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1. Ondansetron for irritable bowel syndrome with diarrhoea: randomised controlled trial

Author: David Gunn, Rabia Topan, Ron Fried, Ivana Holloway, Richard Brindle, Suzanne Hartley, Lorna Barnard, Maura Corsetti, S Mark Scott, Adam Farmer, Ayesha Akbar, Maria Eugenicos, Nigel Trudgill, Kapil Kapur, John McLaughlin, David S Sanders, Arvind Ramadas, Peter Whorwell, Lesley Houghton, Phil G Dinning, Qasim Aziz, Alexander C Ford, Amanda Farrin, and Robin Spiller
Subjects: irritable, serotonin, trial, randomised, ondansetron, transit, placebo-controlled parallel group clinical trial, Medicine
Abstract: Background Irritable bowel syndrome with diarrhoea is characterised by frequent, loose or watery stools with associated urgency, resulting in marked reduction of quality of life. Ondansetron, a 5-hydroxytryptamine-3 receptor antagonist, has been shown to benefit patients with irritable bowel syndrome with diarrhoea. Objective To evaluate the effect of ondansetron in irritable bowel syndrome with diarrhoea. Design Phase III, parallel-group, randomised, double-blind, multicentre, placebo-controlled trial in 400 patients, with embedded mechanistic studies. Setting Hospital, primary care and community. Participants Eighty participants meeting Rome IV criteria for irritable bowel syndrome with diarrhoea. Intervention Ondansetron 4 mg (dose titrated up to two tablets three times a day) or matched placebo for 12 weeks. Main outcome measures Clinical – Primary patient-reported end point was % ‘Food and Drug Administration-defined responders’ over 12 weeks. Secondary end points were worst abdominal pain intensity, worst urgency, stool consistency, stool frequency, anxiety, depression and dyspepsia at 12 and 16 weeks. Main outcome measures Mechanistic – Whole gut transit time, faecal water, protease (FP), bile acids and assessment of rectal sensitivity using a barostat. Results Clinical – The study closed early due to slow recruitment. Between 1 January 2018 and 11 May 2020, 80 patients were recruited and randomised (20% of target), 37 to ondansetron, 43 to placebo. Discontinuations (4 ondansetron; 2 placebo) meant 75 completed the 12-week trial treatment. There were four protocol violations. In the intention-to-treat analysis, 15 (40.5%) on ondansetron were primary end-point responders (95% CI 24.7% to 56.4%), and 12 (27.9%) on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Pain intensity reduction occurred in 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32. Improvement in stool consistency occurred in 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07. Use of rescue medication, loperamide, was lower on ondansetron [7 (18.9%) vs. 17 (39.5%)]. Average stool consistency in the final month of treatment reduced significantly more on ondansetron, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved dyspepsia score (SFLDQ), adjusted mean difference –3.2 points [SE 1.43, 95% CI (–6.1 to –0.4), p = 0.028]. There were no serious adverse events. Mechanistic – mean (SD). Ondansetron increased whole gut transit time between baseline and week 12 by 3.8 (9.1) hours on ondansetron, significantly more than on placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8, p = 0.26. Ondansetron did not significantly alter protease, faecal water or bile acids. Changes in referral pathways substantially reduced referrals, impairing recruitment, which meant the study was underpowered. Conclusion Our results are consistent with previous studies and confirmed ondansetron improves stool consistency and urgency but showed minor effect on pain. We plan to undertake a simplified version of this trial overcoming the changed referral pathways by recruiting in primary care, using software linked to primary care records to identify and randomise patients with irritable bowel syndrome with diarrhoea to ondansetron or placebo and remotely follow their progress; thus minimising barriers to recruitment. Trial registration This trial is registered as ISRCTN17508514. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information. Plain language summary Background Irritable bowel syndrome with diarrhoea is characterised by frequent, loose, or watery bowel movements with marked reduction of quality of life. A previous small study suggested ondansetron benefits patients with irritable bowel syndrome with diarrhoea. Methods A clinical trial aiming to recruit 400 patients meeting established criteria for irritable bowel syndrome with diarrhoea from 18 centres throughout the UK. Patients received either ondansetron or placebo for 12 weeks but neither the investigator and nor patient could tell which they were receiving. They recorded their worst abdominal pain, stool frequency and consistency daily. The main end point was the proportion of patients meeting a standard recommended by the U.S. Food and Drug Administration (FDA). Being called a “FDA responder” meant they showed reductions to both pain and days with loose bowel movements. Other less important end points included pain intensity, stool consistency and frequency. We also measured the time for content to pass through the gut (whole gut transit time). Results The study closed early due to slow recruitment with 80 patients randomised. There were 40.5% of responders in the ondansetron group and 27.9% in the placebo group; however, due to low numbers these differences could be due to chance. Ondansetron produced a significant improvement in average stool consistency in the final month of treatment. Ondansetron slowed whole gut transit time which increased from baseline to 12 weeks by a mean of 3.8 hours, while it fell 2.2 hours on placebo, a difference unlikely to be due to chance. Conclusion These results are consistent with previous studies showing that ondansetron improves stool consistency and slows transit. However, because the numbers recruited were smaller than planned, the apparent improvement in “FDA responder” rate could have been due to chance. A further larger trial is needed to confirm the benefit of ondansetron which should be done in primary care where most patients are to be found. Scientific summary Background Irritable bowel syndrome (IBS), which affects around 10% of the population, accounts for 1.8 million consultations/year in primary care in England and Wales (0.6 million patients). Symptoms of IBS with diarrhoea (IBS-D) include frequent, loose or watery stools with associated urgency, which can severely limit socialising, travelling and eating out, with resulting marked reduction in quality of life and loss of work productivity. Around one-third of all IBS patients meet Rome criteria for IBS-D. When patients are asked to rank symptoms in order of importance, the erratic bowel habit is rated first, followed by abdominal pain and, for those with diarrhoea, urgency. Ondansetron, a 5-hydroxytryptamine-3 (5HT3) receptor antagonist, has an excellent safety record for over 20 years as an antiemetic, but is only exceptionally used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, crossover pilot study, benefited patients with IBS-D. While the current trial was ongoing, a separate trial in the USA using a fixed dose bimodal release formulation (3 mg ondansetron +9 mg delayed release formulation) also reported improvement in stool consistency but not pain. Objectives Our primary aim was to determine the efficacy of generic ondansetron compared to placebo in controlling the symptoms of IBS-D using the US FDA-recommended combined end point in which a responder is defined as a patient who met the response criteria for both pain and bowel habit for 6 out of 12 weeks of the trial. Secondary end points included its effect on the characteristic abnormalities of stool consistency, frequency and urgency as well as abdominal pain, satisfactory relief of IBS symptoms, mood and use of rescue medication and to determine the effect of 12 weeks ondansetron over the 1 month after discontinuation, as well as safety. The study also included mechanistic studies to examine the correlation of rectal sensitivity and compliance, faecal bile acids (FBAs) and proteases and postprandial sigmoid motility with the baseline symptoms of our IBS-D patients. We also attempted to determine whether ondansetron significantly altered these biomarkers compared to placebo. Methods Treatment of irritable bowel syndrome using titrated ondansetron trial (TRITON) was a multisite, parallel-group, randomised, double-blinded, placebo-controlled trial, with embedded mechanistic studies within selected sites. Our aim was to determine the superiority of ondansetron compared with placebo. We aimed to randomise 400 patients with IBS-D on a 1 : 1 basis to receive either ondansetron or placebo. Both treatments were administered for 12 weeks in oral doses ranging from 4 mg every third day to 24 mg daily. Dose titration was undertaken in the first 2 weeks of the study to avoid constipation, which at a standard dose occurs in one-quarter of patients. This was achieved by frequent consultation with the research nurse, starting with 1 × 4 mg tablet per day and increasing in increments every 2 days to a maximum of 2 tablets thrice daily. If constipation developed, the treatment was stopped to allow the return of bowel movements and then restarted at a lower dose, typically one every alternate day or one every second day. Rescue medication of loperamide was discouraged but allowed exceptionally for uncontrolled diarrhoea and was documented in the daily diary. The primary outcome of response for both reduction in pain intensity and improvement in stool consistency was assessed over the 12 weeks post randomisation. Secondary and safety outcomes were measured up to 16 weeks post randomisation. Symptoms that were recorded daily included (1) stool consistency and abdominal pain (measured by both paper diary and daily text message); (2) stool frequency, urgency of defaecation, use of rescue medication (defined as the use of loperamide) over 12 weeks of treatment and the answer to the question in the diary ‘Overall, have you had satisfactory relief from your IBS symptoms in the past week?’. Irritable bowel syndrome symptom severity [measured by the IBS Severity Scoring System (IBS-SSS)], dyspepsia [using the Short Form Leeds Dyspepsia Questionnaire (SFLDQ)], quality of life and mood [using the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression Scale (HADS) questionnaires], and somatic symptoms [using the Patient Health Questionnaire 12 Somatic Symptoms (PHQ-12) questionnaire] were assessed by patient-reported questionnaires at the baseline and 12 weeks post randomisation. The trial also assessed possible underlying mechanisms of any effect of ondansetron on changes in the primary and secondary end points. Whole gut transit was measured at baseline and 12 weeks using radio-opaque markers and an abdominal X-ray. High-resolution manometry was performed at baseline and after 8–11 weeks of treatment at two centres to assess whether ondansetron decreased the number of high-amplitude propagating contractions (HAPCs) or increased the percentage time occupied by cyclical retrograde propagated contractions. Barostat assessment was performed at baseline and after 8–11 weeks of treatment at two centres in order to assess if ondansetron increases rectal compliance or decreases sensitivity (manifested as increased pressure thresholds for pain and urgency). Stool samples were assessed for faecal water % (FW), faecal protease (FP) and FBAs. Clinical results The study closed early due to slow recruitment with just 80 patients randomised; 37 to ondansetron and 43 to placebo. Four patients discontinued ondansetron and one placebo during 12-week randomised treatment. Four were excluded from the per-protocol population due to major protocol violations. In the intention to treat (ITT) analysis, 15 patients (40.5%) on ondansetron achieved the primary end point response [95% confidence interval (CI) 24.7% to 56.4%], compared to 12 (27.9%) patients on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Response for pain intensity reduction was achieved by 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32, adjusted OR 1.61 (0.63 to 4.12). Response for stool consistency improvement was reported by 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07, adjusted OR 2.45 (0.92, 6.52). Overall use of the rescue medication, loperamide, was 39.5% (n = 17) on placebo compared with 18.9% (n = 7) on ondansetron. However, by week 12, loperamide use fell to 13.5% on ondansetron versus 25.6% on placebo. Average stool consistency in the final month of treatment fell significantly more on ondansetron than placebo, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved the dyspepsia score (SFLDQ) significantly more than placebo; the largest reduction being in symptoms of indigestion and nausea. The adjusted mean difference in the total score compared to placebo was –3.2 points [SE 1.43, 95% CI (–6.1, to –0.4), p = 0.028]. Ondansetron was well tolerated with most adverse reactions being mild or moderate and not significantly greater than on placebo. The commonest was constipation, reported in 32% on ondansetron and 23% on placebo, of which 75% and 80%, respectively, were rated as mild. Just two patients withdrew citing constipation as the cause. Mechanistic results Results are expressed as mean (SD). Comparing baseline and week 12 showed ondansetron increased average whole gut transit 3.78 (9.1) hours on ondansetron significantly more than placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8; the difference was not significant, p = 0.26. Too few underwent manometry to allow meaningful assessment of the effect of ondansetron but anecdotally one patient who had a dramatic clinical improvement showed a loss of HAPCs and an increase in retrograde contractions, but this could have been due to chance. Ondansetron appeared not to significantly alter FP, though overall the increase in whole gut transit time from baseline to week 12 was correlated with a decrease in FP. There were no significant changes in FBAs and no evidence that ondansetron altered these though we did confirm that we had effectively excluded those with bile acid diarrhoea (BAD). The ratio of secondary to primary bile acids, a measure of bacterial metabolism of bile acids, increased substantially on ondansetron from 9.7 (7.08) to 21.4 (32.9) and less so on placebo from 22.84 (58.23) to 28.61 (31.42). However, owing to small numbers and wide variability these differences were not significant. Limitations Two previous studies in Nottingham had recruited 120 and 136 IBS-D patients within 2 years so we did not anticipate problems with recruitment. However, changes in referral pathways from primary to secondary care substantially reduced referrals to our coinvestigators who were all in secondary care, thus impairing recruitment. The power calculations required 400 to achieve 90% power to detect a 15% difference in primary end point, so the study is substantially underpowered. Use of loperamide did somewhat complicate interpretation since those on placebo used more rescue medication reducing the size of the effect on transit and stool consistency. Conclusion Despite being underpowered for our primary end point, our results are consistent with previous studies and confirmed ondansetron improves stool consistency but showed little effect on pain. Ondansetron significantly slowed whole gut transit time. Ondansetron reduced sensitivity to rectal distension more than placebo without altering compliance, but numbers were too small to achieve statistical significance. This could plausibly contribute to the reduction in urgency and stool frequency but needs repeating with larger numbers to be sure it was not due to chance. We found no evidence that rectal sensitivity was related to either faecal protease or bile acids. The manometry studies were underpowered but anecdotally ondansetron appeared to alter rectosigmoid motor patterns in a way that could reduce inflow of stool to the rectum. Future work We plan to do a simplified version of this trial, using an efficient and remote process, to overcome the changed referral pathways by recruiting in primary care. We will search for patients who have had a diagnosis of chronic diarrhoea and the recommended screening including a normal full blood count, a negative tissue transglutaminase (excluding coeliac disease) and a normal faecal calprotectin using software linked to primary care records. This will allow rapid screening of large numbers of patients to identify and approach patients with IBS-D who meet criteria to take part in a randomised trial of ondansetron or placebo, thus minimising barriers to recruitment. We would remove the pain threshold, which would increase the number of eligible patients and facilitate recruitment. Not allowing loperamide as rescue medication would simplify interpretation and dropouts would be treated as treatment failures. Further streamlining by removing all additional tests that were included in the current trial, as well as efficient trial processes, including e-consent, remote blood and stool samples (if required), and online questionnaires would also optimise recruitment. Study registration This trial is registered as ISRCTN17508514. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information.
Published: 2023
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2. Enhanced neoplasia detection in chronic ulcerative colitis: the ENDCaP-C diagnostic accuracy study

