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1. Extracellular vesicles in COVID-19 convalescence can regulate T cell metabolism and function

Author

Molly S. George, Jenifer Sanchez, Christina Rollings, David Fear, Peter Irving, Linda V. Sinclair, and Anna Schurich

Subjects
Immunology, Virology, Science
Abstract

Summary: Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with disease severity and may be implicated in producing long-covid symptoms. Here, we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 disease. We find that alterations in cellular origin and protein content of EV in COVID-19 convalescence are linked to initial disease severity. We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immune-suppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV—T cell interaction. Our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.

Published
2023
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2. Development and validation of metric-based-training to proficiency simulation curriculum for upper gastrointestinal endoscopy using a novel assessment checklist

Author

Nahla Azzam, Nehal Khamis, Majid Almadi, Faisal Batwa, Fahad Alsohaibani, Abdulrahman Aljebreen, Ahmad Alharbi, Yasser Alaska, Turki Alameel, Peter Irving, and Richard M Satava

Subjects
assessment tool, colonoscopy, curriculum, endoscopy skills, gastroscopy, gastroenterology training, metrics, simulation, training to proficiency, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background/Aims: This study aimed to design a structured simulation training curriculum for upper endoscopy and validate a new assessment checklist. Materials and Methods: A proficiency-based progression stepwise curriculum was developed consisting of didactic, technical and non-technical components using a virtual reality simulator (VRS). It focused on: scope navigation, anatomical landmarks identification, mucosal inspection, retro-flexion, pathology identification, and targeting biopsy. A total of 5 experienced and 10 novice endoscopists were recruited. All participants performed each of the selected modules twice, and mean and median performance were compared between the two groups. Novices pre-set level of proficiency was set as 2 standard deviations below the mean of experts. Performance was assessed using multiple-choice questions for knowledge, while validated simulator parameters incorporated into a novel checklist; Simulation Endoscopic Skill Assessment Score (SESAS) were used for technical skills. Results: The following VRS outcome measures have shown expert vs novice baseline discriminative ability: total procedure time, number of attempts for esophageal intubation and time in red-out. All novice trainees achieved the preset level of proficiency by the end of training. There were no statistically significant differences between experts' and trainees' rate of complications, landmarks identification and patient discomfort. SESAS checklist showed high degree of agreement with the VRS metrices (kappa = 0.83) and the previously validated direct observation of procedural skills tool (kappa = 0.90). Conclusion: The Fundamentals of Gastrointestinal Endoscopy simulation training curriculum and its SESAS global assessment tool have been primarily validated and can serve as a valuable addition to the gastroenterology fellowship programs. Follow up study of trainee performance in workplaces is recommended for consequences validation.

Published
2020
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3. Risk of venous thromboembolism in immune-mediated inflammatory diseases: a UK matched cohort study

Author

Peter Irving, Kaivan Khavandi, James Galloway, Kevin Barrett, Monica Nijher, and Ruth Nicholson

Subjects
Medicine
Abstract

Objectives To describe the risk of venous thromboembolism (VTE), and risk factors for VTE, in people with immune-mediated inflammatory diseases (IMID) (ulcerative colitis, Crohn’s disease (CD), rheumatoid arthritis (RA) and psoriatic arthritis (PsA)), compared with a matched control population.Methods A total of 53 378 people with an IMID were identified over 1999–2019 in the UK Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database and were matched to 213 512 people without an IMID. The association between the presence of any IMID, and each IMID separately, and risk of VTE was estimated using unadjusted and multivariable-adjusted Cox proportional hazards models. The prevalence of VTE risk factors, and associations between VTE risk factors and risk of VTE, were estimated in people with and without an IMID.Results People with an IMID were at increased risk of VTE (adjusted HR [aHR] 1.46, 95% CI 1.36,1.56), compared with matched controls. When assessing individual diseases, risk was increased for CD (aHR 1.74, 95% CI 1.45 to 2.08), ulcerative colitis (aHR 1.27, 95% CI 1.10 to 1.45) and RA (aHR 1.54, 95% CI 1.40 to 1.70) but there was no evidence of an association for PsA (aHR 1.21, 95% CI 0.96 to 1.52). In people with an IMID, independent risk factors for VTE included male sex, overweight/obese body mass index, current smoking, history of fracture, and, across study follow-up, abnormal platelet count.Conclusions VTE risk is increased in people with IMIDs. Routinely available clinical information may be helpful to identify individuals with an IMID at increased future risk of VTE.Observational study registration number Clinicaltrials.gov (NCT03835780).

Published
2020
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4. IBD2020 global forum: results of an international patient survey on quality of care

Author

Peter Irving, Johan Burisch, Richard Driscoll, Mats Olsson, John R Fullarton, Barry S Rodgers-Gray, and Simon PL Travis

Subjects
Inflammatory bowel disease, Crohn disease, Colitis, ulcerative, Surveys and questionnaires, Quality of health care, Medicine, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background/Aims IBD2020 is a global forum for standards of care in inflammatory bowel disease (IBD). The aim of the IBD2020 survey was to identify and describe variations in quality care of IBD. Methods Patients with IBD from Finland, Italy, France, Canada, Germany, UK, Spain and Sweden were surveyed during 2013 to 2014, covering: disease characteristics; impact on life and work; organization and perceived quality of care. Results Seven thousand five hundred and seven patients participated (median age, 39 years [range, 10–103 years]; 2,354 male [31.4%]), including 4,097 (54.6%) with Crohn’s disease (CD) and 3,410 (45.4%) with ulcerative colitis (UC). Median time from symptom onset to diagnosis was 1 year for both CD (range, 0–47 years) and UC (range, 0–46 years), with no clear evidence of improvement in diagnostic delay over the preceding 24 years. Half of the patients (3,429; 50.0%) rated their care as “excellent” or “very good,” with similar results for CD and UC across countries. Five factors were significantly (P

Published
2018
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5. Optimizing Therapies Using Therapeutic Drug Monitoring: Current Strategies and Future Perspectives

Author

Peter Irving, Krisztina Barbara Gecse, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Gastrointestinal Agents, Hepatology, Therapeutic Drug Monitoring, Gastroenterology, Humans, Ulcerative Colitis, Crohn's Disease, Drug Monitoring, Inflammatory Bowel Diseases
Abstract

Therapeutic drug monitoring (TDM) has emerged as a strategy for treatment optimization in inflammatory bowel diseases to maximize benefit and to reach more stringent, objective end points. Optimal drug concentrations in inflammatory bowel disease vary according to treatment target, disease phenotype, inflammatory burden, and timing of sampling during the treatment cycle. This review provides an update on TDM with biologic and oral small molecules, evaluates the role of reactive vs proactive TDM, and identifies the gaps in current evidence. In the future, adaptations to how we use TDM may contribute further to the goal of personalized treatment in patients with IBD.

