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204. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study

Author

Silvio Danese, Jean-Frederic Colombel, Milan Lukas, Javier P Gisbert, Geert D'Haens, Bu'hussain Hayee, Remo Panaccione, Hyun-Soo Kim, Walter Reinisch, Helen Tyrrell, Young S Oh, Swati Tole, Akiko Chai, Kirsten Chamberlain-James, Meina Tao Tang, Stefan Schreiber, Nazimuddin Aboo, Tariq Ahmad, Xavier Aldeguer Mante, Matthieu Allez, Sven Almer, Romain Altwegg, Montserrat Andreu Garcia, Ramesh Arasaradnam, Sandro Ardizzone, Alessandro Armuzzi, Ian Arnott, Guy Aumais, Irit Avni-Biron, Peter Barrow, Ian Beales, Fernando Bermejo San Jose, Abraham Bezuidenhout, Livia Biancone, Michael Blaeker, Stuart Bloom, Bernd Bokemeyer, Fabrizio Bossa, Peter Bossuyt, Guillaume Bouguen, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Arnaud Bourreille, Christian Boustiere, Tomas Brabec, Stephan Brand, Carsten Buening, Anthony Buisson, Guillaume Cadiot, Xavier Calvet Calvo, Franck Carbonnel, Daniel Carpio, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Nicoleta-Claudia Cimpoeru, Martin Clodi, Gino Roberto Corazza, Rocco Cosintino, Jose Cotter, Thomas Creed, Fraser Cummings, Gian Luigi de' Angelis, Marc De Maeyer, Milind Desai, Etienne Desilets, Pierre Desreumaux, Olivier Dewit, Johanna Dinter, Ecaterina Daniela Dobru, Tomas Douda, Dan Lucian Dumitrascu, Matthias Ebert, Ana Echarri Piudo, Magdy Elkhashab, Chang Soo Eun, Brian Feagan, Roland Fejes, Catarina Fidalgo, Sigal Fishman, Bernard Flourié, Sharyle Fowler, Walter Fries, Csaba Fulop, Mathurin Fumery, Gyula G Kiss, Sonja Gassner, Daniel Gaya, Bastianello Germanà, Liliana Simona Gheorghe, Cyrielle Gilletta de Saint Joseph, Paolo Gionchetti, Adrian-Eugen Goldis, Raquel Gonçalves, Jean-Charles Grimaud, Tibor Gyökeres, Herve Hagege, Andrei Haidar, Heinz Hartmann, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Per Hellström, Pieter Hindryckx, Helena Hlavova, Frank Hoentjen, Stefanie Howaldt, Ludek Hrdlicka, Kyu Chan Huh, Maria Isabel Iborra Colomino, Florentina Ionita-Radu, Peter Irving, Jørgen Jahnsen, ByungIk Jang, Jeroen Jansen, Seong Woo Jeon, Rodrigo Jover Martinez, Pascal Juillerat, Per Karlén, Arthur Kaser, Radan Keil, Deepak Kejariwal, Dan Keret, Reena Khanna, Dongwoo Kim, Duk Hwan Kim, Hyo-Jong Kim, Joo Sung Kim, Kueongok Kim, Kyung-Jo Kim, Sung Kook Kim, Young-Ho Kim, Jochen Klaus, Anna Kohn, Vladimir Kojecky, Ja Seol Koo, Robert Kozak, Milan Kremer, Tunde Kristof, Frederik Kruger, David Laharie, Adi Lahat-zok, Evgeny Landa, Jonghun Lee, Kang-Moon Lee, Kook Lae Lee, YooJin Lee, Frank Lenze, Wee Chian Lim, Jimmy Limdi, James Lindsay, Pilar Lopez Serrano, Edouard Louis, Stefan Lueth, Giovanni Maconi, Fazia Mana, Steven Mann, John Mansfield, Santino Marchi, Marco Marino, John Marshall, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, John McLaughlin, Simon McLaughlin, Ehud Melzer, Jessica Mertens, Paul Mitrut, Tamas Molnar, Vinciane Muls, Pushpakaran Munuswamy, Charles Murray, Timna Naftali, Visvakuren Naidoo, Yusuf Nanabhay, Lucian Negreanu, Augustin Nguyen, Thomas Ochsenkuehn, Ambrogio Orlando, Julian Panes Diaz, Maya Paritsky, Dong Il Park, Jihye Park, Luca Pastorelli, Markus Peck-Radosavljevic, Farhad Peerani, Javier Perez Gisbert, Laurent Peyrin-Biroulet, Laurence Picon, Marieke Pierik, Terry Ponich, Francisco Portela, Maartens Jeroen Prins, Istvan Racz, Khan Fareed Rahman, Jean-Marie Reimund, Max Reinshagen, Xavier Roblin, Rodolfo Rocca, Francesca Rogai, Gerhard Rogler, Agnes Salamon, Ennaliza Salazar, Zoltan Sallo, Sunil Samuel, Miquel de los Santos Sans Cuffi, Edoardo Vincenzo Savarino, Vincenzo Savarino, Guillaume Savoye, Andrada Seicean, Christian Selinger, David Martins Serra, Hang Hock Shim, SungJae Shin, Britta Siegmund, Jesse Siffledeen, Wayne Simmonds, Jan Smid, Jose Sollano, Geun Am Song, Alexander Speight, Ioan Sporea, Dirk Staessen, George Stancu, Alan Steel, David Stepek, Victor Stoica, Andreas Sturm, Gyorgy Szekely, Teck Kiang Tan, Carlos Taxonera Samso, John Thomson, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Marcello Vangeli, Marta Varga, Ana Vieira, Stephanie Viennot, Erica Villa, Petr Vitek, Harald Vogelsang, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Byong Duk Ye, Christopher Ziady, Danese S., Colombel J.-F., Lukas M., Gisbert J.P., D'Haens G., Hayee B., Panaccione R., Kim H.-S., Reinisch W., Tyrrell H., Oh Y.S., Tole S., Chai A., Chamberlain-James K., Tang M.T., Schreiber S., Aboo N., Ahmad T., Aldeguer Mante X., Allez M., Almer S., Altwegg R., Andreu Garcia M., Arasaradnam R., Ardizzone S., Armuzzi A., Arnott I., Aumais G., Avni-Biron I., Barrow P., Beales I., Bermejo San Jose F., Bezuidenhout A., Biancone L., Blaeker M., Bloom S., Bokemeyer B., Bossa F., Bossuyt P., Bouguen G., Bouhnik Y., Bouma G., Bourdages R., Bourreille A., Boustiere C., Brabec T., Brand S., Buening C., Buisson A., Cadiot G., Calvet Calvo X., Carbonnel F., Carpio D., Cheon J.H., Chiba N., Chioncel C., Cimpoeru N.-C., Clodi M., Corazza G.R., Cosintino R., Cotter J., Creed T., Cummings F., de' Angelis G.L., De Maeyer M., Desai M., Desilets E., Desreumaux P., Dewit O., Dinter J., Dobru E.D., Douda T., Dumitrascu D.L., Ebert M., Echarri Piudo A., Elkhashab M., Eun C.S., Feagan B., Fejes R., Fidalgo C., Fishman S., Flourie B., Fowler S., Fries W., Fulop C., Fumery M., G Kiss G., Gassner S., Gaya D., Germana B., Gheorghe L.S., Gilletta de Saint Joseph C., Gionchetti P., Goldis A.-E., Goncalves R., Grimaud J.-C., Gyokeres T., Hagege H., Haidar A., Hartmann H., Hasselblatt P., Hebuterne X., Hellstrom P., Hindryckx P., Hlavova H., Hoentjen F., Howaldt S., Hrdlicka L., Huh K.C., Iborra Colomino M.I., Ionita-Radu F., Irving P., Jahnsen J., Jang B., Jansen J., Jeon S.W., Jover Martinez R., Juillerat P., Karlen P., Kaser A., Keil R., Kejariwal D., Keret D., Khanna R., Kim D., Kim D.H., Kim H.-J., Kim J.S., Kim K., Kim K.-J., Kim S.K., Kim Y.-H., Klaus J., Kohn A., Kojecky V., Koo J.S., Kozak R., Kremer M., Kristof T., Kruger F., Laharie D., Lahat-zok A., Landa E., Lee J., Lee K.-M., Lee K.L., Lee Y., Lenze F., Lim W.C., Limdi J., Lindsay J., Lopez Serrano P., Louis E., Lueth S., Maconi G., Mana F., Mann S., Mansfield J., Marchi S., Marino M., Marshall J., Martin Arranz M.D., Mateescu R.-B., McLaughlin J., McLaughlin S., Melzer E., Mertens J., Mitrut P., Molnar T., Muls V., Munuswamy P., Murray C., Naftali T., Naidoo V., Nanabhay Y., Negreanu L., Nguyen A., Ochsenkuehn T., Orlando A., Panes Diaz J., Paritsky M., Park D.I., Park J., Pastorelli L., Peck-Radosavljevic M., Peerani F., Perez Gisbert J., Peyrin-Biroulet L., Picon L., Pierik M., Ponich T., Portela F., Prins M.J., Racz I., Rahman K.F., Reimund J.-M., Reinshagen M., Roblin X., Rocca R., Rogai F., Rogler G., Salamon A., Salazar E., Sallo Z., Samuel S., Sans Cuffi M.D.L.S., Savarino E.V., Savarino V., Savoye G., Seicean A., Selinger C., Serra D.M., Shim H.H., Shin S., Siegmund B., Siffledeen J., Simmonds W., Smid J., Sollano J., Song G.A., Speight A., Sporea I., Staessen D., Stancu G., Steel A., Stepek D., Stoica V., Sturm A., Szekely G., Tan T.K., Taxonera Samso C., Thomson J., Tichy M., Toth G.T., Tulassay Z., Vangeli M., Varga M., Vieira A., Viennot S., Villa E., Vitek P., Vogelsang H., Vyhnalek P., Wahab P., Walldorf J., Ye B.D., and Ziady C.

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Population, Antibodies, Monoclonal, Humanized, Injections, Subcutaneou, Placebo, Severity of Illness Index, Gastroenterology, Young Adult, Double-Blind Method, Internal medicine, Gastrointestinal Agent, Clinical endpoint, medicine, education, Adverse effect, Aged, Aged, 80 and over, education.field_of_study, Hepatology, business.industry, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Treatment Outcome, Etrolizumab, Concomitant, Colitis, Ulcerative, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Human, medicine.drug
Abstract

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Published
2022
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205. Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial

