wahl, Laurent Peyrin-Biroulet, Veronique Regnault
Summary: Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis, with reasons including increased platelet reactivity and continuous coagulation activation. Additionally, fibrinogen levels are increased and fibrin clots are denser in these patients.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
David Laharie, Arnaud Bourreille, Julien Branche, Matthieu Allez, Yoram Bouhnik, Jerome Filippi, Frank Zerbib, Guillaume Savoye, Lucine Vuitton, Jacques Moreau, Aurelien Amiot, Laurent Beaugerie, Elena Ricart, Olivier Dewit, Antonio Lopez-Sanroman, Mathurin Fumery, Franck Carbonnel, Anthony Buisson, Benoit Coffin, Xavier Roblin, Gert van Assche, Maria Esteve, Martti Farkkila, Javier P. Gisbert, Philippe Marteau, Stephane Nahon, Martine de Vos, Laurent Peyrin-Biroulet, Jean-Yves Mary
Summary: In patients with steroid-refractory ASUC responding to second-line medical therapy, the process of endoscopic remission started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
A. Herissay, L. Siproudhis, E. Le Balc'h, A. Merlini L'Heritier, M. Dewitte, T. Wallenhorst, G. Bouguen, C. Brochard
Summary: The medico-surgical strategy for perianal fistulizing Crohn's disease following surgical drainage remains challenging, with a failure rate of 36% at 5 years. Factors associated with failure include surgical technique and the use of immunosuppressants.
COLORECTAL DISEASE
(2021)
Review
Gastroenterology & Hepatology
Walter Reinisch, Krisztina Gecse, Jonas Halfvarson, Peter M. Irving, Jorgen Jahnsen, Laurent Peyrin-Biroulet, Gerhard Rogler, Stefan Schreiber, Silvio Danese
Summary: The introduction of TNF inhibitors has revolutionized the treatment of Crohn's disease, but there are still differences in the actual application of evidence-based guidelines, leading to treatment disparities between countries. The availability of biosimilars can help reduce health inequalities caused by variations in drug availability.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Gastroenterology & Hepatology
Parambir S. Dulai, Laurent Peyrin-Biroulet, Dirk Demuth, Karen Lasch, Kristen A. Hahn, Dirk Lindner, Haridarshan Patel, Vipul Jairath
Summary: Early intervention with vedolizumab may be associated with lower rates of surgery. Use of the clinical decision support tool may help identify patients most likely to benefit from earlier intervention with vedolizumab.
JOURNAL OF CROHNS & COLITIS
(2021)
Review
Gastroenterology & Hepatology
Mariangela Allocca, Federica Furfaro, Gionata Fiorino, Laurent Peyrin-Biroulet, Silvio Danese
Summary: Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. Bowel ultrasound is a non-invasive, well-tolerated, and cost-effective modality for managing IBD patients.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Gastroenterology & Hepatology
Subrata Ghosh, Tom Sensky, Francesc Casellas, Louis-Charles Rioux, Tariq Ahmad, Juan R. Marquez, Tomas Vanasek, Irina Gubonina, Orhan Sezgin, Sandro Ardizzone, Kristina Kligys, Joel Petersson, Yasuo Suzuki, Laurent Peyrin-Biroulet
Summary: The ICONIC study evaluated the burden of ulcerative colitis over a 2-year period using the PRISM tool, showing improvement in disease burden and suffering in patients with early UC. Physicians consistently underestimated disease severity and suffering compared to patients. The PRISM tool correlated with other measures of illness perception, supporting its use as an endpoint reflecting patient suffering.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Gastroenterology & Hepatology
Claire Gouriou, Guillaume Bouguen, Pierre Lahmek, Agnes Pelaquier, Ramuntxo Arotcarena, Armand Garioud, Stephanie De Montigny-Lenhardt, Arnaud Pauwels, David Zanditenas, Claire Charpignon, Remi Combes, Stephane Nahon, Vincent Quentin
Summary: The use of oral anticoagulants does not affect the outcomes of upper gastrointestinal bleeding, with comorbidities and associated treatment being the most important factors worsening the prognosis of UGIB.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Gastroenterology & Hepatology
Charlene Brochard, Marie-Laure Rabilloud, Stephanie Hamonic, Emma Bajeux, Mael Pagenault, Alain Dabadie, Agathe Gerfaud, Jean-Francois Viel, Isabelle Tron, Michel Robaszkiewicz, Jean-Francois Bretagne, Laurent Siproudhis, Guillaume Bouguen
Summary: This study aimed to evaluate the incidence, outcomes, and predictors of perianal Crohn's disease (PCD). The study found that PCD occurred in approximately one-third of patients with CD. Anal ulceration, extraintestinal manifestations, and rectal involvement were associated with the development of fistulizing PCD.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Aurelien Amiot, Guillaume Bouguen, Guillaume Bonnaud, Yoram Bouhnik, Herve Hagege, Laurent Peyrin-Biroulet
Summary: The French treatment algorithms for Crohn's disease (CD) and ulcerative colitis (UC) have been updated, emphasizing anti-TNF as first-line therapy and adding some second-line and selective treatment options. These changes provide up-to-date and easy-to-use guidelines for treating patients with IBD.
DIGESTIVE AND LIVER DISEASE
(2021)
Editorial Material
Gastroenterology & Hepatology
Timothee Wallenhorst, Charlene Brochard, Thomas Lambin, Mael Pagenault, Laurent Siproudhis, Guillaume Bouguen, Mathieu Pioche
Article
Gastroenterology & Hepatology
Sara Tadbiri, Maria Nachury, Yoram Bouhnik, Melanie Serrero, Xavier Hebuterne, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered ABitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Matthieu Allez, Stephanie Viennot, Caroline Trang-Poisson, Nina Dib, Hedia Brixi, Medina Boualit, Laurianne Plastaras, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, David Laharie, Aurelien Amiot, GETAID-IBD-disk Study Group
Summary: In this study, the IBD-disk score was found to be well correlated with IBD daily-life burden, demonstrating its potential for clinical use in assessing IBD-related disability. The high completion rate of the IBD-disk questionnaire suggests that it could be a valuable tool in evaluating the impact of IBD on patients' daily lives. The study also showed that an optimal cut-off of 40 for the IBD-disk score could effectively identify patients with high IBD daily-life burden.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Gastroenterology & Hepatology
Mathilde Laland, Marie Francois, Ferdinando D'Amico, Camille Zallot, Charlene Brochard, Marie Dewitte, Laurent Siproudhis, Laurent Peyrin-Biroulet, Guillaume Bouguen
Summary: Through reviewing medical records, we found that combined medical and surgical management is necessary for the treatment of perianal Crohn's disease (PCD). The best management for PCD patients includes the combination therapy of TNF alpha antagonists with immunosuppressants, seton placement, and additional surgery within 1 year.
COLORECTAL DISEASE
(2022)
Article
Gastroenterology & Hepatology
Nadia Fathallah, Laurent Siproudhis, Melissa Akaffou, Mohamed Amine Haouari, Amandine Landemaine, Elise Pommaret, Lucas Spindler, Charlene Brochard, Guillaume Bouguen, Vincent de Parades
Summary: The clinical and radiological efficacy of darvadstrocel injection in complex perianal fistulas in Crohn's disease was evaluated in this study. The results showed that the treatment resulted in a clinical response for 66.7% of patients and deep remission for 37.2% of patients. A shorter duration of Crohn's disease was associated with deep remission.
COLORECTAL DISEASE
(2023)