Author: Ashish Awasthi, Jamie Barbour, Andrew Beggs, Pradeep Bhandari, Daniel Blakeway, Matthew Brookes, James Brown, Matthew Brown, Germaine Caldwell, Samuel Clokie, Ben Colleypriest, Abby Conlin, Shanika de Silva, John de Caestecker, Jonathan Deeks, Anjan Dhar, Mark Dilworth, Edward Fogden, Stephen Foley, Deb Ghosh, Leonie Grellier, Ailsa Hart, Syed Samiul Hoque, Marietta Iacucci, Tariq Iqbal, Jonathan James, Mark Jarvis, Anthoor Jayaprakash, Satish Keshav, Laura Magill, Glenn Matthews, Joel Mawdsley, Simon McLaughlin, Samir Mehta, Kevin Monahan, Dion Morton, Senthil Murugesan, Miles Parkes, Valerie Pestinger, Chris Probert, Arvind Ramadas, Alessandro Rettino, Shaji Sebastian, Naveen Sharma, Michael Griffiths, Joanne Stockton, Venkat Subramanian, Nigel Suggett, Philippe Taniere, Julian Teare, Ajay M Verma, and Yvonne Wallis
Subjects: ulcerative colitis, chronic colitis, cancer, dysplasia, predictive biomarker, dna, methylation, surveillance, colonoscopy, Medicine
Abstract: Background: Chronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection. Objectives: To establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme. Design: Module 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later. Setting: Thirty-one UK hospitals. Participants: Patients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis. Interventions: An optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy. Main outcome: Identifying ulcerative colitis patients with neoplasia. Results: Module 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interval 0.79 to 0.88). Precancerous neoplasia showed a higher area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.84 to 0.92). Background mucosa had poorer discrimination (optimism-adjusted area under the receiver operating characteristic curve was 0.68, 95% confidence interval 0.62 to 0.73). Module 2 was unable to develop a robust next-generation sequencing assay because of the low amplification rates across all genes. In module 3, 818 patients underwent a baseline colonoscopy. The methylation assay (testing non-neoplastic mucosa) was compared with pathology assessments for neoplasia and showed a diagnostic odds ratio of 2.37 (95% confidence interval 1.46 to 3.82; p = 0.0002). The probability of dysplasia increased from 11.1% before testing to 17.7% after testing (95% confidence interval 13.0% to 23.2%), with a positive methylation result suggesting added value in neoplasia detection. To determine added value above colonoscopy alone, a second (reference) colonoscopy was performed in 193 patients without neoplasia. Although the test showed an increased number of patients with neoplasia associated with primary methylation changes, this failed to reach statistical significance (diagnostic odds ratio 3.93; 95% confidence interval 0.82 to 24.75; p = 0.09). Limitations: Since the inception of ENDCaP-C, technology has advanced to allow whole-genome or methylome testing to be performed. Conclusions: Methylation testing for chronic ulcerative colitis patients cannot be recommended based on this study. However, following up this cohort will reveal further neoplastic changes, indicating whether or not this test may be identifying a population at risk of future neoplasia and informing future surveillance programmes. Trial registration: Current Controlled Trials ISRCTN81826545. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 1. See the NIHR Journals Library website for further project information.
Published: 2021
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3. 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