Author

Laurent Peyrin-Biroulet, Ailsa Hart, Peter Bossuyt, Millie Long, Matthieu Allez, Pascal Juillerat, Alessandro Armuzzi, Edward V Loftus, Elham Ostad-Saffari, Astrid Scalori, Young S Oh, Swati Tole, Akiko Chai, Jennifer Pulley, Stuart Lacey, William J Sandborn, Humberto Aguilar, Tariq Ahmad, Evangelos Akriviadis, Xavier Aldeguer Mante, Istvan Altorjay, Ashwin Ananthakrishnan, Vibeke Andersen, Montserrat Andreu Garcia, Guy Aumais, Irit Avni-Biron, Jeffrey Axler, Kamran Ayub, Filip Baert, Mauro Bafutto, George Bamias, Isaac Bassan, Curtis Baum, Laurent Beaugerie, Brian Behm, Pradeep Bekal, Michael Bennett, Fernando Bermejo San Jose, Charles Bernstein, Dominik Bettenworth, Sudhir Bhaskar, Livia Biancone, Bahri Bilir, Michael Blaeker, Stuart Bloom, Verle Bohman, Francisco Javier Bosques Padilla, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Stephan Brand, Brian Bressler, Markus Brückner, Carsten Buening, Franck Carbonnel, Thomas Caves, Jonathon Chapman, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Dimitrios Christodoulou, Martin Clodi, Albert Cohen, Gino Roberto Corazza, Richard Corlin, Rocco Cosintino, Fraser Cummings, Robin Dalal, Silvio Danese, Marc De Maeyer, Carlos Fernando De Magalhães Francesconi, Aminda De Silva, Henry Debinski, Pierre Desreumaux, Olivier Dewit, Geert D'Haens, Sandra Di Felice Boratto, John Nik Ding, Tyler Dixon, Gerald Dryden, George Aaron Du Vall, Matthias Ebert, Ana Echarri Piudo, Robert Ehehalt, Magdy Elkhashab, Craig Ennis, Jason Etzel, Jan Fallingborg, Brian Feagan, Roland Fejes, Daniel Ferraz de Campos Mazo, Valéria Ferreira de Almeida Borges, Andreas Fischer, Alan Fixelle, Mark Fleisher, Sharyle Fowler, Bradley Freilich, Keith Friedenberg, Walter Fries, Csaba Fulop, Mathurin Fumery, Sergio Fuster, Gyula G Kiss, Santiago Garcia Lopez, Sonja Gassner, Kanwar Gill, Cyrielle Gilletta de Saint Joseph, Philip Ginsburg, Paolo Gionchetti, Eran Goldin, Adrian-Eugen Goldis, Hector Alejandro Gomez Jaramillo, Maciej Gonciarz, Glenn Gordon, Daniel Green, Jean-Charles Grimaud, Rogelio Guajardo Rodriguez, Zoltan Gurzo, Alexandra Gutierrez, Tibor Gyökeres, Ki Baik Hahm, Stephen Hanauer, John Hanson, William Harlan III, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Peter Hendy, Melvin Heyman, Peter Higgins, Raouf Hilal, Pieter Hindryckx, Frank Hoentjen, Peter Hoffmann, Frank Holtkamp-Endemann, Gerald Holtmann, Gyula Horvat, Stefanie Howaldt, Samuel Huber, Ikechukwu Ibegbu, Maria Isabel Iborra Colomino, Peter Irving, Kim Isaacs, Kiran Jagarlamudi, Rajesh Jain, Sender Jankiel Miszputen, Jeroen Jansen, Jennifer Jones, John Karagiannis, Nicholas Karyotakis, Arthur Kaser, Lior Katz, Seymour Katz, Leo Katz, Nirmal Kaur, Edita Kazenaite, Reena Khanna, Sunil Khurana, Joo Sung Kim, Young-Ho Kim, Sung Kook Kim, Dongwoo Kim, Jochen Klaus, Dariusz Kleczkowski, Pavel Kohout, Bartosz Korczowski, Georgios Kouklakis, Ioannis Koutroubakis, Richard Krause, Tunde Kristof, Ian Kronborg, Annette Krummenerl, Limas Kupcinskas, Jorge Laborda Molteni, David Laharie, Adi Lahat-zok, Jonghun Lee, Kang-Moon Lee, Rupert Leong, Henry Levine, Jimmy Limdi, James Lindsay, Nilesh Lodhia, Edward Loftus, Randy Longman, Pilar Lopez Serrano, Edouard Louis, Maria Helena Louzada Pereira, John Lowe, Stefan Lueth, Milan Lukas, Giovanni Maconi, Finlay Macrae, Laszlo Madi-Szabo, Uma Mahadevan-Velayos, Everson Fernando Malluta, Fazia Mana, Peter Mannon, Gerasimos Mantzaris, Ignacio Marin Jimenez, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, Felipe Mazzoleni, Agnieszka Meder, Ehud Melzer, Jessica Mertens, Konstantinos Mimidis, Brent Mitchell, Tamas Molnar, Gregory Moore, Luis Alonso Morales Garza, Reme Mountifield, Vinciane Muls, Charles Murray, Bela Nagy, Markus Neurath, Augustin Nguyen, Remo Panaccione, William Pandak, Julian Panes Diaz, Jihye Park, Luca Pastorelli, Bhaktasharan Patel, Markus Peck-Radosavljevic, Gyula Pecsi, Farhad Peerani, Javier Perez Gisbert, Martin Pesta, Robert Petryka, Raymond Phillips, Marieke Pierik, Vijayalakshmi Pratha, Vlastimil Prochazka, Istvan Racz, Graham Radford-Smith, Daniel Ramos Castañeda, Odery Ramos Júnior, Jaroslaw Regula, Jean-Marie Reimund, Bryan Robbins, Xavier Roblin, Francesca Rogai, Gerhard Rogler, Jerzy Rozciecha, David Rubin, Azalia Yuriria Ruiz Flores, Maciej Rupinski, Grazyna Rydzewska, Sumona Saha, Simone Saibeni, Agnes Salamon, Zoltan Sallo, Bruce Salzberg, Douglas Samuel, Sunil Samuel, William Sandborn, Edoardo Vincenzo Savarino, Anja Schirbel, Robert Schnabel, Stefan Schreiber, John Scott, Shahriar Sedghi, Frank Seibold, Jakob Seidelin, Ursula Seidler, Ahmad Shaban, Ira Shafran, Aasim Sheikh, Alex Sherman, Haim Shirin, Patryk Smolinski, Geun Am Song, Konstantinos Soufleris, Alexander Speight, Dirk Staessen, Andreas Stallmach, Michael Staun, Daniel Stein, Hillary Steinhart, Jonathas Stifft, David Stokesberry, Andreas Sturm, Keith Sultan, Gyorgy Szekely, Kuldeep Tagore, Hugo Tanno, Lena Thin, Syed Thiwan, Carlton Thomas, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Jan Ulbrych, John Valentine, Marta Varga, Eduardo Vasconcellos, Byron Vaughn, Brenda Velasco, Francisco Velazquez, Severine Vermeire, Erica Villa, Aron Vincze, Harald Vogelsang, Miroslava Volfova, Lucine Vuitton, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Mattitiahu Waterman, John Weber, L. Michael Weiss, Anna Wiechowska-Kozlowska, Elise Wiesner, Thomas Witthoeft, Robert Wohlman, Barbara Wozniak-Stolarska, Bruce Yacyshyn, Byong-Duk Ye, Ziad Younes, Lígia Yukie Sassaki, Cyrla Zaltman, Stefan Zeuzem, Neurosurgery, ANS - Neurovascular Disorders, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Peyrin-Biroulet L., Hart A., Bossuyt P., Long M., Allez M., Juillerat P., Armuzzi A., Loftus E.V., Ostad-Saffari E., Scalori A., Oh Y.S., Tole S., Chai A., Pulley J., Lacey S., Sandborn W.J., Aguilar H., Ahmad T., Akriviadis E., Aldeguer Mante X., Altorjay I., Ananthakrishnan A., Andersen V., Andreu Garcia M., Aumais G., Avni-Biron I., Axler J., Ayub K., Baert F., Bafutto M., Bamias G., Bassan I., Baum C., Beaugerie L., Behm B., Bekal P., Bennett M., Bermejo San Jose F., Bernstein C., Bettenworth D., Bhaskar S., Biancone L., Bilir B., Blaeker M., Bloom S., Bohman V., Bosques Padilla F.J., Bouhnik Y., Bouma G., Bourdages R., Brand S., Bressler B., Bruckner M., Buening C., Carbonnel F., Caves T., Chapman J., Cheon J.H., Chiba N., Chioncel C., Christodoulou D., Clodi M., Cohen A., Corazza G.R., Corlin R., Cosintino R., Cummings F., Dalal R., Danese S., De Maeyer M., De Magalhaes Francesconi C.F., De Silva A., Debinski H., Desreumaux P., Dewit O., D'Haens G., Di Felice Boratto S., Ding J.N., Dixon T., Dryden G., Du Vall G.A., Ebert M., Echarri Piudo A., Ehehalt R., Elkhashab M., Ennis C., Etzel J., Fallingborg J., Feagan B., Fejes R., Ferraz de Campos Mazo D., Ferreira de Almeida Borges V., Fischer A., Fixelle A., Fleisher M., Fowler S., Freilich B., Friedenberg K., Fries W., Fulop C., Fumery M., Fuster S., G Kiss G., Garcia Lopez S., Gassner S., Gill K., Gilletta de Saint Joseph C., Ginsburg P., Gionchetti P., Goldin E., Goldis A.-E., Gomez Jaramillo H.A., Gonciarz M., Gordon G., Green D., Grimaud J.-C., Guajardo Rodriguez R., Gurzo Z., Gutierrez A., Gyokeres T., Hahm K.B., Hanauer S., Hanson J., Harlan III W., Hasselblatt P., Hayee B., Hebuterne X., Hendy P., Heyman M., Higgins P., Hilal R., Hindryckx P., Hoentjen F., Hoffmann P., Holtkamp-Endemann F., Holtmann G., Horvat G., Howaldt S., Huber S., Ibegbu I., Iborra Colomino M.I., Irving P., Isaacs K., Jagarlamudi K., Jain R., Jankiel Miszputen S., Jansen J., Jones J., Karagiannis J., Karyotakis N., Kaser A., Katz L., Katz S., Kaur N., Kazenaite E., Khanna R., Khurana S., Kim J.S., Kim Y.-H., Kim S.K., Kim D., Klaus J., Kleczkowski D., Kohout P., Korczowski B., Kouklakis G., Koutroubakis I., Krause R., Kristof T., Kronborg I., Krummenerl A., Kupcinskas L., Laborda Molteni J., Laharie D., Lahat-zok A., Lee J., Lee K.-M., Leong R., Levine H., Limdi J., Lindsay J., Lodhia N., Loftus E., Longman R., Lopez Serrano P., Louis E., Louzada Pereira M.H., Lowe J., Lueth S., Lukas M., Maconi G., Macrae F., Madi-Szabo L., Mahadevan-Velayos U., Malluta E.F., Mana F., Mannon P., Mantzaris G., Marin Jimenez I., Martin Arranz M.D., Mateescu R.-B., Mazzoleni F., Meder A., Melzer E., Mertens J., Mimidis K., Mitchell B., Molnar T., Moore G., Morales Garza L.A., Mountifield R., Muls V., Murray C., Nagy B., Neurath M., Nguyen A., Panaccione R., Pandak W., Panes Diaz J., Park J., Pastorelli L., Patel B., Peck-Radosavljevic M., Pecsi G., Peerani F., Perez Gisbert J., Pesta M., Petryka R., Phillips R., Pierik M., Pratha V., Prochazka V., Racz I., Radford-Smith G., Ramos Castaneda D., Ramos Junior O., Regula J., Reimund J.-M., Robbins B., Roblin X., Rogai F., Rogler G., Rozciecha J., Rubin D., Ruiz Flores A.Y., Rupinski M., Rydzewska G., Saha S., Saibeni S., Salamon A., Sallo Z., Salzberg B., Samuel D., Samuel S., Sandborn W., Savarino E.V., Schirbel A., Schnabel R., Schreiber S., Scott J., Sedghi S., Seibold F., Seidelin J., Seidler U., Shaban A., Shafran I., Sheikh A., Sherman A., Shirin H., Smolinski P., Song G.A., Soufleris K., Speight A., Staessen D., Stallmach A., Staun M., Stein D., Steinhart H., Stifft J., Stokesberry D., Sturm A., Sultan K., Szekely G., Tagore K., Tanno H., Thin L., Thiwan S., Thomas C., Tichy M., Toth G.T., Tulassay Z., Ulbrych J., Valentine J., Varga M., Vasconcellos E., Vaughn B., Velasco B., Velazquez F., Vermeire S., Villa E., Vincze A., Vogelsang H., Volfova M., Vuitton L., Vyhnalek P., Wahab P., Walldorf J., Waterman M., Weber J., Weiss L.M., Wiechowska-Kozlowska A., Wiesner E., Witthoeft T., Wohlman R., Wozniak-Stolarska B., Yacyshyn B., Ye B.-D., Younes Z., Yukie Sassaki L., Zaltman C., and Zeuzem S.