Published
2022

6. 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

7. Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study

Author

Zhigang Liu, Kaixing Le, Xin Zhou, James L Alexander, Simeng Lin, Claire Bewshea, Neil Chanchlani, Rachel Nice, Timothy J McDonald, Christopher A Lamb, Shaji Sebastian, Klaartje Kok, Charlie W Lees, Ailsa L Hart, Richard C Pollok, Rosemary J Boyton, Daniel M Altmann, Katrina M Pollock, James R Goodhand, Nicholas A Kennedy, Tariq Ahmad, Nick Powell, Madiha Islam, Nick Croft, Bessie Cipriano, Caroline Francia, Nosheen Khalid, Ashley Kingston, Irish Lee, Anouk Lehmann, Kinnari Naik, Kevin Samuels, Nicolene Plaatjies, Hafiza Khatun, Farjana Bokth, Elise Pabriaga, Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Matthew Brown, Benjamin White, Nikolaos Kirkineziadis, Bernadette Tilley, Pennie Porter, Rachel Bryant, Natalia Robaczewska, Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica Mitchell, Sophie Clayton, Louise Rogers, Sugrah Sultan, Melanie Rooney, Charlotte Cottrill, Salil Singh, Chris Dawe, Robert Hull, Natalie Silva, Julie Chadwick, Laura Robertson, Jonathan Manning, Lauren Finlayson, Allison Roebuck, Joy Dawson, Sunil Sonwalkar, Naomi Chambers, Matthew Robinson, Andrew Haigh, Lear Matapure, Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili, Tina Thompson, Mohamed Ahmed, Christos Kontos, Claire Dawson, Christophe Bourges, Isabella Barbutti, Megan E Gozzard, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr, Richard Appleby, Emma Johnson, Eathar Shakweh, Kath Phillis, Rachel Gascoyne, Amanda Crowder, Amanda Whileman, Ian London, Jenny Grounds, Emmeline Martin, Susie Pajak, Jude Price, Kathryn Cawley, Sandra Powell, Nichola Kearsley, Anjan Dhar, Ellen Brown, Amanda Cowton, Kimberley Stamp, Ben Warner, Carmel Stuart, Louise Lacey, Shanika de Silva, Clare Allcock, Philip Harvey, Lesley Jones, Elise Cooke, Jayne Slater, Dominic King, Johanne Brooks, Pearl Baker, Hannah Beadle, Carina Cruz, Debbie Potter, Joe Collum, Farzana Masters, Aashish Kumar, Samantha Coetzee, Mihaela Peiu, Becky Icke, Jill Williams, Meena Raj, Edward Gaynor, Sibongile Chadokufa, Bonita Huggett, Hamza Meghari, Sara El-Khouly, Fevronia Kiparissi, Waffa Girshab, Lynda Russell-Walker, Christopher Jackson, Sara Sidler, Andrew Claridge, Emily Fowler, Laura McCafferty, Lesley Haxton, Peter Irving, Karolina Christodoulides, Angela Clifford, Patrick Dawson, Sailish Honap, Samuel Lim, Raphael Luber, Karina Mahiouz, Susanna Meade, Parizade Raymode, Rebecca Reynolds, Anna Stanton, Sherill Tripoli, Naomi Hare, Sopuluchukwu Odukwe, Senthuran Balachandran, Emma North, Jessica North, Bria Browne, Jessica Cordle, Ella Jameson, Yih Harn Siaw, Lane Manzano, Jonathan Segal, Ibrahim Al-Bakir, Imran Khakoo, Sofiya Portukhay, Nora Thoua, Katherine Davidson, Jagrul Miah, Lisa Canclini, Alex Hall, Hassina Furreed, Christine Mitchell-Inwang, Melony Hayes, Sally Myers, Alison Talbot, Jack Turnbull, Emma Whitehead, Katie Stamp, Alison Pattinson, Verghese Mathew, Leanne Sherris, Julie Wilcox, Sankaranarayanan Ramachandran, Hayley Robertson, Angela Harvey, Lucy Hicks, Tara-Marie Byrne, Leilani Cabreros, Hannah Downing-Wood, Sophie Hunter, Mohammad Aamir Saifuddin, Hemanth Prabhudev, Sharmili Balarajah, Jan Krucznski, Kalliopi Driva, Andrea D'Mello, Parith Shah, Rocio Castro-Seoane, Hajir Ibraheim, Laura E Constable, Jonathan W Lo, Melissa Torkizadeh, Sherine K Hermangild, Helen Sutherland, Elva Wilhelmsen, Katherine Mackintosh, Ajay M Verma, Juliemol Sebastian, Mohammad Farhad Peerally, Anne-marie Guerdette, Susan Coburn, Ching Yee Novem lam, Donna Durrant, Belinda Schaefer, Solange Serna, Muhammad Shahzad, Alexandra Kent, Lee Meng Choong, Benedetta Pantaloni, Pantelis Ravdas, Babu Vadamalayan, Stephen Foley, Becky Arnold, Cheryl Heeley, Wayne Lovegrove, Donna Sowton, Lynne Allsop, Heidi Gregory, Mandy Gill, Megan Holmes, Valeria Balan, Susan Smith, Sarah Turner, Philip J Smith, Alan Steel, Giovanna Bretland, Sarah King, Martina Lofthouse, Lindsey Rigby, Sreedhar Subramanian, David Tyrer, Kate Martin, Christopher Probert, Nikolaos Kamperidis, Temi Adedoyin, Manisha Baden, Jeannette Brown, Feba Chacko, Lisa Young, Michela Cicchetti, Mohammad Saifuddin, Priya Yesupatham, Rohit Gowda, Maureen Williams, Karen Kemp, Rima Akhand, Glaxy Gray, Anu John, Maya John, Tasnim Mohammed, Diamond Sathe, Natasha Jones, Jennifer Soren, Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton, Jacqueline Bartholomew, Elizabeth Denis, Alison Daniels, George MacFaul, Diane Scaletta, Loria Siamia, Felicity Williams, Chloe Green, Zeljka Ver, Chris Lamb, Mary Doona, Ashleigh Hogg, Lesley Jeffrey, Andrew King, R Alexander Speight, Jennifer Doyle, Ruth Owen, Jenny Haworth, Linda Patterson, Vithusa Varnaulasingam, Craig Mowat, Debbie Rice, Susan MacFarlane, Anne MacLeod, Samera Mohammed, Shona Murray, Anne Elliott, Mary Anne Morris, Louise Coke, Grace Hindle, Eirini Kolokouri, Catherine Wright, Claire Lee, Nicola Ward, Adele Dann, Melanie Lockett, Charlotte Cranfield, Louise Jennings, Ankur Srivastava, Lana Ward, Nouf Jeynes, Poonam Ranga, Praveen Rajasekhar, Lisa Gallagher, Jill Ward, Rae Basnett, Judy Murphy, Lauren Parking, Emma Lawson, Stacey Short, David Devadason, Gordon Moran, Neelam Khan, Lauren Tarr, Charmaine Olivia, Samantha Warbarton, Sian Kelly, Jimmy Limdi, Kay Goulden, Asad Javed, Lauren McKenzie, Julie