4. 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
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5. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Author: Laurent Peyrin-Biroulet, Jean-François Rahier, Julien Kirchgesner, Vered Abitbol, Sebastian Shaji, Alessandro Armuzzi, Konstantinos Karmiris, Javier P. Gisbert, Peter Bossuyt, Ulf Helwig, Johan Burisch, Henit Yanai, Glen A. Doherty, Fernando Magro, Tamás Molnar, Mark Löwenberg, Jonas Halfvarson, Edyta Zagorowicz, Hélène Rousseau, Cédric Baumann, Filip Baert, Laurent Beaugerie, Jean-Marc Gornet, Jean-Marie Reimund, Xavier Hebuterne, Aurélien Amiot, Franco Armelao, Pierre Blanc, Claudio Papi, Guillaume Pineton De Chambrun, Xavier Roblin, null Chu, Sohail Shariq, Nikolaos Viazis, Jimmy Limdi, Piotr Eder H, Georgios Michalopoulos, Andrew Bell, Livia Biancone, Marie Dewitte, Zia Mazhar, Denis Franchimont, Stephane Nancey, Gilles Macaigne, Maria Beatrice Principi, Mathurin Fumery, Gareth Parkes, Jean-Christophe Valats, Glen Doherty, Guillaume Bouguen, Hersin Tsai, Mohsin Gangi, Natalia Pedersen, Frédéric Heluwaert, Richard Shenderey, Sebastian Zeissig, Jeffrey Butterworth, Fabiana Castiglione, Lynsey Corless, Camille Zallot, Salil Singh, Sunil Sonwalkar, Elizabeth Clayton, Deven Vani, Guy Bellaiche, Martine De Vos, Uri Kopylov, Triana Lobaton, Christophe Locher, Gerassimos Mantzaris, George Abouda, Katie Smith, Michael Sprakes, Angeliki Theodoropoulou, Emma Wesley, Joëlle Bonnet, David Elphick, Cyrielle Gilletta, John Gordon, David Laharie, Antoine Nakad, Ambrogio Orlando, Patrick Dubois, Peter Hasselblatt, Christophe Michiels, Cathryn Preston, Anca Staicu, Lucine Vuitton, Mehdi Kaassis, Ally Speight, Deb Ghosh, Nicolas Mathieu, Anne-Laure Pelletier, Anne Phillips, Romain Altwegg, Irit Avni, null biron, Jonathon Landy, Maria Nachury, Achuth Shenoy, Caroline Trang, Georgios Bamias, Klaudia Farkas, Christian Maaser, Ariella Shitrit, Britta Siegmund, Jérôme Filippi, Colm O'morain, Laurent Costes, David Hobday, Zoltán Szepes, Emma Calabrese, Helen Dallal, Michael Fung, Arvind Ramadas, Bijay Baburajan, Konrad Koss, Christophe Barberis, Anthony Buisson, Morgane Amil, Paola Balestrieri, Matthew Johnson, Maria Tzouvala, Stéphanie Viennot, Ferenc Nagy, Nick Thompson, Laurent Alric, Sunil Samuel, Anne Bourrier, Elise Chanteloup, Emilie Del Tedesco, Marcus Harbord, Alan Lobo, Sally Myers, Richard Pollok, Tariq Ahmad, Rakesh Chaudhary, Christos Karakoidas, Ashraf Soliman, Carmen Stefanescu, Georgios Theocharis, Stijn Vanden Branden, Belén Beltran, Yoram Bouhnik, Arnaud Bourreille, Joana Branco, Ben Colleypriest, Rami Eliakim, Paul Knight, Aoibhlinn O'toole, Virgina Robles, Konstantinos Triantafyllou, Marta Maia Bosca, Guy Lambrecht, Lucia Marquez Mosquera, Simon Panter, Aikaterini Pappa, Marion Simon, Ganesh Sivaji, Christophe Bellanger, Arthur Belle, Natalia Borruel, Laurence Egan, Harald Peeters, Daniel Sharpstone, Ramesh Arasaradnam, José Manuel Benitez, Jens Frederik Dahlerup, Olga Giouleme, Miguel Minguez, Eftychia Tsironi, Angela Variola, Patrick Allen, Lucille Boivineau, Andy Cole, Nina Dib, Fernando Gomollon, Richard Johnston, Konstantinos Katsanos, Nick Kennedy, Marianne Kiszka-Kanowitz, Ignacio Marin-Jimenez, Pál Miheller, Pilar Nos, Othman Saraj, Lars Vinter-Jensen, Eran Zittan, Clotilde Baudry, Xavier Calvet, Marie-Christine Cazelles-Boudier, Jean-Louis Coenegrachts, Garret Cullen, Marco Daperno, Anjan Dhar, Romain Gerard, Nanna Jensen, Nitsan Maharshak, Mark Mcalindon, Simon Mcloughlin, Miles Parkes, Kamal Patel, Armando Peixoto, Dimitrios Polymeros, Francisco Portela, Rodolfo Rocca, Philippe Seksik, Sreedhar Subramanian, Ruth Tennenbaum, Raja Atreya, Oliver Bachmann, Arthur Berger, Renáta Bor, Maire Buckley, Daniel Carpio, María Chaparro, Francesco Costa, Eugeni Domenech, Maria Esteve, Stephen Foley, Jordi Guardiola, Ioannis Koutroubakis, Tanja Kuehbacher, Cécilia Landman, Alessandro Lavagna, Noemí Manceñido, Míriam Mañosa, Maria Dolores Martín-Arranz, Laurianne Plastaras, Maria Lia Scribano, Subhasish Sengupta, Nils Teich, My-Linh Tran-Minh, Evanthia Zampeli, Leila Amininejad, Teresa Arroyo, Alain Attar, Ann-Sofie Backman, Anita Bálint, John Beckly, Shomron Ben Horin, Sónia Bernardo, Ludovic Caillo, Bénédicte Caron, María Shanika de Silva, Anna FábiáN, Gionata Fiorino, Ana Gutierrez, Adi Lahat, Mohamed Masmoudi, Marco Mendolaro, Vinciane Muls, Florian Poullenot, Christopher Probert, Catherine Reenaers, Mariann Rutka, Zaman Sarwari, Joanne Sayer, Beatriz Sicilia, Helena Sousa, Catherine van Kemseke, Yamile Zabana, Marco Astegiano, Paul Banim, Dominik Bettenworth, Médina Boualit, Jacob Broder Brodersen, Angeliki Christidou, Rachel Cooney, João Cortez Pinto, Portugal Marília Cravo, Anneline Cremer, Silvio Danese, Antonio di Sabatino, Jan Fallingborg, Antonio Ferronato, Esther Garcia Planella, Sanjay Gupta, Eran Israeli, Samantha Kestenbaum, Lone Larsen, Elisabeth Macken, Nicoletta Mathou, Ágnes Milassin, Joanna Pofelski, Chiara Ricci, Francisco Rodriguez-Moranta, Martin Schmidt-Lauber, Ian Shaw, Marta Soares, Heithem Soliman, Christos Triantos, Konstantinos Zografos, Anurag Agrawal, Alexandre Aubourg, Manuel Barreiro-de Acosta, Jesús Barrio, Daniel Bergemalm, Fernando Bermejo, Giorgia Bodini, Johan Bohr, Dimitrios Christodoulou, Christophe Claessens, Paul Collins, Ruth de Francisco, Santiago Garcia, Sotirios Georgopoulos, Felix Goutorbe, Chrisostomos Kalantzis, Anastasia Kourikou, Vincent Mace, Georgia Malamut, Paula Ministro, Isabelle Nion Larmurier, Elena Ricart, Mélanie Serrero, Juliette Sheridan, Petra Weimers, Vibeke Andersen, Bruno Arroja, Bernd Bokemeyer, Luis Bujanda, Thibault Degand, Carl Eriksson, Cécile Garceau, Henning Glerup, Idan Goren, Lucina Jackson, Stéphane Koch, Francisco Mesonero, Ingrid Ordas, Pauline Riviere, Simone Saibeni, João Soares, Noémie Tavernier, Klaus Theede, Bella Ungar, Elke Bästlein, Antonio Gasbarrini, Andreas Protopapas, Wolfgang Reindl, Fabrizio Bossa, Ailsa Hart, Franz-Josef Heil, Anthony O'Connor, Bas Oldenburg, Luca Pastorelli, null Stephen patchett, Subramaniam Ramakrishnan, John de Caestecker, Ana Echarri, David Kevans, Jürgen Büning, Rosa Coelho, Jeroen Jansen, Benjamin Koslowski, Christopher Wells, Daniel Ceballos, Ingrid König, Hari Padmanabhan, Timi Patani, Raheel Qureshi, Matthieu Allez, Emmanouil Archavlis, Delphine Bonnet, Luisa Guidi, Deirdre Mcnamara, Piero Vernia, Michael Weidenhiller, Lang Alon, Trine Boysen, Charlotte Delattre, Richard Farrell, Rolf-Achim Krüger, Thierry Paupard, Ida Vind, Flavio Caprioli, Vladimir Gancho, Vincent Quentin, Benjamin Avidan, Geert D’Haens, Jane Mccarthy, Jonathon Snook, Konstantinos Soufleris, Frank Zerbib, Dan Carter, Annekatrien Depla, Thomas Eisenbach, Walter Fries, Nikolaos Grammatikos, Saskia Ilegems, Antonio Lopez-Sanroman, Jacques Moreau, Gabriele Riegler, Svend Rietdijk, Marta Rocha, Isabelle Rosa, Barbara Ryan, Yelena Yeremenko, Arnaud Boruchowicz, Filipe Damião, Foteini Laoudi, Andreas Lügering, Giampiero Macarri, Konstantinos Thomopoulos, Luísa Barros, Thomas Blixt, Aurélien Garros, Sam Khorrami, Harry Sokol, Andreas Sturm, Dan Livovsky, Jochen Maul, Heinrich Miks, Vasileios Papadopoulos, Carsten Schmidt, Yifat Snir, Lise Svenningsen, Wafaa Ahmed, Yelena Broitman, Emmanuel Cuillerier, Prashant Kant, Jan Leyden, Lev Lichtenstein, Susana Lopes, Chloé Martineau, Hugh Mulcahy, Axel Schweitzer, Fiona Van