Subjects
Adult, Male, Ulcerative Colitis Flare, medicine.medical_specialty, Asia, Adolescent, Oceania, Population, Antibodies, Monoclonal, Humanized, Injections, Subcutaneou, Placebo, Severity of Illness Index, law.invention, Middle East, Young Adult, Maintenance therapy, Randomized controlled trial, law, Internal medicine, Gastrointestinal Agent, medicine, Adverse effect, education, Aged, Aged, 80 and over, Tumor Necrosis Factor Inhibitor, education.field_of_study, Hepatology, business.industry, Remission Induction, Gastroenterology, Middle Aged, South America, medicine.disease, Ulcerative colitis, Europe, Treatment Outcome, Etrolizumab, North America, Colitis, Ulcerative, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Human
Abstract

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Published
2022

218. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial

Author

Simon Travis, Silvio Danese, Kori Wallace, Xavier Hébuterne, Tomáš Vaňásek, Milan Lukas, Geert R. D'Haens, Gottfried Novacek, Walter Reinisch, Roopal Thakkar, William J. Sandborn, Qian Zhou, Daniel W. Hommes, Paloma Mendez, Jean-Frederic Colombel, Anne M. Robinson, Peter Bossuyt, Remo Panaccione, Ahmet Danalioglu, Paul Rutgeerts, Filip Baert, J Petersson, Ezequiel Neimark, Bidan Huang, Stefan Schreiber, Alessandro Armuzzi, Colombel, Jf, Panaccione, R, Bossuyt, P, Lukas, M, Baert, F, Vanasek, T, Danalioglu, A, Novacek, G, Armuzzi, A, Hebuterne, X, Travis, S, Danese, S, Reinisch, W, Sandborn, Wj, Rutgeerts, P, Hommes, D, Schreiber, S, Neimark, E, Huang, Bd, Zhou, Q, Mendez, P, Petersson, J, Wallace, K, Robinson, Am, Thakkar, Rb, D'Haens, G, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology and Hepatology

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Settore MED/12 - GASTROENTEROLOGIA, a multicentre, randomised, controlled phase 3 trial-, LANCET, cilt.390, ss.2779-2789, 2017 [Colombel J., Panaccione R., Bossuyt P., Lukas M., Baert F., Vanasek T., Danalioglu A., Novacek G., Armuzzi A., Hebuterne X., et al., -Effect of tight control management on Crohn-s disease (CALM)], Inflammatory bowel disease, Severity of Illness Index, law.invention, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Randomized controlled trial, Crohn Disease, law, Internal medicine, Azathioprine, Clinical endpoint, Adalimumab, Medicine, Humans, Glucocorticoids, Aged, Crohn's disease, Intention-to-treat analysis, business.industry, Remission Induction, Disease Management, General Medicine, Middle Aged, medicine.disease, Faecal calprotectin, Surgery, Clinical trial, C-Reactive Protein, Treatment Outcome, N/A, 030220 oncology & carcinogenesis, Antirheumatic Agents, Prednisone, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, business, medicine.drug
Abstract

Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight ( 2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of 200; clinical management group after random assignment: CDAI decrease of

Published
2017

219. Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study

Author

David Laharie, Gilles Bommelaer, Carmen Stefanescu, Silvio Danese, Jacques Moreau, Matthieu Allez, Stéphane Nancey, Romain Altwegg, Anne Bourrier, Jean-Yves Mary, Xavier Roblin, Vered Abitbol, Laurence Picon, Yoram Bouhnik, Guillaume Savoye, Xavier Hébuterne, Laurent Peyrin-Biroulet, Guillaume Bouguen, Edouard Louis, Franck Carbonnel, Magaly Zappa, Maria Nachury, Hedia Brixi, Mathurin Fumery, Arnaud Bourreille, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'hépato-gastro-entérologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de gastro-entérologie et nutrition clinique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Claude Huriez [Lille], Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hépato-Gastro-Onco-Entérologie [CHRU de Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hépato-gastro-entérologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Université de Liège, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hépato-Gastroentérologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), OUERTANI, jeannette, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Bouhnik, Y, Carbonnel, F, Laharie, D, Stefanescu, C, Hebuterne, X, Abitbol, V, Nachury, M, Brixi, H, Bourreille, A, Picon, L, Bourrier, A, Allez, M, Peyrin-Biroulet, L, Moreau, J, Savoye, G, Fumery, M, Nancey, S, Roblin, X, Altwegg, R, Bouguen, G, Bommelaer, G, Danese, S, Louis, E, Mary, Jy, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Lille-CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, medicine.medical_treatment, CROHN'S DISEASE, Disease, 03 medical and health sciences, 0302 clinical medicine, Clinical endpoint, Adalimumab, Medicine, IBD CLINICAL, Crohn's disease, business.industry, Inflammatory Bowel Disease, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bowel resection, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Cohort, ABDOMINAL MRI, 030211 gastroenterology & hepatology, Observational study, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Cohort study, medicine.drug
Abstract

ObjectiveThe efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohn's disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success.DesignWe performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort.ResultsFrom January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion.ConclusionsA successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation.Clinical Trial registration numberNCT01183403; Results.

Published
2017
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220. Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial

Author

Dino Tarabar, Mina Hassan-Zahraee, Michelle Hinz, Silvio Danese, Walter Reinisch, Kenneth J. Gorelick, Vivek Pradhan, Alaa Ahmad, Fabio Cataldi, William J. Sandborn, Miles P. Sparrow, Maria Kłopocka, Clare Robert A, Bruce Salzberg, Xavier Hébuterne, Paul Hellstern, Miloš Greguš, Severine Vermeire, Tomas Vanasek, Joo Sung Kim, Vermeire, S, Sandborn, Wj, Danese, S, Hebuterne, X, Salzberg, Ba, Klopocka, M, Tarabar, D, Vanasek, T, Gregus, M, Hellstern, Pa, Kim, J, Sparrow, Mp, Gorelick, Kj, Hinz, M, Ahmad, A, Pradhan, V, Hassan-Zahraee, M, Clare, R, Cataldi, F, and Reinisch, W

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, Injections, Subcutaneous, Placebo-controlled study, Placebo, Antibodies, Monoclonal, Humanized, Gastroenterology, Severity of Illness Index, Drug Administration Schedule, 03 medical and health sciences, Subcutaneous injection, Young Adult, 0302 clinical medicine, Double-Blind Method, Gastrointestinal Agents, Internal medicine, medicine, Clinical endpoint, Humans, Adverse effect, Aged, Dose-Response Relationship, Drug, business.industry, Tumor Necrosis Factor-alpha, Remission Induction, Absolute risk reduction, General Medicine, Middle Aged, medicine.disease, Ulcerative colitis, Surgery, Clinical trial, 030104 developmental biology, Treatment Outcome, 030211 gastroenterology & hepatology, Colitis, Ulcerative, Female, business
Abstract

Summary Background PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. Methods This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18–65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255. Findings Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (−1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, ten of 71 (14·1%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug. Interpretation PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses. Funding Pfizer.

Published
2016

221. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

Author

Julián Panés, Damián García-Olmo, Gert Van Assche, Jean Frederic Colombel, Walter Reinisch, Daniel C. Baumgart, Axel Dignass, Maria Nachury, Marc Ferrante, Lili Kazemi-Shirazi, Jean C. Grimaud, Fernando de la Portilla, Eran Goldin, Marie Paule Richard, Mary Carmen Diez, Ignacio Tagarro, Anne Leselbaum, Silvio Danese, Jean F. Colombel, Anton Stift, Jörg Tschmelitsch, Karl Mrak, Herbert Tilg, Irmgard Kroberger, André D’Hoore, Danny De Looze, Filip Baert, Paul Pattyn, Philippe Zerbib, Frank Zerbib, Stéphanie Viennot, Jean-Louis Dupas, Pierre-Charles Orsoni, Xavier Hebuterne, Amine Rahili, Matthieu Allez, Yves Panis, Max Reinshagen, Roland Scherer, Andreas Sturm, Wolfgang Kruis, Daniel-Simon Duek, Matti Waterman, Adi Lahat-Zok, Oded Zmora, Hagit Tulchinsky, Yair Edden, Antonino Spinelli, Vito Annese, Imerio Angriman, Gabriele Riegler, Francesco Selvaggi, Bas Oldenburg, Lennard Gilissen, Gust Van Montfort, Mark Lowenberg, Adrianus Willem Bemelman, Raúl Almenara, María Dolores Martín Arranz, Mariano García-Arranz, Javier Pérez Gisbert, Rosana Palasí, Carlos Taxonera Samsó, Jose Manuel Herrera Justiniano, Ricardo Rada, Mª Teresa Butrón, Daniel Carpio López, Antonio López-Sanromán, Joaquín Hinojosa de Val, Amparo Solana, F. Xavier González Argenté, Carlos Pastor, Hector Guadalajara, Panes, J, Garcia-Olmo, D, Van Assche, G, Colombel, Jf, Reinisch, W, Baumgart, Dc, Dignass, A, Nachury, M, Ferrante, M, Kazemi-Shirazi, L, Grimaud, Jc, de la Portilla, F, Goldin, E, Richard, Mp, Diez, Mc, Tagarro, I, Leselbaum, A, Danese, S, Panes, J., Garcia-Olmo, D., Van Assche, G., Colombel, J. F., Reinisch, W., Baumgart, D. C., Dignass, A., Nachury, M., Ferrante, M., Kazemi-Shirazi, L., Grimaud, J. C., de la Portilla, F., Goldin, E., Richard, M. P., Diez, M. C., Tagarro, I., Leselbaum, A., Danese, S., Stift, A., Tschmelitsch, J., Mrak, K., Tilg, H., Kroberger, I., D'Hoore, A., De Looze, D., Baert, F., Pattyn, P., Zerbib, P., Zerbib, F., Viennot, S., Dupas, J. -L., Orsoni, P. -C., Hebuterne, X., Rahili, A., Allez, M., Panis, Y., Reinshagen, M., Scherer, R., Sturm, A., Kruis, W., Duek, D. -S., Waterman, M., Lahat-Zok, A., Zmora, O., Tulchinsky, H., Edden, Y., Spinelli, A., Annese, V., Angriman, I., Riegler, G., Selvaggi, F., Oldenburg, B., Gilissen, L., Van Montfort, G., Lowenberg, M., Bemelman, A. W., Almenara, R., Martin Arranz, M. D., Garcia-Arranz, M., Perez Gisbert, J., Palasi, R., Samso, C. T., Herrera Justiniano, J. M., Rada, R., Butron, M. T., Lopez, D. C., Lopez-Sanroman, A., Hinojosa de Val, J., Solana, A., Gonzalez Argente, F. X., Pastore, Concetta, Guadalajara, H., Gastroenterology and Hepatology, and AGEM - Digestive immunity

Subjects
Male, Time Factors, Intention to Treat Analysi, medicine.medical_treatment, Gastroenterology, 0302 clinical medicine, Crohn Disease, Risk Factors, Clinical endpoint, Israel, Transplantation, Homologou, Crohn's disease, education.field_of_study, medicine.diagnostic_test, Remission Induction, Stem-cell therapy, Magnetic Resonance Imaging, Intention to Treat Analysis, Europe, Treatment Outcome, Adipose Tissue, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Clinical Remission, Human, Adult, Homologous, medicine.medical_specialty, Time Factor, Population, Placebo, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Transplantation, Homologous, Humans, Rectal Fistula, education, Adverse effect, Transplantation, Intention-to-treat analysis, Hepatology, business.industry, Risk Factor, Cell Therapy, Magnetic resonance imaging, Anal Fistula, Combined Remission, Stem Cell Transplantation, medicine.disease, business
Abstract

Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

Published
2018
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222. Management of intestinal failure in Europe. A questionnaire based study on the incidence and management

Author

Jonathan Shaffer, P. Thul, Xavier Hébuterne, F. Bozzetti, A. Micklewright, Michael Staun, José Moreno, Kent V. Haderslev, Marek Pertkiewicz, Loris Pironi, Staun, M., Hebuterne, X., Shaffer, J., Haderslev, K. V., Bozzetti, F., Pertkiewicz, M., Micklewright, A., Moreno, J., Thul, P., and Pironi, Loris

Subjects
Pediatrics, medicine.medical_specialty, Referral, Sports medicine, Physiology, business.industry, Research, Incidence (epidemiology), Human physiology, Bioinformatics, INTESTINAL FAILURE, Enteral administration, HOME PARENTERAL NUTRITION, Intestinal failure, Treatment practice, MANAGEMENT, Medicine, Orthopedics and Sports Medicine, Lost to follow-up, business
Abstract

Background Intestinal failure is the outcome of a number of gastrointestinal diseases and characterized by significant reduction in functional gut mass. If not resolved patients often face long-term nutritional support. This study gathered information about how patients referred with intestinal failure are managed in specialised European centres. Methods A questionnaire was circulated in 7 European countries via representatives of the ESPEN-HAN working group to seek information about experience in treating patients with intestinal failure. We asked about clinical outcome, information about structure and organisation of the department, referral criteria, treatment procedures and guidelines. Results 17 centres in 6 European countries completed the questionnaire: UK, n = 6, France, n = 4, Spain, n = 3, Denmark, n = 2, Italy, n = 1, Poland, n = 1. The experience of the centres in treating patients was in the range 12–30 years. The total number of patients on HPN in all centres was 590. The number of patients referred to centres with intestinal failure during the period January to December 2000 was n = 882: UK, n = 375 (range 2–175), France, n = 308 (range 24–182), Italy and Spain, n = 43 (range 9–52), Denmark n = 51 (range 14–37), the centre in Poland included 53 patients. Comparing all centres the following distribution among patients (median % (range%)) with regard to the endpoints were reported: Oral nutrition 32% (23–50%), enteral/tube feeding 11% (4–23%), HPN 36% (15–57%), lost to follow up 10% (0–35%), dead 9% (5–18%). No patients had an intestinal transplant. Conclusion The study provides information about how patients with intestinal failure are managed across Europe and the data indicates that treatment practice varies between countries.