Melville, Eleanor Liu, Joseph Sabine, Patricia Jacob, Denise McSorland, Nick Schofield, Lisa Cornwall, James Quirke, Emma Crook, Anne Turner, Pradeep Bhandari, Michelle Baker-Moffatt, Joanne Dash, Alison Le Poidevin, Hayley Downe, Lucille Bombeo, Helen Blackman, Rebecca Smith, Alan Wiles, Hannah Bloxham, Jose Dias, Evelyn Nadar, Hollie Curgenven, Ellie Gilham, Jonathan Macdonald, Shona Finan, Faye McMeeken, Misbah Mahmood, Stephanie Shields, John Paul Seenan, Des DeSilva, Susanna Malkakorpi, Rachel Carson, Holly Lawrence, Ofori Boateng, Felix Kpodo, Simon Whiteoak, Kelli Edger-Earley, Luke Vamplew, Joanna Samways, Sue Roffe, Sarah Ingram, Joel James, Sharon Botfield, Fiona Hammonds, Clare James, Zoe Berry, Gemma Aspinall, Sarah Hawkins, Marian Parkinson, Helen Gardner-Thorpe, Suzie Marriott, Clare Redstone, Halina Windak, Ana-Marie Adam, Hannah Mabb, Emma Stevenson, Jessica Record, Charles Murray, Cynthia Diaba, Fexy Joseph, Glykeria Pakou, Yvonne Gleeson, Annalyn Nunag, James Berrill, Natalie Stroud, Carla Pothecary, Lisa Roche, Keri Turner, Lisa Deering, Lynda Israel, Evelyn Baker, Maxine Nash, Andrew Fagbemi, Felicia Jennings, Imelda Mayor, Jill Wilson, Alice Wheeler, Nicola Phillips, John Gordon, Emma Levell, Silvia Zagalo, Ina Hoad, Bindu Anil, Richard Russell, Paul Henderson, Margaret Millar, Christopher Alexakis, Natalia Michalak, Cheryl Marriott, Sarah Stone, Veronika Pristopan, John Saunders, Helen Burton, Vanessa Cambridge, Tonia Clark, Charlotte Ekblad, Sarah Hierons, Joyce Katebe, Emma Saunsbury, Rachel Perry, Matthew Brookes, Kathryn Davies, Marie Green, Ann Plumbe, Clare Ormerod, Helen Christensen, Hannah Howlett, Anne Keen, Jonathan Ogor, Marie Greenhaigh, Karen Knowles, Shanzi Yin, Maria Poulaka, Alpha Anthony, Emily Newitt, Fiona Trim, Ruth Casey, Katherine Seymour, Catherine Reed, Lijo Joy, Edward Fogden, Kalisha Russell, Samia Hussain, Anne Phillips, Muaad Abdulla, Jeff Butterworth, Colene Adams, Mandy Carnahan, Elizabeth Buckingham, Danielle Childs, Alison Magness, Jo Stickley, Nichola Motherwell, Louise Tonks, Hannah Gibson, Kate Wistance, Caradog Thomas, Elaine Brinkworth, Lynda Connor, Amanda Cook, Tabitha Rees, Rachel Harford, Sean Farley, Marie Jones, Emma Wesley, Alison Moss, Jacob Lucas, Claire Lorimer, Maria Oleary, Maxine Dixon, Fiona Goodchild, Rebecca Twenlow, Corinne Pawley, Arvind Ramadas, Julie Tregonning, Olaku Okeke, Wendy Jackson, Ioannis Koumoutsos, Viji George, Swapna Kunhunny, Sophie Laverick, Isla Anderson, Sophie Smith, Joan Joyce, Sarala Janarthan, Kamal Patel, Mariam Ali, Hilda Mhandu, Aleem Rana, Katherine Spears, Joana Teixeira, Mark Mencias, Abigail Seaward, Jessica Sousa, Nooria Said, Mark Soomaroo, Valentina Raspa, Asha Tacouri, Nicholas Reps, Rebecca Martin, Tinashe Samakomva, Christian Selinger, Jenelyn Carbonell, Felicia Onovira, Doris Quartey, Alice L'Anson, Andrew Ashworth, Jessica Bailey, Angie Dunn, Gjuzel Bespaloi, Harold Rasalan, Zahid Mahmood, Racheal Campbell, Liane Marsh, Tricia Coughlan, Wisam Jafar, Janet Marrs, Christopher McPheat, Monira Rahman, Sarah Davies, Ruth Habibi, Ellen Jessup-Dunton, Teishel Joefield, Reina Layug, Vinod Patel, Joanne Vere, Victoria Turner, Susan Kilroy, Martina Coulding, Martyn Clark, Jacqueline McCormick, Attiya Nisar, Gareth Walker, Stacey Atkins, Jasmine Growdon, Becky George, Charlotte McNeill, Bryony Reed, Angela Foulds, Catherine Marshall, Michele Allison, Briony Dillon, Rachel Cooney, Lillie Bennett, Louise Bowlas, Sharafaath Shariff, Aileen Fraser, Dwayne Punnette, Rebecca Lambert, Charlotte Bishop-Hurman, Elizabeth Undrell, Katherine Belfield, Said Din, Catherine Addleton, Marie Appleby, Johanna Brown, Kathleen Holding, Catherine Fraser, Janice Birkenshaw, Jodie Williams, Kamille Maulion, Meg Lane, Arita Kravale, Claud Smith, Patricia Hooper, John deCaestecker, Olivia Watchorn, Ellie Clarke, Chris Hayward, Susan Inniss, Lucy Pritchard, Karen Rudge, Amanda Carney, Sarah Griffee, Jervoise Andreyev, Sathish Babu, Caroline Hayhurst, Carol Lockwood, Lynn Osborne, Amanda Roper, Karen Warner, Julia Hindle, Tara Lawrence, Kimberley Netherton, Caroline Watt, Kinga Szymiczek, Shameer Mehta, James Bell, William Blad, Lisa Whitley, Roman Jastrub, Dhamaraj Durai, Mark Baker, Elizabeth John Sivamurugan, Mim Evans, Fraser Cummings, Clare Harris, Amy Jones, Liga Krauze, Sohail Rahmany, Michelle Earl, Jenny Vowles, Audrey Torokwa, Mirela Petrova, Andrew Procter, Jo Stanley, Claudia Silvamoniz, Marion Bettey, Amar Wahid, Zoe Morrison, Rhian Thomas-Turner, Louise Yendle, Jennifer Muller, Marcus Mitchell, John Kirkwood, Anna Barnes, Rakesh Chaudhary, Melanie Claridge, Chiara Ellis, Cheryl Kemp, Ogwa Tobi, Jentus Milton, Emma Johnston, Metod Oblak, Carmen Winpenny, Marie-Louise Svensson, Jo Godden, Marium Ashhar, Debbie Alexander, Kate Covil, Lauranne Derikx, Sryros Siakavellas, Helen Baxter, Scott Robertson, Linda Smith, Beena Poulose, Anne Colemam, Margareta Balint, Gareth Rhys-Jones, Helen Watters, Susan Begg, Beatriz Grosalcalde, Judy Coyle, Kerrie Johns, Rachel Hughes, Janet Phipps, Abigail Taylor, Catherine MacPhee, Suzanne Brooks, Jolene John, Michelle Edwards, Katie Smith, Linda Howard, Dianne Wood, Ajay Muddu, Laura Barman, Janine Mallinson, Tania Neale, Diana Ionita, Kerry Elliot, Alison Turnball, Iola Thomas, Alice Thomas, Kelly Andrews, Jonathon Sutton, Caroline Mulvaney Jones, Julia Roberts, and Jeannie Bishop