Schaik, Hagar Banai, Pauline Danion, Charlotte Dulery, Herma Fidder, Claire Gay, Hervé Hagege, Florence Harnois, Søren Peter Jørgensen, Jens Müller-Ziehm, Michail Oikonomou, Carolina Palmela, Jörg Schulze/Röske, Mark Smith, Tamar Thurm, Francesca Bresso, Hedia Brixi, John Jones, Padraig Macmathuna, Claire Painchart, Yulia Ron, Marianne Vester-Andersen, Gonçalo Alexandrino, Norbert Börner, Mariana Cardoso, Cristina Chagas, Axel Dignaß, Iris Dotan, Charlotte Hedin, Pantelis Karatzas, Panagiotis Kasapidis, Károly Palatka, Georgios Sakizlis, Ana Wilson, Nick Bosanko, Paulo Caldeira, Charlotte Gagniere, Louise Libier, Camille Meunier, Gero Moog, Audrey Pasquion, Roberta Pica, Ayesha Akbar, Nadia Arab, Guillaume Cadiot, João Carvalho, Claire Charpignon, Laus Fellermann, Sigal Fishman, Gerald Fraser, Nathan Gluck, Mark Hoesl, Jarosław Kierkus, Maria Klopocka, Eduardo Martin Arranz, Luis Menchen, Susanna Nikolaus, Anca Petrache, Cyriel Ponsioen, Sabino Riestra, Pilar Robledo, Cristina Rodriguez, Misheal Samer, Matthias Tischer, Joanna Wypych, Julien Baudon, Cristina Bezzio, Gilles Boschetti, Tom Creed, Maria Giulia Demarzo, Stefano Festa, Andrés Figueroa, Mette Julsgaard, Pablo Navarro, Pablo Perez-Galindo, Cléa Rouillon, Emanuele Sablich, Joan Tosca, Mathias Vidon, Marine Vidon, René-Louis Vitte, Anne Wampach, Isabelle Clerc Urmes, Marc Borie, Mathieu Uzzan, Kelly Chatten, Rimmer Peter, Iqbal Tariq, Marta Cossignani, Fiorella Cañete, Tom Holvoet, Susanne Krasz, Sandra Dias, Hadas Abalia, Aziza Abaza, Gal Abramovich, Ingrid Ackzell, Carol Adams, Catherine Addleton, Erika Alfambra, Alicia Algaba, Clare Allcock, Joanna Allison, Karine Amouriaux, Julie Anderson, Emma Anderson, Saskia Appelmans, Lisa Armstrong, Stacey Atkins, Masoumeh Attaran-Bandarabadi, Yvonne Bailey, Stephanie Bardot, Natasha Beck, Lillie Bennett, Jonathan Phil Bergfeld, Ramdane Berkane, Hanne Boey, Louise Bowlas, Joanne Bradley-Potts, Tracy Brear, Nicole Bretlander-Peters, Ellen Brown, Johanna Brown, Elizabeth Buckingham, Katrien Buellens, Rhian Bull, Maura Burke, Leighanne Burns, Julie Burton, Agness Bwalya, Karine Cabanas, Muriel Callaghan, Océane Camou, Debbie Campbell, Elvira Capoferro, Mandy Carnahan, Cornelia Carnio, Anne Carter, Concetta Casali Clack, Leïla Chedouba, Bessie Cipriano, Sophie Claeys, Manon Closset, Dilek Coban, Sara Cococcia, Carolann Coe, Helen Cole, Emilie Collet, Kayleigh Collins, Isabelle Combes, Emma Connor, Kathryn Constantin, Susan Cooke, Nathanaëlle Cornet, Estelle Corrihons, Pilar Corsino, Rosie Cortaville, Donna Cotterill, Amanda Cowton, Harriet Cox, Viktoria Cripps, Amanda Crowder, Tzufit Cukier, Amelia Daniel, Chris Dawe, Jose de Haan, Rosanna de la Croix, Evva Dejonckheere, Juan Delare Villanegro, Guillaume Delaval, Mariangela Delliponti, Aude Delommez, Emilie Detry, Melanie Dhanaratne, Laura Diez Galan, Marie Dodel, Emma Dooks, Joseph Du Cheyron, Linda Duane, Jennifer Dulling Vulgo Cochran, Simona Dyer, Harvey Dymond, Charlotte Ekblad, Kerry Elliott, Ingrid Emmerson, Irène Eugene-Jolchine, Lorna Fleming, Eve Fletcher, Sarah Ford, Greg Forshaw, Angela Foulds, Caroline Francois, Nicole Fuge, Gal Gafni, Miri Ganon, Olga Garcia Nuñez, Laura Garcia Ramirez, Sophie Gelder, Raimonda Gettkowski, Daniela Gilardi, Paolo Giuffrida, Vincent Gobert, Jo Godden, Nuala Godwin, Kay Goulden, Sharon Graham, Charlotte Green, Marie Green, Aboubakar Gueye, Tuba Guler, Ida Gustavsson, Helena Hadjisavvas, Fiona Hammonds, Christina Hantzi, Marion Hauke, Julie Haydock, Orla Hayes, Lizette Helbo Nislev, Jessica Hochstodter, Ashleigh Hogg, Manuela Hölbing, Maureen Holland, Maartje Holsbergen, Linda Howard, Aviya Hoyda, Robert Hull, Jane Irish, Wendy Jackson, Wendy Janssen, Lesley Jeffrey, Sofia Jourdan, Izabela Jutrowska, Chava Kaniel, Theofilos Karezos, Niamh Kelly, Jessica Kelly, Mary Kennedy, Una Kennedy, Joyce Kibaru, Gemma Kirkman, Janine Klaproth, Corinna Kneese, Andrea Koch, Kathleen Kokke, Martha Koppelow, Sabine Krause, Sabine Krauspe, Petra Kwakkenbos, Nunzia Labarile, Hannah Lang, Marianne Lassailly, Martine Leconte, Linda Lepczynski, Emma Levell, Nina Levhar, Kerstin Lindhort, Jessica Lisle, Beatriz Lopez Cauce, Gabriele Lorenz, Ambra Lovati, Tracey Lowry, Margareta Lund, Anne Lutz Vorderbrügge, Suzanne Maansson, Videsheka Madapathage, Maelys Cheviakoff, Alison Magness, Orla Manley, Catherine Manyoni, Ingke Marg, Antonella Marra, Carole Martins, Arianna Massella, Aurore Mathias, Danielle Mervyn, Charlotte Minsart, Sally Mitchell, Kathleen Monks, Mélanie Montero, Alson Moore, Maren Moser, Alison Moss, Angela Mullen, M. Francisca Murciano, Deanna Naylor, Ansgar Nehus, Anne Nicholson, Sarah Nöding, Sinead Nolan, Janet Nörenberg, Clare Northcott, Jim O'Connell, Alison O’Kelly, Noam Orbach-Zingboim, Judit Orobitg, Charlene Otieno, Charlotte Owen, Sarah Patch, Maor Pauker, Renate Pauli, Harriet Pearson, Falgon Peggy, Séverine Petit, Christine Petrissans, Simona Piergallini, Lucy Pippard, Laura Pitt, Gabriella Pócsik, Yoann Poher, Chloé Pomes, Lucy Pritchard, Laura Puchades, Sheena Quaid, Aleem Rana, Dana Raynard, Mykla Reilly, Sonja Reinert, Manuela Reinknecht, Baerbel Renner, Rob Reynolds, Giulia Rizzuto, Matthew Robinson, Joke Robrechts, Eva M. Rodriguez, Efrat Rosenblum, Tamlyn Russel, Ibiyemi Sadare, Noa Salama, Toos Schakel, Anja Schauer, Elisa Schiavoni, Caroline Shaw, Sarah Shelton, Virginie Sicart, Elodie Siouville, Orla Smith, Théo Soude, Sophie Stephenson, Elaine Stephenson, Marjan Steppe, An Sterkx, Jo Stickley, Kathleen Sugrue, Natalia Swietec, Charlotte Tasiaux, Bhavneet Thamu, Susane Thomas, Ogwa Tobi, Kahina Touabi, Shifra Tovi, Julie Tregonning, Laura Turchini, Julia Unkhoff, Olesya Unruh, Nurcan Uzun, Frauke Van Aert, Sandrine Vanden Bergh, Louise Vandenbroucke, Laura Vansteenkiste, Shay Vardit, Valentin Vergriete, Elaine Walker, Eleanor Warner, Olivia Watchorn, Ekaterina Watson, Marie-Claire Wauthier, Belgium Maria Weetman, Margaret Weston, Wiebke West-Petroschka, Susann Wienecke, Kerstin Wierling, Miriam Wiestler, Rebecca Wilcox, Elva Wilhelmsen, Angharad Williams, Georgina Williamson, Deborah Wilson, Kate Wistance, Nicolas Wortmann, Subie Wurie, Karin Yadgar, Gail Young, Megan Young, Julien Aucouturier, Marie- Jo Bertin, Hasnae Bougrine, Marie Coisnon, Antoine Defrance, Kati Gutierrez, Amel Harouz, Laure Jerber, Aida Khlifi, Amina Kirati, Nasaladjine Liworo, Maude Logoltat, Charlotte Mailhat, Chancely M'Bayi, Yasmina Medane, Dalal Merkhoufa, Saouda Mohamed Elhad, Bertille Monthe, Fanny Moyon, Pascaline Rabiega, Jennifer Sekela, Charlotte Thilloy, Naima Hamamouche, Frederic Partisotti, Patrick Blandin, Hocine Mokhtari, Laure Coutard, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Gastroenterology and hepatology, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Biological Products, Hepatology, Efficacy, Lymphoma, Tumor Necrosis Factor-alpha, Inflammatory Bowel Disease, Gastroenterology, Biologics, Crohn Disease/diagnosis, Inflammatory Bowel Diseases/chemically induced, Colitis, Ulcerative/diagnosis, Cohort Studies, Necrosis, Immunologic Factors/adverse effects, Humans, Female, 03.02. Klinikai orvostan, Prospective Studies, Safety, I-CARE, Cancer, Immunosuppressive Agents
Abstract: BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).
Published: 2022
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6. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study