Published
2007
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223. Candidates for intestinal transplantation: a multicenter survey in Europe

Author

André Van Gossum, Michael Staun, Alastair Forbes, Olivier Goulet, Virginie Colomb, Loris Pironi, Bernard Messing, Federico Bozzetti, P. Thul, Malgorzata Lyszkowska, Xavier Hébuterne, José Manuel Moreno Villares, A. Micklewright, Pironi, Lori, Hebuterne, X., Van Gossum, A., Messing, B., Lyszkowska, M., Colomb, V., Forbes, A., Micklewright, A., Villares, J. M., Thul, P., Bozzetti, F., Goulet, O., and Staun, M.

Subjects
Adult, Male, INTESTINAL TRANSPLANTATION, Parenteral Nutrition, medicine.medical_specialty, Pediatrics, Adolescent, Referral, Attitude of Health Personnel, MEDLINE, Surveys and Questionnaires, Epidemiology, Humans, Medicine, EPIDEMIOLOGY, Child, Referral and Consultation, Aged, Aged, 80 and over, Hepatology, business.industry, Patient Selection, Gastroenterology, Infant, Middle Aged, Chronic intestinal failure, Surgery, Europe, Intestines, Transplantation, Parenteral nutrition, HOME PARENTERAL NUTRITION, Child, Preschool, Multicenter survey, Candidacy, Female, business, CHRONIC INTESTINAL FAILURE
Abstract

OBJECTIVES: Epidemiology of candidacy for intestinal transplantation (ITx) and timing for referral for ITx are unknown. Patient candidacy and physician attitudes toward ITx were investigated among centers that participated in previous European surveys on home parenteral nutrition (HPN). METHODS: Patients on HPN for benign intestinal failure (IF) were evaluated by a structured questionnaire. Candidacy was assessed by USA Medicare and American Transplantation Society criteria, categorized as: (1) life-threatening HPN complications; (2) high risk of death because of the gastrointestinal disease; (3) IF with high morbidity or patient HPN refusal. Physicians judged candidacy as immediate or potential. RESULTS: Forty-one centers from nine countries enrolled 688 adults (> 18 yr) and 166 pediatric patients; 70% of patients were from five countries which collected 60-100% of their HPN patients. Candidacy was 15.7% in adults and 34.3% in pediatrics (HPN failure, 62.1% and 28.1%; gastrointestinal disease, 25.9% and 59.6%; high morbidity IF or HPN refusal, 12.0% and 12.3%, respectively). Immediate candidacy was required for 14.8% of adult and 15.8% of pediatric candidates (< 50% of candidates because of HPN-related liver failure). Among centers, the candidacy rate ranged 0-100% and was negatively associated with the number of patients enrolled in the survey (R = -0.463, p = 0.002). Among the major contributing countries, candidacy ranged 0.3-0.8/million inhabitants for adults and 0.9-2/million inhabitants < or = 18 yr for pediatric candidates. CONCLUSIONS: The rate of candidacy and the indications for ITx candidacy differed greatly among age groups and HPN centers; within countries candidacy was more homogeneous; physicians had a generally reserved attitude toward ITx.

Published
2006

224. Monitoring of patients on home parenteral nutrition (HPN) in Europe: a questionnaire based study on monitoring practice in 42 centres

Author

A. Wengler, A. Micklewright, André Van Gossum, Loris Pironi, Michael Staun, Federico Bozzetti, P. Thul, Marek Pertkiewicz, Xavier Hébuterne, José Moreno, Wengler, A., Micklewright, A., Hebuterne, X., Bozzetti, F., Pertkiewicz, M., Moreno, J., Pironi, Lori, Thul, P., Van Gossum, A., and Staun, M.

Subjects
medicine.medical_specialty, Pediatrics, CLINICAL PRACTICE, Time Factors, EUROPEAN COUNTRY, Critical Care and Intensive Care Medicine, Primary disease, Quality of life, Neoplasms, Surveys and Questionnaires, medicine, Humans, Monitoring, Physiologic, Nutrition and Dietetics, Adult patients, business.industry, Public health, Community nurse, After discharge, Home Care Services, Europe, Intestinal Diseases, Parenteral nutrition, Home visits, Treatment Outcome, HOME PARENTERAL NUTRITION, Family medicine, Health Care Surveys, Practice Guidelines as Topic, Quality of Life, business, Parenteral Nutrition, Home
Abstract

Summary Introduction & aim To gather information about how adult patients on home parenteral nutrition (HPN) are monitored after discharge from the hospital. Method A questionnaire about HPN monitoring practice was circulated to HPN centres in eight European countries through the representative of the ESPEN 1 HAN-working group 2 . Centres were asked about guidelines, home visits and how monitoring and handling of complications were managed. Results Fourty-two centres in eight European countries completed the questionnaire: UK n = 14 , France n = 9 , Belgium n = 4 , Italy n = 4 , Poland n = 4 , Denmark n = 4 , Spain n = 2 , Germany n = 1 . The HPN experience of the centres was in the range 2–30 years. Centres ranged in size from 0 to 125 HPN patients representing a total number of 934 of whom 54% had received HPN for more than 2 years. The primary disease was non-malignant in 90% whilst 10% had been diagnosed with active cancer. Of the centres 92% had a HPN team and 66% had written guidelines for monitoring HPN. Home visits after discharge for monitoring purposes were carried out by 31 of the centres involving the HPN team, general practitioner, community nurse or home care agency. Stable patients on HPN for more than 12 months were monitored at the discharging hospital (73%), at a local hospital (12%), by the General Practitioner (11%) or by a home care agency (4%). Of the centres, 90% reported that the main responsibility for monitoring was assigned to a specific person. The intervals between monitoring visits for the stable HPN patient was in the range 1–6 months, 52% of the centres reported intervals of 2–3 months. In case of complications 76% of centres reported that patients got in touch with the HPN team, 2% the local hospital, 5% the home care agency, and 17% other. Re-admission to hospital was usually to the HPN centre and only occasionally to a local hospital. Conclusion In Europe a specialised team at the discharging hospital monitors HPN patients and 66% of the centres had some kind of written guidelines.

Published
2006

225. P262: Évaluation du caractère prédictif de l’échelle visuelle analogique (EVA) pour la détermination des ingesta des malades atteints d’un cancer.

Author

Galmiche, M., Besnard, I., Palomba, K., Eyraud, E., Frin, A.-C., Ouvrier, D., Piche, T., Schneider, S.M., and Hebuterne, X.

Abstract

Introduction et but de l’étude La prise en charge nutritionnelle précoce est de plus en plus préconisée chez les malades atteints de cancer. Les recommandations de pratique clinique (RPC) de la SFNEP recommandent une évaluation des ingesta à l’aide d’une échelle visuelle analogique (EVA), pour tous les malades, dès la consultation d’annonce et avant toute prise en charge thérapeutique (1). Les RPC recommandent également une prise en charge des malades chez qui l’EVA initiale est < 7 (patients dont les ingesta sont supposés être < 70 % des besoins énergétiques). Le but de cette étude a été d’évaluer : 1 – la fiabilité de l’EVA pour l’estimation des ingesta des malades atteints de cancer ; 2 – la pertinence du seuil d’EVA < 7/10 pour la prise en charge recommandé par les RCP. Matériel et méthodes Il s’agit dune étude prospective visant à évaluer les ingesta de tous les malades consécutifs vus pour la première fois pendant six mois dans une unité d’oncologie médicale. Lors de la consultation d’annonce, une fiche de recueil alimentaire était remise aux malades et le calcul des ingesta réels était réalisé sur trois jours à l’aide du logiciel Bilnut. Les malades évaluaient ensuite leurs ingesta sur une EVA graduée de 0 à 10. Afin de déterminer si les besoins énergétiques étaient couverts, les apports énergétiques calculés étaient comparés aux besoins théoriques chez les malades atteints de cancer fixés par les RCP (35 kcal/kg/j) ; les apports calculés étaient exprimés en pourcentage des apports théoriques. Les résultats de l’EVA ont ensuite été comparés aux ingesta réels à l’aide d’un test de Bland et Altman et d’un test rho de Spearman. L’évaluation de la valeur seuil de l’EVA qui permettait de déterminer avec la plus grande précision les malades chez qui les ingesta étaient inférieurs à 70 % des apports théoriques a été réalisée à l’aide des calculs des seuils de sensibilité, spécificité, valeurs prédictives positives et valeurs prédictives négatives ainsi que par les courbes ROC. Résultats et Analyse statistique 189 malades consécutifs ont été vus entre le 1er décembre 2013 et le 31 mai 2014 ; 125 ont finalement été inclus dans l’étude. Les malades non étudiés l’étaient en raison d’un refus de participer (n = 33), d’un problème de langage (n = 16), d’une nutrition artificielle (n = 11) ou de causes diverses (n = 4). Sur les 125 malades inclus, huit n’ont pas ramené un relevé d’ingesta évaluable, ainsi 117 ont fait l’objet de cette étude. Il s’agissait de 48 femmes et de 69 hommes, d’âge moyen 65,5 ± 11,1 ans, souffrant d’un cancer colo-rectal (36 %), du foie ou des voies biliaires (18 %), du pancréas (18 %), de l’ovaire (8 %) ou autre (20 %). L’IMC moyen était à 25,6 ± 4,8 et 19 % des patients étaient dénutris selon les critères de perte de poids > 5 % en un mois ou 10 % en six mois et/ou IMC < 18,5 ou 21 pour les patients de plus de 70 ans. L’EVA moyenne était à 8,1 ± 2,1 et les ingesta à 1971 ± 655 kcal/jour (27,8 ± 10,4 kcal/kg/j). Les graphiques de Bland et Altman [moyenne des différences (biais) = −4,4 %, limites de concordance à 95 % :] −60 ; 51 [et limite d’acceptabilité > 20 %] et le test rho de Spearman (p = 0,3, P = 0,001) [ABSTRACT FROM AUTHOR]

Published
2014
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226. O08: Influence de la concentration des compléments nutritionnels oraux sur leur observance et les apports protéino-énergétiques des patients hospitalisés : résultats d’une étude randomisée en cluster.

Author

Galmiche, M., Alessandrini, E., Eyrault, E., Kotovtchikhine, A., Palomba, K., Dorigny, B., Schneider, S.M., Darmon, P., and Hebuterne, X.