Subjects
Hepatology, Gastroenterology, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 291657.pdf (Publisher’s version ) (Open Access) BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p

Published
2023

8. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial

Author

Edouard Louis, Matthieu Resche-Rigon, David Laharie, Jack Satsangi, Nik Ding, Britta Siegmund, Geert D'Haens, Laurence Picon, Peter Bossuyt, Lucine Vuitton, Peter Irving, Stephanie Viennot, Christopher A Lamb, Richard Pollok, Filip Baert, Maria Nachury, Mathurin Fumery, Cyrielle Gilletta, Sven Almer, Shomron Ben-Horin, Yoram Bouhnik, Jean-Frederic Colombel, Erik Hertervig, Jane Andrews, Miles Sparrow, Rupert Leong, Susan Connor, Graham Radforth-Smith, Peter De Cruz, Jan Preiss, Andrea Stallmach, Thomas Liceni, Olaf Grip, Jonas Halfvarson, Dharmaraj Durai, Fraser Cummings, Christian Seilinger, Miles Parkes, James Lindsay, Guy Lambrecht, Philippe Van Hootegem, Jean-François Rahier, Marie Dewitte, Xavier Hebuterne, Elise Chanteloup, Romain Altwegg, Stephane Nancey, Guillaume Bouguen, Guillaume Pineton de Chambrun, Floriant Poullenot, Xavier Roblin, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Bordeaux [Bordeaux], GI Unit, Molecular Medicine Centre, Western General Hospital, Imelda General Hospital, Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Gastroenterology, Guy's and St Thomas' Hospital [London], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Gastroenterology [AZ Delta], AZ Delta, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of Clinical and Experimental Medicine, Linköping University (LIU), European Project: 633168,BIOCYCLE (PHC-13-2014), UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Adult, Hepatology, Crohn Disease, Recurrence, Azathioprine, Gastroenterology, Humans, Tumor Necrosis Factor Inhibitors, Immunosuppressive Agents, Infliximab, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy. Methods: This multicentre, open-label, randomised controlled trial was performed in 64 hospitals in seven countries in Europe and Australia. Adult patients with Crohn's disease in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to either continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group), or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). Randomisation was stratified according to disease duration before start of first anti-TNF treatment (≤2 or >2 years), failure of immunosuppressant therapy before start of infliximab, and presence of ulcers at baseline endoscopy. The patient number and group of each stratum were assigned by a central online randomisation website. Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021. Findings: Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group). 39 patients had a relapse (eight [12%] of 67 in the combination group, 25 [35%] of 71 in the infliximab withdrawal group, six [9%] of 69 in the immunosuppressant withdrawal group). 2-year relapse rates were 14% (95% CI 4–23) in the combination group, 36% (24–47) in the infliximab withdrawal group, and 10% (2–18) in the immunosuppressant withdrawal group (hazard ratio [HR] 3·45 [95% CI 1·56–7·69], p=0·003, for infliximab withdrawal vs combination, and 4·76 [1·92–11·11], p=0·0004, for infliximab withdrawal vs immunosuppressant withdrawal). Of 28 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 25 patients (one of two in the combination group, 22 of 23 in the infliximab withdrawal group, and two of three in the immunosuppressant withdrawal group). The mean time spent in remission over 2 years was 698 days (95% CI 668–727) in the combination group, 684 days (651–717) in the infliximab withdrawal group, and 706 days (682–730) in the immunosuppressant withdrawal group. The difference in restricted mean survival time in remission was –14 days (95% CI –56 to 27) between the infliximab withdrawal group and the combination group and –22 days (–62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group. The 95% CIs contained the non-inferiority threshold (–35 days). We recorded 31 serious adverse events, in 20 patients, with no difference in frequency between groups. The most frequent serious adverse events were infections (four in the combination group, two in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group) and Crohn's disease exacerbation (three in the combination group, four in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group). No death nor malignancy was recorded. Interpretation: In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation. Funding: European Union's Horizon 2020.

Published
2023

16. Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study

Author

Shaji Sebastian, Gareth J Walker, Nicholas A Kennedy, Thomas E Conley, Kamal V Patel, Sreedhar Subramanian, Alexandra J Kent, Jonathan P Segal, Matthew J Brookes, Neeraj Bhala, Haidee A Gonzalez, Lucy C Hicks, Shameer J Mehta, Christopher A Lamb, Shukri Abdale, Abdullah Abbasi, Anwar Abusrewil, Precious Aghimien, Saeed Ahmed, Akram Ali, Amjad Ali, Jad Alkhoury, Patrick Allen, Ammar Al-Rifaie, Richard Appleby, Ramesh Arasaradnam, Naila Arebi, Bradley Arms-Williams, Muteeb Ashraf, Andrea Au, Tamar Avades, Homira Ayubi, Saleha Azhar, Samantha Baillie, Sharmili Balarajah, Aaron Bancil, Abdul Basit, Murad Bayati, Andrew Bell, Alexander Berry, Shivaram Bhat, Joya Bhattacharyya, Sophia Bishop, Laura Blackmore, Ashley Bond, Simon Borg-Bartolo, Emma Botwright, Sonia Bouri, Stephen Boyle, Neil Bradley, Fiona Brailsford, Deborah Britton, Caitlin Brown, Rhys Butcher, Jeffrey Butterworth, Rachel Campbell, Roisin Campbell, Iona Campbell, Ruth Carr, Josiah Carter, Peter Cartlidge, Rajiv Chandy, Kelly Chatten, Rakesh Chaudhary, Desmond Chee, Jonathan Cheesbrough, Antonia Churchhouse, Sara Chughtai, Jennie Clough, Alexander Cole, Johannah Cook, Rachel Cooney, Sarah Cotton, Archibald Coulter, Tamsin Critchlow, Frederic Cuison, Chris Curran, Ana-Maria Darie, Robin Dart, Pantong Davwar, Kasamu Kabiru Dawa, Anjan Dhar, Shahida Din, Kok Leong Diong, Benjamin Disney, Emma Dooks, Louise Downey, Anita D'Souza, Lovesh Dyall, Ali El Rida El Masri, Mary Elias, Holli Evans, Richard Felwick, Michael Finegan, Paul Flanagan, Rishi Fofaria, Steven Chung Ming Fong, Richard Fox, Aileen Fraser, Christian Frunza, Alhassan Ghodeif, Nivedita Ghosh, Leah Gilroy, Larissa Good, John Gordon, Nicola Grasso, Aurelién M Guéroult, James Gulliver, Sarah Guthrie, Markus Gwiggner, Mina Hanna, Christopher Harlow, Wendy Harrison, Ailsa Hart, Barney Hawthorne, Julie Henshaw, Rosaleen Herdman-Grant, Patricia Hooper, Willow Howard, Nasir Hussain, Thomas Hutton, Aye Mya Htun, Peter Irving, Reema Jagdish, Anum Javed, Asima Javed, Nishani Jayasooriya, Matthew Johnson, Emma Johnston, Gareth-Rhys Jones, Cynthia Kanagasundaram, Fotein Karagkouni, Karen Kemp, Cheryl Kemp, Hesham Khalil, Najeebullah Khan, Mais Khasawneh, Bilal Khurshid, Andrew King, Beverley Kirkham, Fiona Kirkham, Flora Kokwaro, Mohamed Korani, Ioannis Koumoutsos, Aditi Kumar, Anish John Kuriakose Kuzhiyanjal, Martyn Lakeland, Sophie Laverick, Charlie Lees, Emma Levell, Scott Levison, Samuel Lim, Yuen-Hui Lim, Jimmy Limdi, James Oliver Lindsay, Jessica Lisle, Alan Lobo, Raphael Luber, Laura Lucaciu, Holly Lyne, Jonathan MacDonald, Aarani Mahalingam, Sara Mahgoub, Ridhima Malakar, Fenella Marley, Joy Mason, Zia Mazhar, Hannah McCaughan, Tracy Naughton, Adam McCulloch, Stuart McIlwaine, Nirmol Meah, Leila Mebarek, Mike Mendall, Radharetnas Meiarasu, Nasir Mir, Tilly Mills, Jentus Milton, Victoria Moffat, Gordon W Moran, Liam Morris, Gary Morrison, Graham Morrison, Robert Mulligan, Charles Murray, Jennifer Murray, Mutwakil Musharaf, Sally Myers, Pineshwari Naeck-Boolauky, Andres Naranjo, Janardhan Navaratnam, Deanna Naylor, Emma Nixon, Kirsty Nixon, Hesam Ahmadi Nooredinvand, Uche Nosegbe, Olaolu Olabintan, Elaine Ong Ming San, Comfort Okpeh, Hayley Owen, Ruth Owen, Christopher Palmer-Jones, Kalyan Peddada, Mohammad Peerally, Rebecca Perkins, Frank Phillips, Keith Pohl, Richard Pollok, Nick Powell, Farah Qayyum, Maria Qurashi, Mohammed Nabil Quraishi, Elizabeth Ratcliffe, Shellie Radford, Sohail Rahmany, Hanin Ramadan, Arvind Ramadas, Anne Reddington, Tom Riley, Peter Rimmer, Susan Ritchie, Jacqueline Roscoe, Konstantina Rosiou, Siobhan Rowland, Joseph Sabine, Aamir Saifuddin, Mark Samaan, Priya Sarkar, Shahzad Sarwar, Ayodele Sasegbon, Jayne Saunders, Gregory Sebepos-Rogers, John Paul Seenan, Christian Selinger, Solange Serna, Sonika Sethi, Matthew Shale, Richard Shenderey, Achuth Shenoy, Yousuf Sherifat, Roosey Sheth, Spyros Siakavellas, Rafid Sikafi, Amar Singh, Salil Singh, Updesh Singh, Ganesh Sivaji, Philip Smith, R Alexander Speight, Andy Spence, Catherine Stansfield, Helen Steed, Kishaani Suseeharan, Maria Tabuso, Donatas Taucius, Joanne Taylor, Amit Thakor, Tony Tham, Gill Townsend, Tristan Townsend, Thomas Troth, Ruth Tunney, Kelly Turner, Nosheen Umar, Vithushan Vakeeswarasarma, Ajay M Verma, Hazel Wallace, Katharina Wallis, Hannah Walton, Bo Wang, Eleanor Warner, Callum Watson, Eleanor Watson, Susie Wen, Monika Widlak, Maureen Williams, Amy Woods, Lisa Younge, and Mansoor Zafar

