Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

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.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Breath volatile analysis from patients diagnosed with harmful drinking, cirrhosis and hepatic encephalopathy: A pilot study

Hepatic encephalopathy (HE) is a neuropsychiatric state potentially complicating cirrhosis following the accumulation of toxic compounds that cross the blood-brain barrier and affect brain function; the compounds may undergo alveolar gas exchange and be partially excreted by exhalation. Thus breath analysis as a non-invasive means of diagnosing HE, cirrhosis and harmful drinking was investigated in a pilot study. One litre samples of breath were collected from patients with alcohol-related cirrhosis (n = 34) with HE (n = 11) and without HE (n = 23), non-alcoholic cirrhosis without HE (n = 13), harmful drinkers without cirrhosis (n = 7), and healthy controls (n = 15) in a hospital setting. Breath compounds trapped on adsorbent tubes were released via thermal desorption and analysed by gas chromatography mass spectrometry for separation and detection. Multivariate discriminant analysis was used to identify volatile organic compounds to differentiate patients according to disease status and build models for disease classification. HE was correctly identified in 90.9 % of alcoholic cirrhotic patients and liver cirrhosis in 100 % of alcoholic patients. In patients without clinical HE, alcohol was correctly predicted as the cause of cirrhosis in 78.3 % of patients and non-alcoholic causes of cirrhosis were correctly determined in 69.2 %. Non-alcoholic cirrhosis, alcoholic cirrhosis, and harmful drinking could be discriminated from healthy controls with a sensitivity of 92.3, 97.1 and 100 %, respectively. Breath volatile analysis has the potential to aid the diagnosis of HE and a range of liver disorders. © 2013 Springer Science+Business Media New York

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

BackgroundThere 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. MethodsThe 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. FindingsWe 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. InterpretationThe 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

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

BackgroundTranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.MethodsWe did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.FindingsBetween July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).InterpretationWe found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.</div