Abstract

Introduction et but de l’étude Chez les malades hospitalisés, les compléments nutritionnels oraux (CNO) permettent un gain de poids et réduisent la morbidité et la mortalité (1). Cependant, l’observance des CNO est le principal facteur limitant leur efficacité ; elle dépend des patients, de leur pathologie, des périodes de jeûne imposées par les examens complémentaires, de la manière dont les CNO sont proposés aux malades, mais aussi de leur palata-bilité et de leur volume. Des nouveaux CNO hyper-concentrés qui permettent d’apporter la même quantité d’énergie sous un volume plus faible sont désormais disponibles. Le but de cette étude était de comparer la consommation de deux CNO iso-énergétiques mais de volume différent : un complément très concentré (CTC : 125 mL, 2,4 kcal/mL) apportant 300 kcal et 18 g de protéines par unité (Fortimel Compact Protein ® , Nutricia Nutrition clinique) et un complément concentré (CC : 200 mL, 1,5 kcal/mL) apportant 300 kcal et 20 g de protéines par unité (Fortimel Extra ® , Nutricia Nutrition Clinique). Matériel et méthodes Il s’agit d’une étude prospective randomisée, croisée de type cluster réalisée dans quatre unités médicales (A, B, C, D) de deux centres hospitalo-universitaires. Le premier mois de l’étude tous les malades des unités A et B du premier établissement recevaient des CTC et ceux des unités C et D du second établissement des CC. L’inverse était réalisé au cours de la seconde période d’un mois. Les deux périodes étaient séparées d’un intervalle de deux semaines et aucun malade n’a participé aux deux périodes de l’étude. Le nombre de CNO proposé aux malades était laissé à l’appréciation des équipes soignantes des unités mais tous les malades recevaient au moins 2 CNO par jour. Au cours de la journée, aucune incitation particulière à la consommation des CNO n’était proposée aux malades. La consommation de chaque CNO a été évaluée quotidiennement à l’aide de la méthode des pesées et globalisée à l’ensemble des malades. Les résultats sont exprimés en moyennes ± DS et les comparaisons ont été réalisées à l’aide de teste non paramétriques de Mann-Whitney. Résultats et Analyse statistique Au total, 97 malades ont participé à l’étude. Dans le groupe CC, il s’agissait de 23 femmes et 25 hommes ; dans le groupe CTC de 25 femmes et 24 hommes. L’âge (69,7 ± 17,9 vs70,6 ± 19,5 ans), la maladie sous-jacente (cancers 20 % vs 19 %; pathologies digestives : 49 % vs 48 %; pathologies cardio-vasculaires : 9% vs 12%; autres affections 22% vs 21%), l’IMC (20,4 ±4 vs 20,4 ± 4) et la perte de poids (9,1 ± 6,8 % vs 12,6 ± 8,7 %) n’étaient pas significativement différentes dans les deux groupes. 606 CNO ont été proposés pendant les périodes CT vs 746 (P < 0,0001) pendant les périodes CTC. La durée moyenne d’administration des CNO était identique dans les deux groupes (6,6 ± 6,0 vs 7,2 ± 5,3 jours) mais le nombre de CNO distribué par malade était plus important avec les CTC comparativement aux CT (2,5 ± 0,8 vs 2,0 ± 0,5 ; P < 0,001). La consommation moyenne par unité distribuée était par contre identique pour les CTC et les CT : 64,5 ± 36,0 % vs 65,5 ± 39,2 % ; p = 0,40. Les apports énergétiques et protéiques quotidiens étaient significativeme [ABSTRACT FROM AUTHOR]

Published
2014
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229. Lymphoma in Patients with Inflammatory Bowel Disease: A Multicentre Collaborative Study Between GETAID and LYSA.

Author

Muller M, Broséus J, Guilloteau A, Wasse S, Thiéblemont C, Nancey S, Cadiot G, Amiot A, Laharie D, Vieujean S, Bouhnik Y, Martineau C, Michiels C, Hebuterne X, Savoye G, Franchimont D, Seksik P, Beaugerie L, Maynadié M, Feugier P, and Peyrin-Biroulet L

Subjects
Humans, Male, Female, Middle Aged, Case-Control Studies, Retrospective Studies, Adult, Lymphoma epidemiology, Hodgkin Disease epidemiology, Lymphoma, Large B-Cell, Diffuse epidemiology, Lymphoma, Large B-Cell, Diffuse pathology, Crohn Disease complications, Crohn Disease epidemiology, France epidemiology, Lymphoma, Follicular epidemiology, Prognosis, Colitis, Ulcerative complications, Colitis, Ulcerative epidemiology, Inflammatory Bowel Diseases complications, Inflammatory Bowel Diseases epidemiology
Abstract

Background: Inflammatory bowel disease [IBD] is associated with an increased risk of developing lymphoma. Although recent data have clarified the epidemiology of lymphoma in IBD patients, the clinical and pathological characteristics of lymphoma in IBD remain poorly known., Methods: Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d'Étude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] and the Lymphoma Study Association [LYSA]. We characterized clinical and prognostic features for the three most frequent lymphoma subtypes occurring in IBD. We performed a multicentre case-control study. Controls [lymphoma de novo] were matched [5:1] to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, and IPI/FLIPI indexes. Overall survival and progression-free survival were compared between cases and controls., Results: In total, 133 IBD patients with lymphoma were included [males = 62.4%, median age at lymphoma diagnosis = 49 years in males; 42 years in females]. Most had Crohn's disease [73.7%] and were exposed to thiopurines [59.4%]. The most frequent lymphoma subtypes were diffuse large B cell lymphoma [DLBCL, 45.1%], Hodgkin lymphoma [HL, 18.8%], and follicular lymphoma [FL, 10.5%]. When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls [p = 0.0064, hazard ratio = 0.36] or similar [HL and FL]., Conclusions: Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the rarity of this situation, such patients should be managed in expert centres., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2024
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230. Efficacy and Safety of Infliximab Retreatment in Crohn's Disease: A Multicentre, Prospective, Observational Cohort (REGAIN) Study from the GETAID.

Author

Boschetti G, Nachury M, Laharie D, Roblin X, Gilletta C, Aubourg A, Bourreille A, Zallot C, Hebuterne X, Buisson A, Grimaud JC, Bouhnik Y, Allez M, Altwegg R, Viennot S, Vuitton L, Carbonnel F, Paul S, Desseaux K, Lambert J, and Peyrin-Biroulet L

Subjects
Adult, Antibodies, Gastrointestinal Agents therapeutic use, Humans, Infliximab therapeutic use, Prospective Studies, Retreatment, Treatment Outcome, Crohn Disease drug therapy
Abstract

Introduction: The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance., Methods: We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index &gt;150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of &lt;150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic., Results: At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26., Discussion: In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions., (Copyright © 2022 by The American College of Gastroenterology.)

Published
2022
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231. Kidney function monitoring in inflammatory bowel disease: The MONITORED consensus.

Author

Guillo L, Delanaye P, Flamant M, Figueres L, Karam S, Lemoine S, Benezech A, Pelletier AL, Amiot A, Caron B, Stefanescu C, Boschetti G, Bouguen G, Rahier JF, Gornet JM, Hugot JP, Bonnet J, Vuitton L, Nachury M, Vidon M, Uzzan M, Serrero M, Dib N, Seksik P, Hebuterne X, Bertocchio JP, Mariat C, and Peyrin-Biroulet L

Subjects
Consensus, Humans, Inflammatory Bowel Diseases complications, Kidney physiopathology, Gastroenterology standards, Inflammatory Bowel Diseases physiopathology, Kidney Diseases etiology, Kidney Function Tests standards, Practice Guidelines as Topic
Abstract

Background and Aims: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD., Methods: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement., Results: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient., Conclusion: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients., Competing Interests: Conflict of interest L Guillo declares consulting fees for Abbvie. A Amiot declares counseling, boards, lecture, transports or fees from Abbvie, Hospira, Takeda, Gilead, Biocodex, Janssen, Ferring and MSD. B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Takeda. G Boschetti has served as a speaker and advisory board member for Abbvie, Janssen, Ferring, Norgine, Tillotts, Pfizer, Celltrion, Takeda, Amgen, Sandoz. G Bouguen has received lecture fees from Abbvie, Ferring, MSD, Takeda, Otsuka, Amgen, Biogen, Celtrion, Janssen, Tillots and Pfizer and consultant fees from Takeda, Janssen, Mylan, Vifor Pharma and Gilead. JM Gornet has received personal fees from Amgen, Janssen Cilag, Sanofi, Takeda, Roche and Tillots Pharma. J Bonnet has received consulting fees for Amgen. L Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen and Pfizer, and research grants from MSD, Takeda and Pfizer. M Nachury received board membership, consultancy, or lecture fees from Abbvie, Adacyte, Amgen, Arena, CTMA, Celltrion, Ferring, Fresenius-Kabi, Janssen, Mayoli-Spindler, MSD, Pfizer, Takeda. M Uzzan has served as a speaker for Janssen and Abbvie. M Serrero declares lecture and consulting fees for Abbvie, Celltrion, Ferring, Janssen, MSD, Takeda and Tillotts. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. The remaining authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2022
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232. Faster and less invasive tools to identify patients with ileal colonization by adherent-invasive E. coli in Crohn's disease.

Author

Buisson A, Vazeille E, Fumery M, Pariente B, Nancey S, Seksik P, Peyrin-Biroulet L, Allez M, Ballet N, Filippi J, Yzet C, Nachury M, Boschetti G, Billard E, Dubois A, Rodriguez S, Chevarin C, Goutte M, Bommelaer G, Pereira B, Hebuterne X, and Barnich N

Subjects
Biomarkers blood, Biopsy, Colonoscopy, Escherichia coli immunology, Feces microbiology, Female, Humans, Male, Prospective Studies, Saliva microbiology, Antibodies, Bacterial blood, Crohn Disease microbiology, Escherichia coli isolation & purification, Ileum microbiology
Abstract

Background and Aims: The identification of Crohn's disease (CD)-associated adherent and invasive Escherichia coli (AIEC) is time-consuming and requires ileal biopsies. We aimed to identify a faster and less invasive methods to detect ileal colonization by AIEC in CD patients., Methods: CD patients requiring ileo-colonoscopy were consecutively enrolled in this prospective multicenter study. Samples from saliva, serum, stools, and ileal biopsies of CD patients were collected., Results: Among 102 CD patients, the prevalence of AIEC on ileal biopsies was 24.5%. The abundance and global invasive ability of ileal-associated total E. coli were respectively ten-fold (p = 0.0065) and two-fold (p = 0.0007) higher in AIEC-positive (vs. AIEC-negative), while abundance of total E. coli in the feces was not correlated with AIEC status in the ileum. The best threshold of ileal total E. coli was 60 cfu/biopsy to detect AIEC-positive patients, with high negative predictive value (NPV) (94.1%[80.3-99.3]), while the global invasive ability (>9000 internalized bacteria) was able to detect the presence of AIEC with high positive predictive value (80.0% [55.2-100.0]). Overall, 78.1% of the AIEC + patients were colonized by two or less different AIEC strains. The level of serum anti-total E. coli antibodies (AEcAb) was higher in AIEC-positive patients (p = 0.038) with a very high negative predictive value (96.6% [89.9-100.0]) (p = 0.038) for a cut-off value > 1.9 × 10 -3 ., Conclusions: More than two thirds of AIEC-positive CD patients were colonized by two or less AIEC strains. While stools samples are not accurate to screen AIEC status, the AEcAb level appears to be an attractive, rapid and easier biomarker to identify patients with Crohn's disease harboring AIEC., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Published
2021
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233. Endoscopic balloon dilation of colorectal strictures complicating Crohn's disease: a multicenter study.

Author

Tilmant M, Serrero M, Poullenot F, Bouguen G, Pariente B, Altwegg R, Basile P, Filippi J, Vanelslander P, Buisson A, Desjeux A, Laharie D, Le Balch E, Nachury M, Boivineau L, Savoye G, Hebuterne X, Poincloux L, Vuitton L, Brazier F, Yzet C, Lamrani A, Peyrin-Biroulet L, and Fumery M

Subjects
Adult, Constriction, Pathologic, Dilatation methods, Female, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Colonic Diseases complications, Colonic Diseases therapy, Crohn Disease complications, Rectal Diseases complications, Rectal Diseases therapy
Abstract

Introduction: While endoscopic balloon dilation (EBD) is widely used to manage ileal strictures, EBD of colorectal strictures remains poorly investigated in Crohn's disease (CD)., Methods: We performed a retrospective study that included all consecutive CD patients who underwent EBD for native or anastomotic colorectal strictures in 9 tertiary centers between 1999 and 2018. Factors associated with EBD failure were also investigated by logistic regression., Results: Fifty-seven patients (25 women, median age: 36 years (InterQuartile Range, 31-48) were included. Among the 60 strictures, 52 (87%) were native, 39 (65%) measured < 5 cm and the most frequent location was the left colon (27%). Fifty-seven (95%) were non-passable by the scope and 35 (58%) were ulcerated. Among the 161 EBDs performed (median number of dilations per stricture: 2, IQR 1-3), technical and clinical success were achieved for 79% (n = 116/147) and 77% (n = 88/115), respectively. One perforation occurred (0.6% per EDB and 2% per patient). After a median follow-up of 4.3 years (IQR 2.0-8.4), 24 patients (42%) underwent colonic resection and 24 (42%) were asymptomatic without surgery. One colon lymphoma and one colorectal cancer were diagnosed (3.5% of patients) from endoscopic biopsies and at the time of surgery, respectively. No factor was associated with technical or clinical success., Conclusion: EDB of CD-associated colorectal strictures is feasible, efficient and safe, with more than 40% becoming asymptomatic without surgery., (Copyright © 2020. Published by Elsevier Masson SAS.)