Subjects
medicine.medical_specialty, Hepatology, business.industry, Incidence (epidemiology), Gastroenterology, Case-control study, medicine.disease, Inflammatory bowel disease, Ulcerative colitis, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Severity of illness, Cohort, Medicine, 030211 gastroenterology & hepatology, business, Historical Cohort, Cohort study
Abstract

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

Published
2021

20. Treat to target versus standard of care for patients with Crohn's disease treated with ustekinumab (STARDUST):an open-label, multicentre, randomised phase 3b trial

Author

Silvio Danese, Severine Vermeire, Geert D'Haens, Julian Panés, Axel Dignass, Fernando Magro, Maciej Nazar, Manuela Le Bars, Marjolein Lahaye, Lioudmila Ni, Ivana Bravata, Frederic Lavie, Marco Daperno, Milan Lukáš, Alessandro Armuzzi, Mark Löwenberg, Daniel R Gaya, Laurent Peyrin-Biroulet, Rodolfo Rocca, Susana Lopes, Flavio Caprioli, Sandro Ardizzone, Ana Echarri Piudo, Paolo Gionchetti, Xavier Roblin, Ursula Seidler, David Andersson, Kamal Patel, Pierre Desreumaux, Simone Saibeni, Gustav From, Miroslav Fedurco, Milos Gregus, Yoram Bouhnik, Andreas Luegering, Rocco Cosintino, Ivan Bunganic, Jaime Ramos, Mariam Aguas Peris, Olivier Dewit, Mariabeatrice Principi, Emma Wesley, Paula Lago, Stephane Nancey, María Dolores Martín Arranz, Pieter Hindryckx, Ambrogio Orlando, Andrea Geccherle, Maria Laura Annunziata, Bu'hussain Hayee, Jozef Balaz, Francisco Portela, Cyrielle Gilletta, Torsten Kucharzik, Miguel Mínguez, Javier Pérez Gisbert, Ana Gutiérrez Casbas, Edouard Louis, Marco Marino, Gareth Parkes, Fraser Cummings, Bindia Jharap, Jens Kjeldsen, Luís Correia, Paula Ministro, Matthias Ebert, Erik Hertervig, Dirk Staessen, Joris Dutré, Arnaud Colard, Graham Morrison, Henning Glerup, Jens Frederik Dahlerup, Frank Wolfhagen, Marian Batovsky, Martin Molnar, Barbora Kadleckova, Paulo Caldeira, David Laharie, Xavier Hebuterne, Bruno Bonaz, Matthieu Allez, Andreas Fischer, Joaquín Ernesto Hinojosa Del Val, Miriam Mañosa Ciria, Jose Manuel Herrera Justiniano, Charlotte Soderman, Rajiv Chandy, Craig Mowat, Peter Irving, Jan Fallingborg, Jan Matous, Tomas Douda, Romain Altwegg, Jose Manuel Benitez, María Teresa Arroyo Villarino, Jordi Guardiola Capón, Daniel Ginard Vicenc, Pieter Dewint, Sven Almer, Sebastien Kindt, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and hepatology, Clinical sciences, and Gastroenterology

Subjects
Adult, STARDUST, BLOOD, Hepatology, Remission Induction, Gastroenterology, Standard of Care, GUIDELINES, C-REACTIVE PROTEIN, Crohn's disease, Crohn Disease, MARKER, randomised phase 3b trial, MANAGEMENT, Humans, Administration, Intravenous, Ustekinumab
Abstract

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

Published
2022

22. 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

23. COVID-19 Vaccine-Induced Antibody and T Cell Responses in Immunosuppressed Patients with Inflammatory Bowel Disease After the Third Vaccine Dose

Author

James L. Alexander, Zhigang Liu, Diana Mūnoz Sandoval, Catherine Reynolds, H. Ibraheim, Sulak Anandabaskaran, Aamir Saifuddin, Rocio Castro Seoane, Nikhil Anand, Rachel Nice, Claire Bewshea, Andrea D'Mello, Laura Constable, Gareth Jones, Sharmili Balarajah, Francesca Fiorentino, Shaji Sebastian, Peter Irving, Lucy Hicks, Horace R.T. Williams, Alexandra Kent, Rachel Linger, Miles Parkes, Klaartje Kok, Kamal Patel, Julian P. Teare, Daniel Altmann, James Goodhand, Ailsa Hart, Charlie Lees, Rosemary J. Boyton, Nicholas A. Kennedy, Tariq Ahmad, Nick Powell, and VIP Study Investigators

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022

25. P037 Effect of Ozanimod Treatment and Discontinuation on Absolute Lymphocyte Count in Moderate-to-Severe Ulcerative Colitis: Results from a Phase 3 Trial