Author: Nicholas A Kennedy, Graham A Heap, Harry D Green, Benjamin Hamilton, Claire Bewshea, Gareth J Walker, Amanda Thomas, Rachel Nice, Mandy H Perry, Sonia Bouri, Neil Chanchlani, Neel M Heerasing, Peter Hendy, Simeng Lin, Daniel R Gaya, J R Fraser Cummings, Christian P Selinger, Charlie W Lees, Ailsa L Hart, Miles Parkes, Shaji Sebastian, John C Mansfield, Peter M Irving, James Lindsay, Richard K Russell, Timothy J McDonald, Dermot McGovern, James R Goodhand, Tariq Ahmad, Vinod Patel, Zia Mazhar, Rebecca Saich, Ben Colleypriest, Tony C Tham, Tariq H Iqbal, Vishal Kaushik, Senthil Murugesan, Salil Singh, Sean Weaver, Cathryn Preston, Assad Butt, Melissa Smith, Dharamveer Basude, Amanda Beale, Sarah Langlands, Natalie Direkze, Franco Torrente, Juan De La Revella Negro, Chris Ewen MacDonald, Stephen M Evans, Anton V J Gunasekera, Alka Thakur, David Elphick, Achuth Shenoy, Chuka U Nwokolo, Anjan Dhar, Andrew T Cole, Anurag Agrawal, Stephen Bridger, Julie Doherty, Sheldon C Cooper, Shanika de Silva, Craig Mowat, Phillip Mayhead, Charlie Lees, Gareth Jones, James W Hart, Lisa Gervais, Paul Dunckley, Tariq Mahmood, Paul J R Banim, Sunil Sonwalkar, Deb Ghosh, Rosemary H Phillips, Amer Azaz, Richard Shenderey, Lawrence Armstrong, Claire Bell, Radhakrishnan Hariraj, Helen Matthews, Hasnain Jafferbhoy, Veena Zamvar, John S De Caestecker, Anne Willmott, Richard Miller, Palani Sathish Babu, Christos Tzivinikos, Stuart L Bloom, Guy Chung-Faye, Nicholas M Croft, John ME Fell, Marcus Harbord, Ailsa Hart, Ben Hope, James O Lindsay, Joel E Mawdsley, Alistair McNair, Kevin J Monahan, Charles D Murray, Timothy Orchard, Thankam Paul, Richard Pollok, Neil Shah, Matt W Johnson, Anita Modi, Kasamu Dawa Kabiru, B K Baburajan, Bim Bhaduri, Andrew Adebayo Fagbemi, Scott Levison, Jimmy K Limdi, Gill Watts, Stephen Foley, Arvind Ramadas, George MacFaul, John Mansfield, Leonie Grellier, Mary-Anne Morris, Mark Tremelling, Chris Hawkey, Sian Kirkham, Charles PJ Charlton, Astor Rodrigues, Alison Simmons, Stephen J Lewis, Jonathon Snook, Mark Tighe, Patrick M Goggin, Aminda N De Silva, Simon Lal, Mark S Smith, Simon Panter, Suranga Dharmisari, Martyn Carter, David Watts, Zahid Mahmood, Bruce McLain, Sandip Sen, Anna J Pigott, David Hobday, Emma Wesley, Richard Johnston, Cathryn Edwards, John Beckly, Deven Vani, Subramaniam Ramakrishnan, Rakesh Chaudhary, Nigel J Trudgill, Rachel Cooney, Andy Bell, Neeraj Prasad, John N Gordon, Matthew J Brookes, Andy Li, Stephen Gore, and Simmons, A
Subjects: Adult, Male, medicine.medical_specialty, Antibodies, Cohort Studies, Leukocyte Count, Young Adult, 03 medical and health sciences, Drug withdrawal, 0302 clinical medicine, Crohn Disease, Risk Factors, Internal medicine, Azathioprine, medicine, Adalimumab, Humans, Prospective Studies, Treatment Failure, Adverse effect, Prospective cohort study, Serum Albumin, Proportional Hazards Models, Crohn's disease, Hepatology, Mercaptopurine, business.industry, Smoking, Age Factors, Gastroenterology, Middle Aged, medicine.disease, Infliximab, Clinical trial, Methotrexate, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, Tumor Necrosis Factor Inhibitors, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, Cohort study, medicine.drug
Abstract: BACKGROUND: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal. METHODS: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure. FINDINGS:We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p
Published: 2019
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7. Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial

Author: Arvind Ramadas, Roisin Bevan, Matthew D. Rutter, Colin J Rees, J Painter, Laura J Neilson, Paul Bassett, Zacharias P. Tsiamoulos, Zoe Hoare, Brian P. Saunders, Gayle Clifford, Wee Sing Ngu, Thomas J. Lee, John G Silcock, and Nicola Totton
Subjects: Adenoma, Male, 0301 basic medicine, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Colonoscopy, colorectal adenomas, colorectal cancer, colorectal cancer screening, law.invention, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Mass Screening, Intubation, colonic adenomas, Adverse effect, Mass screening, Colonoscopes, medicine.diagnostic_test, business.industry, Gastroenterology, Endoscopy, Equipment Design, Middle Aged, medicine.disease, Quality Improvement, 030104 developmental biology, England, Female, 030211 gastroenterology & hepatology, Differential diagnosis, Colorectal Neoplasms, business
Abstract: ObjectiveLow adenoma detection rates (ADR) are linked to increased postcolonoscopy colorectal cancer rates and reduced cancer survival. Devices to enhance mucosal visualisation such as Endocuff Vision (EV) may improve ADR. This multicentre randomised controlled trial compared ADR between EV-assisted colonoscopy (EAC) and standard colonoscopy (SC).DesignPatients referred because of symptoms, surveillance or following a positive faecal occult blood test (FOBt) as part of the Bowel Cancer Screening Programme were recruited from seven hospitals. ADR, mean adenomas per procedure, size and location of adenomas, sessile serrated polyps, EV removal rate, caecal intubation rate, procedural time, patient experience, effect of EV on workload and adverse events were measured.Results1772 patients (57% male, mean age 62 years) were recruited over 16 months with 45% recruited through screening. EAC increased ADR globally from 36.2% to 40.9% (P=0.02). The increase was driven by a 10.8% increase in FOBt-positive screening patients (50.9% SC vs 61.7% EAC, PConclusionEV significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection.Trial registration numberNCT02552017, Results; ISRCTN11821044, Results.
Published: 2018
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8. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease

Author: Timothy R. Orchard, Rosemary H Phillips, Stephen M. Evans, Arvind Ramadas, Paul R. Banim, Guy Chung-Faye, Subramaniam Ramakrishnan, Simon Panter, Leonie Grellier, Hasnain Jafferbhoy, Nigel Trudgill, Thankam Paul, Sian Kirkham, Anna J Pigott, M J Carter, Juan De La Revella Negro, Lisa Gervais, Zia Mazhar, Suranga Dharmisari, Richard A. Miller, Cathryn Preston, Alison Simmons, Rachel Cooney, Natalie C. Direkze, Deb Ghosh, Christian P. Selinger, Andrew A. Fagbemi, Rakesh Chaudhary, J R Fraser Cummings, Stephen Gore, James O. Lindsay, Tony C.K. Tham, David Hobday, Charles Murray, David Watts, Anne Willmott, Gill Watts, Sandip Sen, Mark Reppell, Amer Azaz, Shaji Sebastian, Neil Chanchlani, R B Johnston, Ben Hope, Salil Singh, Stephen Foley, Sunil Sonwalkar, Jonathon Snook, Lawrence Armstrong, Amanda Beale, Andy Li, Tariq Mahmood, Stephen Lewis, Kevin J. Monahan, Timothy J. McDonald, Gareth T. Jones, John N. Gordon, Nicholas A Kennedy, Sheldon C. Cooper, Gareth J. Walker, James W Hart, Sarah Langlands, Carl A. Anderson, Marcus Harbord, Alistair McNair, Achuth Shenoy, Graham A. Heap, Radhakrishnan Hariraj, Mandy H Perry, Charlie Lees, Shanika de Silva, Christopher J. Hawkey, Loukas Moutsianas, Matthew J Brookes, Christos Tzivinikos, Veena Zamvar, Cathryn Edwards, Claire Bell, Rebecca Saich, Peter M. Irving, Mark S. Smith, Phillip Mayhead, Christopher Macdonald, Dharamveer Basude, Andrew T. Cole, Ailsa Hart, Daniel R. Gaya, Kasamu Dawa Kabiru, Assad Butt, John C Mansfield, John Beckly, Anton V J Gunasekera, Simon Lal, Charles Pj Charlton, Astor Rodrigues, Craig Mowat, Joel Mawdsley, Palani Sathish Babu, John C. Mansfield, Mary-Anne Morris, Senthil V. Murugesan, Dermot P.B. McGovern, Richard Pollok, Franco Torrente, Jeffrey C. Barrett, Aleksejs Sazonovs, Aminda De Silva, George MacFaul, Paul Dunckley, Neeraj Prasad, Zahid Mahmood, Neil P. Shah, Richard Shenderey, Tariq Iqbal, Anjan Dhar, Bruce McLain, James R Goodhand, Anita Modi, Daniel L. Rice, Patrick Goggin, Alka Thakur, Vinod B. Patel, Vishal Kaushik, Scott Levison, Sonia Bouri, Fraser Cummings, Emma Wesley, Anurag Agrawal, Deven Vani, Jimmy K. Limdi, Miles Parkes, David A Elphick, Mark Tighe, Nicholas M. Croft, Charlie W. Lees, Helen Matthews, B K Baburajan, Andrew Bell, Melissa A. Smith, Tariq Ahmad, Stephen Bridger, Mark Tremelling, Matthew W. Johnson, John Fell, Claire Bewshea, Bim Bhaduri, Julie Doherty, Sean Weaver, Ben Colleypriest, Chuka U. Nwokolo, John de Caestecker, Richard K. Russell, Stuart Bloom, Rice, Daniel L [0000-0002-2972-0365], Chanchlani, Neil [0000-0003-0207-6706], McDonald, Timothy J [0000-0003-3559-6660], Anderson, Carl A [0000-0003-1719-7009], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Inflammatory bowel disease, Gastroenterology, Infliximab/immunology, 0302 clinical medicine, Crohn Disease, GWAS, Crohn's disease, Immunogenicity, Hazard ratio, PANTS, Crohn Disease/blood, Middle Aged, Ulcerative colitis, Loss Of Response, 030211 gastroenterology & hepatology, Female, medicine.drug, Adult, medicine.medical_specialty, Heterozygote, Combination therapy, Drug Persistence, HLA-DQ alpha-Chains, 03 medical and health sciences, Young Adult, Adalimumab/immunology, Internal medicine, HLA-DQ alpha-Chains/genetics, medicine, Adalimumab, Humans, Alleles, Gastroenterology & Hepatology, Hepatology, Tumor Necrosis Factor-alpha, business.industry, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Patient Selection, 1103 Clinical Sciences, medicine.disease, Infliximab, 030104 developmental biology, 1114 Paediatrics and Reproductive Medicine, 1109 Neurosciences, business, Genome-Wide Association Study
Abstract: BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.METHODS: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease.RESULTS: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P = 5.88 × 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P = 6.60 × 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57-2.58).CONCLUSIONS: In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.
Published: 2020
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9. Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study