Published
2021
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234. Ustekinumab is more effective than azathioprine to prevent endoscopic postoperative recurrence in Crohn's disease.

Author

Buisson A, Nancey S, Manlay L, Rubin DT, Hebuterne X, Pariente B, Fumery M, Laharie D, Roblin X, Bommelaer G, Pereira B, Peyrin-Biroulet L, and Vuitton L

Subjects
Adult, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Azathioprine administration & dosage, Control Groups, Crohn Disease surgery, Female, Gastrointestinal Agents administration & dosage, Gastrointestinal Agents therapeutic use, Humans, Immunosuppressive Agents administration & dosage, Male, Propensity Score, Recurrence, Retrospective Studies, Ustekinumab administration & dosage, Azathioprine therapeutic use, Crohn Disease prevention & control, Immunosuppressive Agents therapeutic use, Secondary Prevention methods, Ustekinumab therapeutic use
Abstract

Background: Preventing postoperative recurrence (POR) is a major concern in Crohn's disease (CD). While azathioprine is an option, no data is available on ustekinumab efficacy in this situation., Aims: We compared the effectiveness of ustekinumab versus azathioprine in preventing endoscopic POR in CD., Methods: We retrospectively collected data from all consecutive CD patients treated with ustekinumab after intestinal resection in 9 centers. The control group (azathioprine alone) was composed of patients who participated in a randomized controlled trial conducted in the same centers comparing azathioprine alone or in combination with curcumin. Propensity score analyses (inversed probability of treatment weighting = IPTW) were applied to compare the two groups. The primary endpoint was endoscopic POR (Rutgeerts' index ≥ i2) at 6 months., Results: Overall, 32 patients were included in the ustekinumab group and 31 in the azathioprine group. The propensity score analysis was adjusted on the main risk factors (smoking, fistulizing phenotype, prior bowel resection, resection length >30 cm and ≥2 biologics before surgery) and thiopurines or ustekinumab exposure prior to surgery making the two arms comparable (∣d∣ < 0.2). After IPTW, the rate of endoscopic POR at 6 months was lower in patients treated with ustekinumab compared to azathioprine (28.0% vs. 54.5%, p = 0.029). After IPTW, the rates of i2b-endoscopic POR (Rutgeerts' index ≥ i2b) and severe endoscopic POR (Rutgeerts' index ≥ i3) were 20.8% versus 42.5% (p = 0.066) and 16.9% versus 27.9% (p = 0.24), in the ustekinumab and azathioprine groups, respectively., Conclusion: Ustekinumab seemed to be more effective than azathioprine in preventing POR in this cohort of CD patients., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Published
2021
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235. Impact of abdominal or pelvic radiotherapy on disease activity in inflammatory bowel disease: a multicentre cohort study from the GETAID.

Author

Broussard D, Rivière P, Bonnet J, Fotsing G, Amiot A, Peyrin-Biroulet L, Rajca S, Buisson A, Gilleta C, Pelletier AL, Serrero M, Bouguen G, Altwegg R, Hebuterne X, Nancey S, Fumery M, Cadiot G, Nahon S, Rahier JF, Gornet JM, Vendrely V, and Laharie D

Subjects
Abdomen, Cohort Studies, Female, Humans, Middle Aged, Retrospective Studies, Crohn Disease, Inflammatory Bowel Diseases
Abstract

Background: Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease., Aim: To assess the impact of radiotherapy on IBD course., Methods: A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6-month periods) before (from S-4 to S-1) and after (from S + 1 to S + 6) radiotherapy and IBD flare during follow-up., Results: Sixty-one patients (32 women, mean age 59 years), with 467 patient semesters of follow-up, treated for digestive (n = 31), urinary tract (n = 23) and gynaecological cancers (n = 7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16-27) from S-4 to S-1; 12% (7-19) from S + 1 to S + 3 (P = 0.15 vs S-4 to S-1) and 16% (10-25) from S + 4 to S + 6 (P = 0.45 vs S-4 to S-1). With a median follow-up of 156 weeks (interquartile range: 82-365), rates of survival without IBD flare at 1 and 3 years after radiotherapy were 82.5% (73.2-93.0) and 70.6% (58.8-84.7). Moderate-to-severe acute radiotherapy-induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare., Conclusion: Most patients with non-active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post-radiotherapy period., (© 2020 John Wiley & Sons Ltd.)

Published
2021
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236. Terminal ileitis and multiple strictures in Crohn's disease: technical notes for a side-to-side strictureplasty over the ileocaecal valve - a video vignette.

Author

Frey S, Maubert A, Hebuterne X, Benizri E, and Rahili A

Subjects
Anastomosis, Surgical adverse effects, Constriction, Pathologic etiology, Constriction, Pathologic surgery, Humans, Recurrence, Treatment Outcome, Crohn Disease complications, Crohn Disease surgery, Ileocecal Valve surgery, Intestinal Obstruction etiology, Intestinal Obstruction surgery
Published
2020
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237. Motivation to pursue anti-TNFα treatment in patients with Crohn's disease - the SPACE motivation study.

Author

D'Amico F, Peyrin-Biroulet L, Vandromme L, Bouhnik Y, Faure P, Nahon S, Hagege H, Hebuterne X, Benkhalifa S, and Nachury M

Subjects
Adult, Crohn Disease physiopathology, Crohn Disease psychology, Female, France, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Patient Satisfaction, Prospective Studies, Surveys and Questionnaires, Treatment Outcome, Adalimumab therapeutic use, Crohn Disease drug therapy, Infliximab therapeutic use, Motivation, Tumor Necrosis Factor Inhibitors therapeutic use
Abstract

Background: Crohn's disease (CD) is a chronic disorder requiring long-term treatment. However, up to 20% of patients interrupt temporarily or permanently anti-TNFα. Primary aim was to identify internal and external factors influencing patient's motivation to pursue anti-TNFα in active CD., Methods: This was a French, multicentre, prospective study enrolling CD patients on anti-TNFα therapy since more than 3 months. Patients completed the Satisfaction of Patients with Crohn's Disease questionnaire (SPACE-Q) and other patient-reported-outcome tools at inclusion visit, and after 6 and 12 months., Results: A total of 274 patients were included: 146 (53.3%) received adalimumab, while 128 (46.7%) infliximab. Most patients (78%) were still treated with anti-TNFα 12 months after enrolment. Patients' perception of necessity (p = 0.01) and concerns (p<0.0001) regarding medication, evaluated through the Belief about Medicines Questionnaire (BMQ), and expectation confirmation towards treatment convenience (p = 0.02), towards efficacy (p = 0.04), and treatment satisfaction (p = 0.03) according to SPACE-Q, correlated with motivation to pursue treatment. Patients with higher treatment satisfaction (p = 0.0004), stronger belief in treatment necessity (p<0.0001) and fewer concerns (p = 0.0002) were more likely to be very motivated., Conclusion: Treatment satisfaction, treatment necessity, and concerns are correlated to motivation to pursue anti-TNFα. Specific questions focused on these patients' perceptions could help physicians to identify patients at risk of non-adherence and prevent therapy interruption., Competing Interests: Declaration of Competing Interest F. D'Amico declares no conflict of interest. L. Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. L. Vandromme has served as consultant for Abbvie Laboratories. Y. Bounhik received consulting and lecture fees from AbbVie, Biogaran, Biogen, Boehringer Ingelheim, Celgene, Ferring, Gilead, Hospira, Janssen, Mayoli Spindler, MSD, Norgine, Pfizer, Roche, Samsung Bioepis, Sandoz, Sanofi, Shire, Takeda, UCB. P.Faure has served as consultant for Abbvie Laboratories. S. Nahon has served as consultant for Abbvie Laboratories. H. Hagège has served as consultant for Abbvie, Alfasigma, Ferring, Janssen, Norgine, Mayoly Spindler, MSD, Takeda, Tillotts. X. Hebuterne has served on advisory boards for Abbvie, Abivax, Alphasigma, ARARD, Arkopharma, Astellas, Baxter, Bristol Myers Squibb, Cellgen, Gilead, Eli Lilly, Enterome, Ferring, Fresenius-Kabi, InDex Pharmaceuticals, Janssen, MSD, Nutricia, Pfizer, Roche, Sanofi-Advantis, SAlix, Sangamo, Takeda, Theravance, Tillots. S. Benkhalifa is employee of Abbvie. M. Nachury has served as consultant for Abbvie, Adacyte, Amgen, Biogen, Ferring, Janssen, Mayoli-Spindler, MSD, and Takeda., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2020
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238. Monitoring of inflammatory bowel disease in 2019: A French consensus for clinical practice.

Author

Bonnaud G, Bouhnik Y, Hagege H, Hebuterne X, Pariente B, Roblin X, and Peyrin-Biroulet L

Subjects
Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Colitis, Ulcerative pathology, Consensus, Consensus Development Conferences as Topic, Crohn Disease pathology, France, Humans, Immunosuppressive Agents therapeutic use, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases pathology, Remission Induction, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Gastroenterologists, Practice Patterns, Physicians'
Abstract

For inflammatory bowel disease, traditional dose escalation approaches that are based on clinical symptoms are being replaced by more aggressive treat-to-target approaches, in which treatment is adjusted promptly when predefined clinical and mucosal targets are not met. There is, however, an ongoing need to combine up-to-date treat-to-target strategies with easy-to-implement recommendations. Herein, we present consensus-recommendations for treatment targets that reflect current best practices in France. Methods Thirty-four gastroenterologists practicing in France participated in a meeting during which consensus statements about treat-to-target strategies for following patients with Crohn's disease (CD) and ulcerative colitis were developed. Targets, their definitions, and the timeframes for reaching them were defined. Consensus was defined as ≥66% of experts agreeing with a statement. Results For both diseases, the agreed targets were: patient related outcomes on disease (PRO-1), patient related outcomes on gastrointestinal symptoms (PRO-2), endoscopic healing and biomarkers of inflammation. Nutritional status has been defined as a target for CD only. Histological healing and transmural healing were not defined as targets. Deadlines to achieve targets and monitoring frequency have been agreed as well. Conclusions These consensus statements provide simple, easy-to-follow guidelines that should help gastroenterologists in France implement treat-to-target approaches, optimize treatments, and thus, reduce the burden of disease., Competing Interests: Declaration of Competing Interest Guillaume BONNAUD: AbbVie, Alfa Sigma, AMGEN, Bouchara-recordati, Ferring, IPSEN, Janssen, Medtronic, MSD, Mylan, Norgine, Pfizer, Takeda, TILLOTS, Vifor Yoram BOUHNIK: AbbVie, Biogaran, Biogen, Boehringer Ingelheim, Celgene, Ferring, Gilead, Hospira, Janssen, Mayoli Spindler, MSD, Norgine, Pfizer, Roche, Samsung Bioepis, Sandoz, Sanofi, Shire, Takeda, UCB. Hervé HAGEGE: Abbvie, Alfasigma, Ferring, Janssen, Mayoly Spindler, MSD, Norgine, Takeda Xavier HEBUTERNE: Abbvie, Abivax, Alphasigma, ARARD, Arkopharma, Astellas, Baxter, Bristol Myers Squibb, Cellgène, Gilead, Eli Lilly, Enterome, Ferring, Janssen, InDex Pharmaceuticals, Pfizer, MSD, Nutricia, Pfizer, Roche, Salix, Sanofi-Advantis, Takeda, Tillots, Theravance Benjamin PARIENTE: AbbVie, Amgen, Biogaran, Ferring, Janssen, MSD, Mylan, Lilly, Pfizer, Takeda. Laurent PEYRIN-BIROULET: AbbVie, Janssen, Ferring, Tillots, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen. Xavier ROBLIN: Abbvie, Amgen, Janssen, MSD, Pfizer, Takeda, Theradiag., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2020
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239. Variation of faecal calprotectin level within the first three months after bowel resection is predictive of endoscopic postoperative recurrence in Crohn's disease.