Author

Jean-Frederic, Colombel, primary, Geert, D’Haens, additional, Peter, Irving, additional, AnnKatrin, Petersen, additional, Denesh, Chitkara, additional, Cecilia, Marta, additional, Tianlei, Chen, additional, Lorna, Charles, additional, Silvio, Danese, additional, and Subrata, Ghosh, additional

Published
2021
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26. COVID-19 Vaccine-Induced Antibody Responses are Impaired in IBD Patients Treated with Infliximab or Tofacitinib, but not Thiopurines, Ustekinumab or Vedolizumab

Author

James L. Alexander, Nicholas A. Kennedy, H. Ibraheim, Sulak Anandabaskaran, Aamir Saifuddin, Rocio Castro Seoane, Zhigang Liu, Rachel Nice, Claire Bewshea, Andrea D'Mello, Laura Constable, Gareth Jones, Sharmili Balarajah, Francesca Fiorentino, Shaji Sebastian, Peter Irving, Lucy Hicks, Horace R.T. Williams, Alexandra Kent, Rachel Linger, Rebecca King, Miles Parkes, Klaartje Kok, Kamal Patel, Julian P. Teare, Daniel Altmann, Rosemary J. Boyton, James Goodhand, Ailsa Hart, Charlie Lees, Tariq Ahmad, Nick Powell, and The VIP Study Investigators

Published
2021

27. Ulcerative colitis

Author

Jeremy Sanderson and Peter Irving

Abstract

Ulcerative colitis is a chronic relapsing and remitting disease in which chronic inflammation affects the rectum and extends proximally to a variable extent. The precise aetiology remains unknown but involves an interplay between reduced diversity in the gut microbiota and a genetically dysregulated gut immune system and epithelial barrier. Typical presentation of mild or moderate disease is with a gradual onset of symptoms including diarrhoea, rectal bleeding, and the passage of mucus. Severe disease is characterized by anorexia, nausea, weight loss, and severe diarrhoea, with the patient likely to look unwell with fever, tachycardia, and other signs of volume depletion, and the abdomen may be distended and tympanitic, with reduced bowel sounds and marked colonic tenderness. Diagnosis is usually made on the basis of exclusion of infective colitis by stool culture and the finding of typical diffuse inflammation in the rectum and above at sigmoidoscopy. Management requires rapid control of symptoms with induction therapy followed by maintenance of remission. Mild disease is typically treated with 5-aminosalicyclic acid delivered both orally and by enema, and moderate disease by 5-aminosalicyclic acid and steroids. Patients with severe disease require hospital admission, intravenous steroids, and daily review by both a physician and a surgeon experienced in the management of ulcerative colitis. Ciclosporin or infliximab are used as rescue therapies for steroid-resistant acute severe ulcerative colitis, but colectomy should not be delayed when this is required. Maintenance therapy with immunomodulators and biological therapies are both effective at maintaining remission, and several new biologicals are in clinical trials.

Published
2020

28. Faecal microbiota transplantation for refractory

Author

Aravind Gokul, Tamilarasan, Peter, Irving, Christopher Is, Meadows, and Simon, Goldenberg

Subjects
genetic structures, Clostridium Infections, Humans, Female, Fecal Microbiota Transplantation, Novel Treatment (New Drug/Intervention, Established Drug/Procedure in New Situation), Aged
Abstract

Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.

Published
2019

29. Development and validation of metric-based-training to proficiency simulation curriculum for upper gastrointestinal endoscopy using a novel assessment checklist

Author

Richard M. Satava, Nehal Khamis, Peter Irving, Fahad Alsohaibani, Ahmad Alharbi, Yasser Alaska, Abdulrahman M. Aljebreen, Nahla Azzam, Faisal Batwa, Majid A Almadi, and Turki AlAmeel

Subjects
gastroscopy, medicine.medical_specialty, training to proficiency, education, curriculum, metrics, colonoscopy, medicine, Medical physics, lcsh:RC799-869, endoscopy skills, Set (psychology), Curriculum, business.industry, Gastroenterology, Follow up studies, gastroenterology training, Assessment tool, simulation, Upper gastrointestinal endoscopy, Checklist, Identification (information), lcsh:Diseases of the digestive system. Gastroenterology, Original Article, Metric (unit), business, Kappa
Abstract

Background/Aims: This study aimed to design a structured simulation training curriculum for upper endoscopy and validate a new assessment checklist. Materials and Methods: A proficiency-based progression stepwise curriculum was developed consisting of didactic, technical and non-technical components using a virtual reality simulator (VRS). It focused on: scope navigation, anatomical landmarks identification, mucosal inspection, retro-flexion, pathology identification, and targeting biopsy. A total of 5 experienced and 10 novice endoscopists were recruited. All participants performed each of the selected modules twice, and mean and median performance were compared between the two groups. Novices pre-set level of proficiency was set as 2 standard deviations below the mean of experts. Performance was assessed using multiple-choice questions for knowledge, while validated simulator parameters incorporated into a novel checklist; Simulation Endoscopic Skill Assessment Score (SESAS) were used for technical skills. Results: The following VRS outcome measures have shown expert vs novice baseline discriminative ability: total procedure time, number of attempts for esophageal intubation and time in red-out. All novice trainees achieved the preset level of proficiency by the end of training. There were no statistically significant differences between experts' and trainees' rate of complications, landmarks identification and patient discomfort. SESAS checklist showed high degree of agreement with the VRS metrices (kappa = 0.83) and the previously validated direct observation of procedural skills tool (kappa = 0.90). Conclusion: The Fundamentals of Gastrointestinal Endoscopy simulation training curriculum and its SESAS global assessment tool have been primarily validated and can serve as a valuable addition to the gastroenterology fellowship programs. Follow up study of trainee performance in workplaces is recommended for consequences validation.

Published
2020

30. P092 COMPARISON OF INFLIXIMAB AND ADALIMUMAB CONCENTRATIONS BETWEEN THE ENZYME-LINKED IMMUNOSORBENT ASSAY AND THE HOMOGENEOUS MOBILITY SHIFT ASSAY (HMSA) IN INFLAMMATORY BOWEL DISEASE: AN UPDATE FOLLOWING IMPLEMENTATION OF CORRECTIVE MEASURES FOR THE HMSA

Author

Konstantinos Papamichail, William Clarke, Niels VandeCasteele, Katharine Germansky, Joseph Feuerstein, Gil Melmed, Corey Siegel, Peter Irving, and Adam Cheifetz

Subjects
musculoskeletal diseases, Gastroenterology, Immunology and Allergy
Abstract