Author: Jennifer A Campbell, Katherine A Francis, Arvind Ramadas, Andrew D Hopper, Matthew Kurien, David S Sanders, Diamond Joy, Hatim Taha, and Sai Lee
Subjects: medicine.medical_specialty, Time Factors, Comorbidity, Gastroenterology, Inflammatory bowel disease, Secondary Care, 03 medical and health sciences, Feces, 0302 clinical medicine, Weight loss, Predictive Value of Tests, Risk Factors, Diabetes mellitus, Internal medicine, Weight Loss, medicine, Odds Ratio, Prevalence, Humans, Enzyme Replacement Therapy, 030212 general & internal medicine, Irritable bowel syndrome, Retrospective Studies, Pancreatic Elastase, business.industry, Odds ratio, Enzyme replacement therapy, Lipase, Clinical Enzyme Tests, medicine.disease, Steatorrhea, Pancreatic Function Tests, medicine.anatomical_structure, Logistic Models, Treatment Outcome, England, Pancreatitis, 030211 gastroenterology & hepatology, Exocrine Pancreatic Insufficiency, medicine.symptom, Pancreas, business, Biomarkers
Abstract: Background & Aims: Pancreatic exocrine insufficiency may be under recognised in gastroenterological practice. We aimed to identify the prevalence of pancreatic insufficiency in secondary care gastroenterology clinics and determine if co-morbidity or presenting symptoms could predict diagnosis. A secondary aim was to assess response to treatment. Methods: A dual centre retrospective analysis was conducted in secondary care gastroenterology clinics. Patients tested for pancreatic exocrine insufficiency with faecal elastase-1 (FEL-1) between 2009 and 2013 were identified in two centres. Demographics, indication and co-morbidities were recorded in addition to dose and response to pancreatic enzyme replacement therapy. Binary logistic regression was used to assess if symptoms or co-morbidities could predict pancreatic insufficiency. Results: 1821 patients were tested, 13.1% had low FEL-1 (
Published: 2016

10. Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study

Author: Chris MacDonald, P T Rajasekhar, Morgan Moorghen, Colin J Rees, Anjan Dhar, James Mason, Brian P. Saunders, Usman Muhammad, Helen C. Hancock, Anthoor Jayaprakash, Matthew D. Rutter, Ana Wilson, Arvind Ramadas, Helen Close, Rebecca Maier, and James E. East
Subjects: Adenoma, medicine.medical_specialty, COLONOSCOPY, Colorectal cancer, Colonoscopy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, COLORECTAL ADENOMAS, Internal medicine, medicine, Humans, Prospective cohort study, COLONIC NEOPLASMS, Narrow-band imaging, medicine.diagnostic_test, business.industry, Endoscopy, medicine.disease, digestive system diseases, Hyperplastic Polyp, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Histopathology, Radiology, business, Colorectal Neoplasms, RC
Abstract: Background Accurate optical characterisation and removal of small adenomas (
Published: 2016

11. Improving Colorectal Adenoma Detection Rate with Endocuff Vision. Results of the Adenoma Randomised Controlled Trial

Author: J Painter, Arvind Ramadas, Zacharias P. Tsiamoulos, Laura J Neilson, Nicola Totton, Brian P. Saunders, Gayle Clifford, Colin J Rees, Thomas J. Lee, Roisin Bevan, Zoe Hoare, Paul Bassett, Matthew D. Rutter, Wee Sing Ngu, and John G Silcock
Subjects: medicine.medical_specialty, Hepatology, Adenoma, business.industry, Gastroenterology, Colorectal adenoma, medicine.disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, Detection rate, business
Published: 2017
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12. PWE-208 How common is pancreatic exocrine insufficiency in primary care?

Author: S Lee, D Joy, Andrew D Hopper, Matthew Kurien, Arvind Ramadas, Jennifer A Campbell, H Taha, David S Sanders, and KA Francis
Subjects: medicine.medical_specialty, business.industry, Pancreatic exocrine insufficiency, Gastroenterology, Primary care, medicine.disease, Symptomatic relief, Coeliac disease, Weight loss, Internal medicine, Diabetes mellitus, medicine, Pancreatitis, medicine.symptom, Intensive care medicine, Exocrine pancreatic insufficiency, business
Abstract: Introduction The prevalence of chronic pancreatitis in post mortem studies is between 6–12%. We previously studied over 1800 all-comers to secondary care gastroenterology and found 14.4% had low faecal elastase-1 (FEL-1) suggestive of exocrine pancreatic insufficiency (EPI). We sought to investigate if there were similar rates in primary care. Method A retrospective analysis of primary care patients tested for EPI between 2009–13 was performed. FEL-1 Results 168 primary care patients and 1887 ssecondary care patients were identified. The mean age in primary care was 59.74 (SD 16.26, 98 female) cf secondary care mean age 51.60 (SD 16.91, 1144 female) p The overall prevalence of EPI in primary care was 20.2% (FEL-1 79.4% (27/34) of primary care patients with FEL-1 Weight loss and steatorrhoea were significantly associated with FEL-1 76.5% (26/34) patients had documented pancreatic enzyme supplementation, of which 80.7% (21/26) reported symptomatic relief. 7.7% reported no benefit and 11.5% were unable to tell. Conclusion This is the first primary care study reporting a prevalence of exocrine pancreatic insufficiency (20.2%). Primary care physicians are correctly identifying patients for testing presenting with weight loss and steatorrhoea, as well as considering the associations of diabetes, coeliac disease and excess alcohol. Imaging and symptomatic benefit (from Creon) supports their diagnosis in almost 60% and 80% respectively. Disclosure of interest None Declared.
Published: 2015
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12 results on '"Arvind Ramadas"'

1. Ondansetron for irritable bowel syndrome with diarrhoea: randomised controlled trial

2. Enhanced neoplasia detection in chronic ulcerative colitis: the ENDCaP-C diagnostic accuracy study

3. 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

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

5. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

6. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study

7. Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial

8. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease

9. Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study

10. Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study

11. Improving Colorectal Adenoma Detection Rate with Endocuff Vision. Results of the Adenoma Randomised Controlled Trial

12. PWE-208 How common is pancreatic exocrine insufficiency in primary care?

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