Author

Boube M, Laharie D, Nancey S, Hebuterne X, Fumery M, Pariente B, Roblin X, Peyrin-Biroulet L, Minet-Quinard R, Pereira B, Bommelaer G, and Buisson A

Subjects
Adult, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Azathioprine therapeutic use, Biomarkers metabolism, Crohn Disease drug therapy, Crohn Disease metabolism, Curcumin therapeutic use, Female, France, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Postoperative Period, Predictive Value of Tests, ROC Curve, Recurrence, Remission Induction, Severity of Illness Index, Time Factors, Treatment Outcome, Young Adult, Colectomy, Crohn Disease surgery, Feces chemistry, Leukocyte L1 Antigen Complex metabolism
Abstract

Background: Early prediction of postoperative recurrence (POR) remains a major concern in Crohn's disease (CD)., Aims: To assess serial faecal calprotectin (Fcal) monitoring within the first three months to predict CD endoscopic POR., Methods: In a multicenter randomized controlled trial, CD patients received azathioprine 2.5 mg/kg/day with oral curcumin (3 g/day) or placebo. Fcal was measured at baseline, one month (M1) and M3. Endoscopic POR at M6 was defined as Rutgeerts' index ≥ i2b (central reading)., Results: Among the 48 patients included, there was no significant difference of median Fcal levels at baseline (p = 0.15), M1 (p = 0.44) and M3 (p = 0.28) between patients with or without endoscopic POR at M6. Fcal kinetics during the first 3 months after surgery was significantly different between the patients with or without POR at M6 (p = 0.021). The median variation between Fcal level at baseline and M3 (ΔFcal M3-M0) was significantly higher in patients with endoscopic POR compared to those without POR (p = 0.01). ΔFcal M3-M0 >+10% demonstrated the best performances to predict endoscopic POR at M6 (AUC=0.73, sensitivity=64.7%[41.1-82.7], specificity=87.5%[68.0-96.3], negative predictive value=77.8%[57.5-91.4] and positive predictive value=78.6%[49.2-95.3])., Conclusion: Fcal variation within the first three months after ileocolonic resection is a promising predictor of early endoscopic POR in CD patients., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2020
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240. Oral Curcumin No More Effective Than Placebo in Preventing Recurrence of Crohn's Disease After Surgery in a Randomized Controlled Trial.

Author

Bommelaer G, Laharie D, Nancey S, Hebuterne X, Roblin X, Nachury M, Peyrin-Biroulet L, Fumery M, Richard D, Pereira B, Goutte M, and Buisson A

Subjects
Azathioprine, Humans, Quality of Life, Recurrence, Treatment Outcome, Crohn Disease drug therapy, Crohn Disease surgery, Curcumin adverse effects
Abstract

Background and Aims: Recurrence of Crohn's disease (CD) after surgery is a major concern. Curcumin has anti-inflammatory properties and induces endoscopic remission in patients with ulcerative colitis. We investigated the efficacy of curcumin vs placebo in preventing post-operative recurrence of CD, based on endoscopic and clinical indices, in patients receiving concomitant thiopurine therapy., Methods: We conducted a double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, of 62 consecutive patients with CD undergoing bowel resection. Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy. We also collected data on CD activity index, results from laboratory tests, and answers to quality of life questionnaires during this 6-month period. The primary endpoint was postoperative recurrence of CD in each group (Rutgeerts' index score ≥i2) at month 6 (determined by central reading). An interim analysis (intent to treat) was scheduled after 50% of the patients were enrolled., Results: At month 6, postoperative recurrence (Rutgeerts' index score ≥i2) occurred in 18 patients (58%) receiving curcumin and 21 patients (68%) receiving placebo (P = .60). A significantly higher proportion of patients receiving curcumin (55%) had a severe recurrence of CD (Rutgeerts' index score ≥i3) than patients receiving placebo (26%) (P = .034). We observed a clinical recurrence of CD (CD activity index score >150) at month 6 in 45% of patients receiving placebo and 30% of patients receiving curcumin (P = .80). Quality of life scores at month 6 did not differ significantly between groups (P = .80). Severe adverse events developed in 6% of patients receiving placebo and 16% of patients receiving curcumin (P = .42)., Conclusions: In a randomized controlled trial of patients who underwent surgery for CD and received thiopurine treatment, we found that curcumin was no more effective than placebo in preventing CD recurrence. There were no significant differences between groups in quality of life or severe adverse events. The study was discontinued after interim analysis due to futility. ClinicalTrials.gov no: NCT 02255370., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2020
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241. Colon capsule endoscopy to screen for colorectal neoplasia in those with family histories of colorectal cancer.

Author

Parodi A, Vanbiervliet G, Hassan C, Hebuterne X, De Ceglie A, Filiberti RA, Spada C, and Conio M

Subjects
Adult, Aged, Colon pathology, Female, Humans, Male, Medical History Taking, Middle Aged, Predictive Value of Tests, Prospective Studies, Sensitivity and Specificity, Capsule Endoscopy methods, Colonoscopy methods, Colorectal Neoplasms diagnosis, Early Detection of Cancer methods
Abstract

Background and Aims: Colon capsule endoscopy (CCE) has been recognized as an alternative for colorectal cancer (CRC) screening in average-risk people. Our aim was to prospectively assess the accuracy of CCE as a screening tool in first-degree relatives (FDRs) of people with CRC by using optical colonoscopy (OC) with segmental unblinding as the reference standard., Methods: Consecutive patients admitted with a CRC diagnosis (index cases) were prospectively evaluated and invited to contact their FDRs. Available FDRs were invited to undergo CCE and OC on the following day, with segmental unblinding of CCE results. Sensitivity, specificity, and predictive values/negative predictive values (PPV/NPV) of CCE were assessed for detecting patients with any polyp ≥6 mm and ≥10 mm., Results: A total of 177 FDRs (median age 57.0 years, 54.8% female) identified from 211 index cases were included. Both CCE and OC were completed in all the included FDRs. Overall, CCE identified 51 of 56 FDRs with polyps ≥6 mm (sensitivity 91%; 95% CI, 81-96) and correctly classified as negative 107 of 121 participants without lesions ≥6 mm (specificity 88%; 95% CI, 81-93). Per-patient positive and negative predictive values for ≥6 mm lesions were 78% (95% CI, 67-87) and 95% (95% CI, 90-98), respectively. CCE detected 24 of 27 patients with polyps ≥10 mm and correctly classified as negative 142 of 150 patients, corresponding to 89% sensitivity and 95% specificity. Post-CCE referral rates to colonoscopy were 37% and 18%, respectively., Conclusions: CCE is an accurate method to screen FDRs of patients with CRC and could be offered as an alternative to those who decline or are unfit for colonoscopy screening. (Clinical trial registration number: NCT01184781.)., (Copyright © 2018. Published by Elsevier Inc.)

Published
2018
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242. NutriCancer: A French observational multicentre cross-sectional study of malnutrition in elderly patients with cancer.

Author

Lacau St Guily J, Bouvard É, Raynard B, Goldwasser F, Maget B, Prevost A, Seguy D, Romano O, Narciso B, Couet C, Balon JM, Vansteene D, Salas S, Grandval P, Gyan E, and Hebuterne X

Subjects
Age Factors, Aged, Aged, 80 and over, Counseling statistics & numerical data, Cross-Sectional Studies, Female, France, Humans, Male, Malnutrition diet therapy, Middle Aged, Nutrition Surveys, Nutritional Support statistics & numerical data, Prevalence, Malnutrition epidemiology, Neoplasms epidemiology, Weight Loss
Abstract

Objectives: To compare the prevalence of malnutrition and nutritional management between elderly (≥70years old) and younger patients (<70years) with cancer., Patients and Methods: This is a post-hoc analysis of NutriCancer 2012 study; a one-day cross-sectional nationwide survey conducted to assess malnutrition in adult patients with cancer in France. Patients diagnosed with cancer at the study date in both inpatient and outpatient settings were included. Data collection was performed by means of questionnaires completed by the physician, the patient and the caregiver., Results: This post-hoc analysis compared 578 elderly patients (27.6%) vs. 1517 younger patients (72.4%). There were significant differences in cancer localization between the groups particularly in gastrointestinal cancer (27% in younger patients vs. 42% in elderly), breast cancer (17% vs 8% in elderly) and oropharyngeal (15% vs. 9% in elderly). Weight loss was significantly more reported in the elderly than in younger patients (73.6% vs. 67.6%, p=0.009). Elderly patients were more frequently malnourished than younger patients (44.9% vs. 36.7%, p=0.0006). Food intake was comparable between the groups; however, physicians overestimated the food intake, particularly in the elderly. The malnutrition management was more frequently proposed in elderly, as dietary advice and oral nutritional supplements, than in younger patients; however, enteral nutrition was significantly less undertaken in the elderly., Conclusion: Malnutrition is prevalent in elderly patients with cancer, and more frequent than in younger patients. There is a need for an early integration of the nutritional counselling in patients with cancer, and particularly in the elderly., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2018
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243. Development of the IBD Disk: A Visual Self-administered Tool for Assessing Disability in Inflammatory Bowel Diseases.

Author

Ghosh S, Louis E, Beaugerie L, Bossuyt P, Bouguen G, Bourreille A, Ferrante M, Franchimont D, Frost K, Hebuterne X, Marshall JK, OʼShea C, Rosenfeld G, Williams C, and Peyrin-Biroulet L

Subjects
Delphi Technique, Female, Humans, Male, Surveys and Questionnaires, Visual Analog Scale, Diagnostic Self Evaluation, Disability Evaluation, Health Status Indicators, Inflammatory Bowel Diseases diagnosis
Abstract

Background: The Inflammatory bowel disease (IBD) Disability Index is a validated tool that evaluates functional status; however, it is used mainly in the clinical trial setting. We describe the use of an iterative Delphi consensus process to develop the IBD Disk-a shortened, self-administered adaption of the validated IBD Disability Index-to give immediate visual representation of patient-reported IBD-related disability., Methods: In the preparatory phase, the IBD CONNECT group (30 health care professionals) ranked IBD Disability Index items in the perceived order of importance. The Steering Committee then selected 10 items from the IBD Disability Index to take forward for inclusion in the IBD Disk. In the consensus phase, the items were refined and agreed by the IBD Disk Working Group (14 gastroenterologists) using an online iterative Delphi consensus process. Members could also suggest new element(s) or recommend changes to included elements. The final items for the IBD Disk were agreed in February 2016., Results: After 4 rounds of voting, the following 10 items were agreed for inclusion in the IBD Disk: abdominal pain, body image, education and work, emotions, energy, interpersonal interactions, joint pain, regulating defecation, sexual functions, and sleep. All elements, except sexual functions, were included in the validated IBD Disability Index., Conclusions: The IBD Disk has the potential to be a valuable tool for use at a clinical visit. It can facilitate assessment of inflammatory bowel disease-related disability relevant to both patients and physicians, discussion on specific disability-related issues, and tracking changes in disease burden over time.

Published
2017
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244. Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial.

Author

Vermeire S, Schreiber S, Petryka R, Kuehbacher T, Hebuterne X, Roblin X, Klopocka M, Goldis A, Wisniewska-Jarosinska M, Baranovsky A, Sike R, Stoyanova K, Tasset C, Van der Aa A, and Harrison P

Subjects
Administration, Oral, Adolescent, Adult, Aged, Analysis of Variance, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Treatment Outcome, Young Adult, Crohn Disease drug therapy, Janus Kinase Inhibitors administration & dosage, Pyridines administration & dosage, Triazoles administration & dosage
Abstract

Background: Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease., Methods: We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. We enrolled eligible patients aged 18-75 years with a documented history of ileal, colonic, or ileocolonic Crohn's disease for 3 months or more before screening, as assessed by colonoscopy and supported by histology, and a Crohn's Disease Activity Index (CDAI) score during screening between 220 and 450 inclusive. Patients were randomly assigned (3:1) to receive filgotinib 200 mg once a day or placebo for 10 weeks. Patients were stratified according to previous anti-tumour necrosis factor alpha exposure, C-reactive protein concentration at screening (≤10 mg/L or >10 mg/L), and oral corticosteroid use at baseline, using an interactive web-based response system. The primary endpoint was clinical remission, defined as CDAI less than 150 at week 10. After week 10, patients were assigned based on responder status to filgotinib 100 mg once a day, filgotinib 200 mg once a day, or placebo for an observational period lasting a further 10 weeks. The filgotinib and placebo treatment groups were compared using ANCOVA models and logistic regression models containing baseline values and randomisation stratification factors as fixed effects. Analyses were done on the intention-to-treat non-responder imputation set. The trial was registered at ClinicalTrials.gov, number NCT02048618., Findings: Between Feb 3, 2014, and July 10, 2015, we enrolled 174 patients with active Crohn's disease confirmed by centrally read endoscopy (130 in the filgotinib 200 mg group and 44 in the placebo group). In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points [95% CI 9-39], p=0·0077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo., Interpretation: Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile., Funding: Galapagos., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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245. Bronchial Aspiration of Capsule Endoscope.