Background and aims We previously showed a discrepancy between a commercially available enzyme-linked immunosorbent assay (ELISA) and the homogenous mobility shift assay (HMSA) for both infliximab and adalimumab concentrations in patients with inflammatory bowel disease (IBD).1 Based also on the results of this study, Prometheus Laboratories initiated a comprehensive review of their HMSA assays and found that there was an upward drift for both infliximab and adalimumab over a 2-year period, including when our study was being performed. Prometheus corrected the errant values and reported the revised drug concentrations to physicians. We aimed to compare these two assays following the implementation of these corrective measures. Methods Samples from patients with IBD either on infliximab or adalimumab maintenance therapy were prospectively evaluated using both ELISA (InformTx™, Inform Diagnostics) (for research purposes) and the HMSA (ANSER™, Prometheus Laboratories) (performed clinically). Comparison of drug concentrations between assays was performed as previously described.1 Results In total 74 samples were analysed (infliximab, n=45; adalimumab, n=29). Drug concentrations (median [interquartile range, IQR]) were still significantly higher when measured by the HMSA compared to ELISA for foth infliximab (9 [7.1–12.4] vs. 5.7 [4.8–9] μg/ml; p5 μg/ml (K = 0.299, p=0.005), >7 μg/ml (K = 0.303, p=0.005) or >10 μg/ml (K = 0.323, p=0.003) as therapeutic drug concentrations for infliximab, while for adalimumab was weak using >10 μg/ml as therapeutic drug concentrations (K = 0.437, p=0.004), although overall agreement using either >5 or >7 μg/ml as therapeutic drug concentrations was 97%. Conclusions These data suggest that although the correlation between the ELISA and the HMSA was very good for both infliximab and adalimumab it is difficult to compare absolute drug concentrations. Until commercial assays are properly cross-validated and standardized, assay-dependent drug concentration thresholds may need to be applied to better interpret therapeutic drug monitoring results and it is advisable that patients are monitored with the same assay. 1Inflamm Bowel Dis. 2019 Sep 27. https://doi.org/10.1093/ibd/izz202. [Epub ahead of print]

Published
2020

31. The Clinical and Cost-Effectiveness of 4 Enzyme-Linked Immunosorbent Assay Kits for Monitoring Infliximab in Crohn Disease Patients: Protocol for a Validation Study (Preprint)

Author

Thomas Langford, Zehra Arkir, Anastasia Chalkidou, Kate Goddard, Lamprini Kaftantzi, Mark Samaan, and Peter Irving

Abstract

BACKGROUND Currently, treatment decisions for people with Crohn disease are based on clinical judgment and trial and error. Consequently, people may continue to receive high drug dosages and experience unnecessary toxicity when it is possible to reduce or discontinue without a detrimental effect on clinical outcomes. Therapeutic drug monitoring (TDM) involves regularly testing blood samples for drug and antibody levels that could help clinicians identify the optimal treatment strategy and pre-empt treatment failure. However, heterogeneity in the assays can lead to a discrepancy in results and difficulties in decision-making. Standardization of the kits, and therefore results, would allow clinicians to optimize the use of biologics. Currently, there is also a lack of evidence for the cost-effectiveness of TDM using commercial test kits. OBJECTIVE This study aims to analyze the clinical and cost-effectiveness of 4 commercial enzyme-linked immunosorbent assay (ELISA) kits (LISA TRACKER, IDKmonitor, Promonitor, and RIDASCREEN) to generate evidence which could support a recommendation for wider adoption in the National Health Service. METHODS We propose to carry out a prospective-retrospective predictive biomarker validation study using the blood samples and clinical/utilization data collected during the ongoing SPARE trial (NCT02177071). A total of 200 stored samples from people with Crohn's disease who respond to treatment with infliximab will be used along with clinical and cost data from the trial. We will investigate the relationship between the drug and antidrug antibody levels with the main clinical outcomes (relapse rate at 2 years and time spent in remission), as well as resource utilization and quality of life. RESULTS Funding is being sought to conduct this research. CONCLUSIONS This is the first study to compare the 4 ELISA kits for monitoring infliximab in patients with Crohn disease. It aims to address the uncertainties in the potential benefits of using the technologies for TDM. INTERNATIONAL REGISTERED REPOR PRR1-10.2196/11218

Published
2018

32. Successful faecal microbiota transplant for recurrent

Author

Jonathan, Digby-Bell, Andrew, Williams, Peter, Irving, and Simon, Goldenberg

Subjects
Adult, fluids and secretions, Treatment Outcome, Colonoscopes, Crohn Disease, Ileostomy, digestive, oral, and skin physiology, Clostridium Infections, Humans, Female, Colonoscopy, Fecal Microbiota Transplantation, Novel Treatment (New Drug/Intervention, Established Drug/Procedure in New Situation)
Abstract

We present the first reported case of successful treatment of recurrent Clostridium difficile infection with faecal microbiota transplantation delivered antegrade with a colonoscope through a diverting ileostomy.

Published
2018

33. ECCO IBD curriculum

Author

Jaroslaw Kierkus, Nik Ding, Antonino Spinelli, Peter Bossuyt, Gionata Fiorino, Palle Bager, Peter Lakatos, Vito Annese, David Drobne, Edyta Zagorowicz, Torben Knudsen, Christoph Högenauer, and Peter Irving

Subjects
Transition to Adult Care, medicine.medical_specialty, Consensus, MEDLINE, Comorbidity, Inflammatory bowel disease, Endoscopy, Gastrointestinal, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Intensive care medicine, Curriculum, Irritable bowel syndrome, Patient Care Team, medicine.diagnostic_test, Nutritional Support, business.industry, Gastroenterology, Inflammatory Bowel Diseases, General Medicine, medicine.disease, Endoscopy, 030220 oncology & carcinogenesis, Education, Medical, Continuing, 030211 gastroenterology & hepatology, Clinical Competence, Clinical competence, business
Published
2017

34. αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis

Author

Christopher A, Lamb, John C, Mansfield, Gaik W, Tew, Deena, Gibbons, Anna K, Long, Peter, Irving, Lauri, Diehl, Jeff, Eastham-Anderson, Maria B, Price, Graeme, O'Boyle, David E J, Jones, Sharon, O'Byrne, Adrian, Hayday, Mary E, Keir, Jackson G, Egen, and John A, Kirby

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Integrins, regulatory T cell, Colon, Real-Time Polymerase Chain Reaction, etrolizumab, Th1, Young Adult, CD4+ T cell, inflammatory bowel disease, mucosal immunology, intraepithelial lymphocytes, effector T cell, cytokine, Humans, Th17/1, Aged, ulcerative colitis, Middle Aged, Flow Cytometry, Treg, αEβ7 integrin, Case-Control Studies, helper T cell, CD103, Cytokines, Colitis, Ulcerative, Female, Original Article, Th17
Abstract

Background and Aims: The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7–E-cadherin interactions. Methods: αEβ7+ and αEβ7− colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results: CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7− T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7− lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion: αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology.

Published
2016

35. European evidence based consensus on surgery for ulcerative colitis

Author

Jaroslaw Kierkus, Janindra Warusavitarne, Paulo Kotze, Gianluca Pellino, Ioannis Koutroubakis, PAOLO GIONCHETTI, Simona Maria Bataga, Petr Tsarkov, Marc Marti Gallostra, Antonino Spinelli, Peter Lakatos, Tomas Douda, P. Ronan O'Connell, Christopher Probert, Monica Millan, Fabio Vieira Teixeira, Alastair Windsor, Edyta Zagorowicz, Ingrid Prytz Berset, Gianluca Matteo Sampietro, Paulo Gustavo Kotze, Fernando Magro, Dieter Hahnloser, Torben Knudsen, Eloy Espin-Basany, Javier Die trill, Brankica Mijandrusic sincic, Christoph Högenauer, Peter Irving, Tom Øresland, Willem A. Bemelman, Gianluca M. Sampietro, Antonino Spinelli, Alastair Windsor, Marc Ferrante, Philippe Marteau, Oded Zmora, Paulo Gustavo Kotze, Eloy Espin-Basany, Emmanuel Tiret, Giuseppe Sica, Yves Pani, Arne E. Faerden, Livia Biancone, Imerio Angriman, Zuzana Serclova, Anthony de Buck van Overstraeten, Paolo Gionchetti, Laurents Stassen, Janindra Warusavitarne, Michel Adamina, Axel Digna, Rami Eliakim, Fernando Magro, André D’Hoore on behalf of the European Crohn's and Colitis Organisation (ECCO), [, Fernando Rizzello, ], AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, RS: NUTRIM - R2 - Gut-liver homeostasis, Nutrition and Movement Sciences, MUMC+: MA Maag Darm Lever (9), Interne Geneeskunde, and RS: SHE - R1 - Research (OvO)