Author

Buscot M, Leroy S, Pradelli J, Chaabane N, Hebuterne X, Marquette CH, and Filippi J

Subjects
Aged, Asphyxia diagnosis, Asphyxia etiology, Humans, Male, Radiography, Thoracic, Respiratory Aspiration complications, Respiratory Aspiration diagnosis, Asphyxia surgery, Bronchi surgery, Bronchoscopy methods, Capsule Endoscopes, Foreign Bodies surgery, Respiratory Aspiration surgery
Abstract

Capsule endoscope aspiration is an increasingly reported complication, potentially responsible for respiratory distress and asphyxia. This adverse event is primarily managed by rigid bronchoscopy when spontaneous expulsion does not occur. This complication is all the more detrimental to patients as it can delay or jeopardize further digestive exploration. We report direct repositioning of the capsule in the stomach at the same time as bronchoscopy, thus making second-line gastrointestinal endoscopy needless., (© 2017 S. Karger AG, Basel.)

Published
2017
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246. Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and zonulin to predict the response to infliximab in ulcerative colitis.

Author

Frin AC, Filippi J, Boschetti G, Flourie B, Drai J, Ferrari P, Hebuterne X, and Nancey S

Subjects
Adolescent, Adult, Aged, Cholera Toxin analysis, Feces chemistry, Female, France, Haptoglobins, Humans, Kaplan-Meier Estimate, Lactoferrin analysis, Leukocyte L1 Antigen Complex analysis, Male, Middle Aged, Neopterin analysis, Prospective Studies, Protein Precursors, Pyruvate Kinase analysis, ROC Curve, Remission Induction, Young Adult, Biomarkers analysis, Colitis, Ulcerative drug therapy, Gastrointestinal Agents therapeutic use, Infliximab therapeutic use
Abstract

Background: Fecal markers might predict the response to anti-TNFα in ulcerative colitis (UC)., Aims: To compare the performance of fecal calprotectin (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon) to predict the response to therapy in active UC patients., Methods: Disease activity from 31 consecutive patients with an active UC, treated with infliximab (IFX) was assessed by the Mayo score at baseline and at week 14 and by the partial Mayo score at W52 and stool samples collected for fecal marker measurements at W0, W2, and W14., Results: At W14, 19 patients (61%) were responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact and fCal levels predicted accurately the response to IFX induction. At W14, fLact, fCal, and fM2-PK were individually reliable markers to predict sustained response at W52. The performances of fNeo and fZon were weaker in this setting., Conclusions: The performance of fM2-PK at W2 to predict response to induction therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact was the best tool to predict adequately the course of the disease at one year under maintenance IFX in UC., (Copyright © 2016. Published by Elsevier Ltd.)

Published
2017
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247. Implementation of the French national consensus for the management of ulcerative colitis into clinical practice.

Author

Bonnaud G, Haennig A, Levy J, Sigur N, Ledit A, Cabarrot P, Faure P, Auzimour C, El Atmani A, Hebuterne X, and Peyrin-Biroulet L

Subjects
Algorithms, Consensus, France epidemiology, Gastroenterology, Humans, Colitis, Ulcerative epidemiology, Colitis, Ulcerative therapy, Decision Support Systems, Clinical, Practice Patterns, Physicians'
Abstract

Background: Recently, treatment algorithms were developed in France additionally to ECCO recommendations that should be used as reference for ulcerative colitis (UC) management. Nevertheless, their implementation in clinical practice remains challenging., Aims: To evaluate the prevalence of the use of these UC management algorithms in 127 patients followed by private gastroenterologists., Methods: Charts of all UC patients seen during the year 2015 (n=127) by 10 gastroenterologists were reviewed. The gastroenterologist's management was then compared to the corresponding algorithm situation and, in case of disagreement, analysed by an expert committee., Results: 94.5% of patients corresponded to a clinical situation described in algorithms. Gastroenterologist's management was adequate to the corresponding algorithm situation in 74.2% of cases. Among the 31 cases of disagreement, the gastroenterologist's decision differed from the algorithm position in 21 cases, and in 76.2% of cases the expert committee would have made the same decision. In the remaining 10 cases, the decision differed from the corresponding algorithm for reasons independent from the gastroenterologist (patient's choice etc.)., Conclusions: French national algorithms for UC management allowed coverage of 95% of clinical cases in real world. In three quarters of cases, these algorithms were strictly followed by private gastroenterologists. Dissemination of these algorithms could optimize and strengthen the practitioner's choice., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2016
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248. Fistula Plug in Fistulising Ano-Perineal Crohn's Disease: a Randomised Controlled Trial.

Author

Senéjoux A, Siproudhis L, Abramowitz L, Munoz-Bongrand N, Desseaux K, Bouguen G, Bourreille A, Dewit O, Stefanescu C, Vernier G, Louis E, Grimaud JC, Godart B, Savoye G, Hebuterne X, Bauer P, Nachury M, Laharie D, Chevret S, and Bouhnik Y

Subjects
Adult, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Rectal Fistula diagnosis, Rectal Fistula etiology, Retrospective Studies, Time Factors, Treatment Outcome, Absorbable Implants, Bioprosthesis, Crohn Disease complications, Digestive System Surgical Procedures methods, Perineum, Prosthesis Implantation methods, Rectal Fistula surgery
Abstract

Background and Aims: Anal fistula plug [AFP] is a bioabsorbable bioprosthesis used in ano-perineal fistula treatment. We aimed to assess efficacy and safety of AFP in fistulising ano-perineal Crohn's disease [FAP-CD]., Methods: In a multicentre, open-label, randomised controlled trial we compared seton removal alone [control group] with AFP insertion [AFP group] in 106 Crohn's disease patients with non- or mildly active disease having at least one ano-perineal fistula tract drained for more than 1 month. Patients with abscess [collection ≥ 3mm on magnetic resonance imaging or recto-vaginal fistulas were excluded. Randomisation was stratified in simple or complex fistulas according to AGA classification. Primary end point was fistula closure at Week 12., Results: In all, 54 patients were randomised to AFP group [control group 52]. Median fistula duration was 23 [10-53] months. Median Crohn's Disease Activity Index at baseline was 81 [45-135]. Fistula closure at Week 12 was achieved in 31.5% patients in the AFP group and in 23.1 % in the control group (relative risk [RR] stratified on AGA classification: 1.31; 95% confidence interval: 0.59-4.02; p = 0.19). No interaction in treatment effect with complexity stratum was found; 33.3% of patients with complex fistula and 30.8% of patients with simple fistula closed the tracts after AFP, as compared with 15.4% and 25.6% in controls, respectively [RR of success = 2.17 in complex fistula vs RR = 1.20 in simple fistula; p = 0.45]. Concerning safety, at Week 12, 17 patients developed at least one adverse event in the AFP group vs 8 in the controls [p = 0.07]., Conclusion: AFP is not more effective than seton removal alone to achieve FAP-CD closure., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2016
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249. Efficacy and safety of adalimumab 80 mg weekly in luminal Crohn's disease.

Author

Bouguen G, Laharie D, Nancey S, Hebuterne X, Flourie B, Filippi J, Roblin X, Trang C, Bourreille A, Babouri A, Bretagne JF, Siproudhis L, and Peyrin-Biroulet L

Subjects
Adult, Crohn Disease pathology, Female, Follow-Up Studies, Humans, Male, Prognosis, Prospective Studies, Remission Induction, Safety, Adalimumab therapeutic use, Anti-Inflammatory Agents therapeutic use, Crohn Disease drug therapy
Abstract

Background: In case of a loss of response to adalimumab, some patients with Crohn's disease may derive benefit from increasing the dosing frequency to 40 mg weekly. Efficacy and safety of adalimumab 80 mg weekly remain unknown., Methods: From February 2011 to September 2012, all adults who had active Crohn's disease, defined at least by Crohn's disease activity index >150 and 1 objective sign of inflammation, and required an adalimumab dose escalation to 80 mg weekly were enrolled in a prospective multicenter cohort study. Crohn's disease activity index and C-reactive protein levels were recorded during the first 14 weeks following adalimumab optimization and at 6 months. All adverse events were recorded., Results: Forty-two patients were included. The median age was 33 years, and the median disease duration was 8.6 years. Adalimumab was associated with steroids in 28% of cases and with immunomodulators in 10% of patients. Within the 14 weeks after adalimumab optimization, 14 patients (33.3%) achieved clinical remission (Crohn's disease activity index <150), and 23 patients (54.8%) had a clinical response. Clinical improvement was associated with a drop in the C-reactive protein level from 18 to 5 mg/L (P = 0.0008). After a median follow-up of 14.5 months, 5 patients underwent major abdominal surgery. Adverse events were reported in 13 patients (31%)., Conclusions: Adalimumab 80 mg weekly seems to be well-tolerated and may be effective in inducing clinical remission in patients with luminal Crohn's disease who failed to respond to 40 mg weekly or 80 mg every other week.

Published
2015
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250. Magnetically guided capsule versus conventional gastroscopy for upper abdominal complaints: a prospective blinded study.

Author

Denzer UW, Rösch T, Hoytat B, Abdel-Hamid M, Hebuterne X, Vanbiervielt G, Filippi J, Ogata H, Hosoe N, Ohtsuka K, Ogata N, Ikeda K, Aihara H, Kudo SE, Tajiri H, Treszl A, Wegscheider K, Greff M, and Rey JF

Subjects
Biopsy, Capsule Endoscopes, Capsule Endoscopy instrumentation, Early Detection of Cancer instrumentation, Equipment Design, Feasibility Studies, Female, Gastroscopy instrumentation, Humans, Magnetics instrumentation, Male, Middle Aged, Patient Preference, Predictive Value of Tests, Prognosis, Prospective Studies, Stomach Neoplasms pathology, Capsule Endoscopy methods, Early Detection of Cancer methods, Gastroscopy methods, Magnetics methods, Stomach Neoplasms diagnosis
Abstract

Objectives: Upper gastrointestinal endoscopy is mostly performed under sedation and has a low yield of relevant gastric lesions in patients without alarm symptoms. Simpler screening tests such as capsule endoscopy could be helpful, but gastric visualization is insufficient with the current passive capsules. A magnetically guided gastric capsule was prospectively evaluated in patients with routine indications for gastroscopy., Methods: A total of 189 symptomatic patients (105 male; mean age 53 y) from 2 French centers subsequently and blindly underwent capsule and conventional gastroscopy by 9 and 6 examiners, respectively. The final gold standard was unblinded conventional gastroscopy with biopsy under propofol sedation. Main outcome was accuracy (sensitivity/specificity) of capsule gastroscopy for diagnosis of major gastric lesions, defined as those lesions requiring conventional gastroscopy for biopsy or removal., Results: Twenty-three major lesions were found in 21 patients. Capsule accuracy was 90.5% [95% confidence interval (CI), 85.4%-94.3%] with a specificity of 94.1% (95% CI, 89.3%-97.1%) and a sensitivity of 61.9% (95% CI, 38%-82%). Accuracy did not correlate with lesion location, gastric luminal visibility, examiner case volume, or examination time. Of the remaining 168 patients, 94% had minor and mostly multiple lesions; the capsule made a correct diagnosis in 88.1% (95% CI, 82.2%-92.6%), with gastric visibility and lesion location in the proximal stomach having significant influence. All patients preferred capsule gastroscopy., Conclusions: In a prospective and strictly blinded study, magnetically guided capsule gastroscopy was shown to be feasible in clinical practice and was clearly preferred by patients. Improvements in capsule technology may render this technique a future alternative to gastroscopy.

Published
2015
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