Subjects
medicine.medical_specialty, Online discussion, ulcerative colitis mortality, INFLAMMATORY-BOWEL-DISEASE, POPULATION-BASED COHORT, COLORECTAL-CANCER, COLONOSCOPIC SURVEILLANCE, DECISION-ANALYSIS, MORTALITY, RISK, PROGNOSIS, EPIDEMIOLOGY, MALIGNANCY, SURGERY, COLONOSCOPIC SURVEILLANCE, PROGNOSIS, Evidence-based practice, media_common.quotation_subject, education, POPULATION-BASED COHORT, Scopus, MEDLINE, ileal pouch-anal anastomosis, LOW-GRADE DYSPLASIA, COLORECTAL-CANCER, surgery, QUALITY-OF-LIFE, FAMILIAL ADENOMATOUS POLYPOSIS, Voting, medicine, ANTINEUTROPHIL CYTOPLASMIC ANTIBODY, EPIDEMIOLOGY, cancer, POSTOPERATIVE INFECTIOUS COMPLICATIONS, media_common, computer.programming_language, ulcerative colitis, ulcerative colitis mortality, RISK, MALIGNANCY, business.industry, MORTALITY, Gastroenterology, POUCH-ANAL-ANASTOMOSIS, General Medicine, Guideline, digestive system diseases, Surgery, TOTAL ABDOMINAL COLECTOMY, LAPAROSCOPIC SUBTOTAL COLECTOMY, ileal pouch-anal anastomosi, DECISION-ANALYSIS, Working group, business, computer, Delphi, INFLAMMATORY-BOWEL-DISEASE
Abstract

The goal of this consensus initiated by the European Crohn's and Colitis Organisation (ECCO) was to establish European consensus guidelines for the surgical treatment of ulcerative colitis. The strategy to reach the consensus involved several steps and follows the standard operating procedures for consensus guidelines of ECCO. An open call for chairs and participants for this consensus was made (see acknowledgements and www.ecco-ibd). Participants were selected by the Guidelines' Committee of ECCO (GuiCom) on the basis of their publication record and a personal statement. Four working groups (WGs) were formed: WG 1 on the preoperative phase, WG 2 on the intraoperative phase, WG 3 on the postoperative phase and WG 4 on special situations. Participants were asked to answer relevant questions on current practice and areas of controversy related to the surgical treatment of ulcerative colitis based on their experience as well as evidence from the literature (Delphi procedure).1 In parallel, the WG members performed a systematic literature search of their topic with the appropriate key words using Medline/PubMed/ISI/Scopus and the Cochrane database, as well as their own files. Provisional guideline statements (with supporting text) were then written by the WG chairs based upon answers to the questionnaire and were circulated among the WG members, prompting discussions and exchange of literature evidence. The proposed statements and the supporting text were submitted to an online platform for online discussion and two online voting procedures among all Consensus participants for the first voting procedure and also for all national representatives of ECCO for the second voting procedure. The WGs finally met in Belgrade on September 25th 2013 for a final face-to-face discussion and to vote and consent on the statements. Technically this was done by projecting the statements and revising them on screen until a consensus was reached. Consensus was defined …

Published
2015

36. Inflammatory Bowel Disease

Author

Louise Langmead, Peter Irving, Louise Langmead, and Peter Irving

Subjects
Inflammatory bowel diseases--Popular works
Abstract

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, affects 1 person in every 400 in the UK. Between 6,000 and 12,000 new cases of ulcerative colitis are diagnosed every year, and research shows that the number of people with Crohn's disease has been rising steadily. While there are numerous volumes covering the management of IBD aimed at clinicians and several volumes focusing on either ulcerative colitis or Crohn's disease for patients, there are few volumes covering the full spectrum of IBD for patients, families and carers. This patient-centred guide covers all aspects of IBD including common symptoms, tests used to make a diagnosis, treatment and overall management of the condition. Providing up-to-date factual information, it is easy to read and allows quick access to key facts and helpful advice. With consideration given to new developments in the understanding and treatment of inflammation of the bowel, including complementary and alternative therapies, this book will help to improve the overall quality of life for all those affected by this chronic disease.

Published
2008

37. Clinical Dilemmas in Inflammatory Bowel Disease

Author

Peter Irving, MD, MRCP, David Rampton, Fergus Shanahan, Peter Irving, MD, MRCP, David Rampton, and Fergus Shanahan

Subjects
Inflammatory bowel diseases--Decision making, Inflammatory bowel diseases
Abstract

Evidence-based guidance to answer more than 60 controversial clinical questions on inflammatory bowel disease Clinical Dilemmas in Inflammatory Bowel Disease is a practical handbook providing quick but detailed answers to the questions and challenges that you are faced with daily in the clinical setting. Each short chapter addresses a different topic and provides evidence-based guidance on subjects ranging from optimising current management through to special management problems and novel treatments. This book is suitable for all medical professionals involved in the care of patients with IBD: established and trainee gastroenterologists, colorectal surgeons, pathologists, radiologists, specialist nurses, pharmacists, dieticians and counsellors

Published
2006

39. Organized planning in major U.K. companies

Author

Bernard Taylor and Peter Irving

Subjects
Long-range planning, Strategy and Management, Geography, Planning and Development, Economics, Marketing, Finance
Abstract

Corporate Long Range Planning began to be fashionable in Britain in the 1960 's. Now it should be possible for the managers which pioneered this development to analyse their experience for the benefit of others. This article reports the results and conclusions from a detailed study of corporate planning in 27 major British companies, each with 2–8 years experience. The aim was to discover why organized planning was introduced; what factors affected its development and what results were achieved.

Published
1971

40. The Hall Effect and Allied Phenomena in Tellurium

Author

Peter Irving Wold

Subjects
Materials science, chemistry, Condensed matter physics, Hall effect, General Physics and Astronomy, chemistry.chemical_element, Tellurium
Abstract

n/a

Published
1916

41. Adaptation of the British Society of Gastroenterology guidelines on the management of acute severe ulcerative colitis in the context of the COVID-19 pandemic

Author

Shahida Din, Alexandra Kent, Pollok, Richard C., Susanna Meade, Kennedy, Nicholas A., Ian Arnott, Beattie, Mark R., Felix Chua, Rachel Cooney, Robin Dart, James Galloway, Gaya, Daniel R., Subrata Ghosh, Mark Griffiths, Laura Hancock, Richard Hansen, Ailsa Hart, Lamb, Christopher A., Lees, Charlie W., Limdi, Jimmy K., Lindsay, James O., Charlie Murray, Kamal Patel, Nick Powell, Chris Probert, Tim Raine, Christian Selinger, Shaji Sebastian, Smith, Philip J., Tozer, Philip J., Andrew Ustianowski, Lisa Younge, Samaan, Mark A., and Peter Irving

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