Ingrid Prytz Berset

Background and Aims: Monoclonal antibodies against tumor necrosis factor (anti-TNF) are effective agents in the treatment of moderate-to-severe ulcerative colitis (UC). It is unclear whether such treatment can safely be discontinued without relapse. This study aimed to identify biomarkers to predict which patients can successfully stop anti-TNF treatment, and to increase our understanding of the pathogenesis of relapse after withdrawal and flare on continued therapy. Methods: We analyzed longitudinal bulk RNA-sequencing data derived from rectal mucosal biopsies from 163 patients in the BIOSTOP study collected at baseline, after 2 years (end of study), and at flares or relapse points. Results: In this cohort, pre-withdrawal transcriptomic profiles did not distinguish patients who later relapsed from those who remained in long-term remission. Longitudinal analysis of patients who relapsed or flared were both characterized by inflammatory gene expression profiles (eg, CXCL9, CXCL10, OSMR, SELE) and changes in cell-type composition typical for active UC (eg, monocytes/macrophages and THY1+ FAP+ PDPN+ activated fibroblasts). Both groups showed enrichment of T-cell-associated transcriptional signatures, including CD8 T-cell-related genes and IL-17-associated pathways. Additionally, both patient groups showed increased expression of targets of alternative therapeutic agents, suggesting potential treatment options for specific patient subgroups. Conclusions: Our findings provide insights into the inflammatory mechanisms driving relapse after anti-TNF withdrawal and flare on continued treatment. The dataset offers a valuable resource for future research to improve personalized treatment strategies in UC.

Background and Aims: Anti-tumour necrosis factor (anti-TNF) treatment is effective in ulcerative colitis (UC). Optimal treatment duration is uncertain. This trial studies outcome after anti-TNF withdrawal compared to maintenance treatment in UC. Methods: In this prospective, multicentre, randomized, controlled, open-label non-inferiority study, patients in deep clinical, biochemical and endoscopic remission were randomized 1:1 to anti-TNF withdrawal or maintenance treatment. Primary endpoint was endoscopically confirmed remission (Mayo Endoscopic Score 0 or 1) after two years, including UC flares treated with anti-TNF, or non-biologic agents. Secondary endpoints were clinical remission, UC flare rate and treatment response. We needed 170 participants to show non-inferiority with a 15% margin. Results: Between June 2017 and December 2021, 172 UC patients from 19 Norwegian hospitals were randomized; 86 in each group. The per-protocol population was 163 patients. Nine patients were excluded due to consent withdrawal or protocol violation. Eighty percent (66/82) of anti-TNF withdrawal and 96% (78/81) of maintenance patients were in endoscopic remission after 2 years. UC flares occurred in 52% (45/86) of withdrawal and 12% (10/86) of maintenance patients. Anti-TNF retreatment was successful in 74% (20/27). Conclusion: Two years after anti-TNF withdrawal in UC patients in deep remission, endoscopically confirmed remission rate was significantly lower compared to maintenance treatment. Non-inferiority could not be proven. UC flare rate after anti-TNF withdrawal was high, but most were successfully treated. The majority did not receive AZA. Importantly, 48% of anti-TNF withdrawal patients remained in steroid-free remission. No significant predictors for UC activity after anti-TNF withdrawal were identified. Trial registration: ClinicalTrials.gov (registration number NCT03011268), and EudraCT (registration number 2016-001409-18)

Summary: Background: Case series suggest a possible association between bariatric surgery and incident IBD.Aim: The aim of this study was to evaluate the association between bariatric surgery and new‐onset IBD.Methods: We first conducted a multi‐institutional case series of patients with a history of IBD and bariatric surgery. We next conducted a matched case‐control study using medical and pharmacy claims from 2008 to 2012 in a US national database from Source Healthcare Analytics LLC. Bariatric surgery was defined by ICD‐9 or CPT code. Bariatric surgery was evaluated as recent (code in database timeframe), past (past history V code) or no history. Conditional logistic regression was used to estimate odds ratios (OR) and 95% CI for new‐onset IBD, CD and UC.Results: A total of 15 cases of IBD (10 CD, 4 UC, 1 IBD, type unclassified) with a prior history of bariatric surgery were identified. Most cases were women, had Roux‐en‐Y surgery years prior to diagnosis and few IBD‐related complications. A total of 8980 cases and 43 059 controls were included in our database analysis. Adjusting for confounders, a past history of bariatric surgery was associated with an increased risk of new‐onset IBD (OR 1.93, 95% CI 1.34‐2.79). However, patients who had recent bariatric surgery did not appear to be at shorter term risk of IBD (OR 0.94, 95% CI 0.58‐1.52).Conclusion: New‐onset IBD was significantly associated with a past history of bariatric surgery. This potential association needs to be confirmed in future prospective studies.

Clinically effective therapies now exist for remission maintenance in both ulcerative colitis (UC) and Crohn’s Disease (CD). For each major class of IBD medications (5-aminosalicyclates, immunomodulators and biologic agents), used alone or in combination, there is a risk of relapse following reduction or stopping of treatment. A consensus expert panel convened by the European Crohn’s and Colitis Organisation (ECCO) reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized and shared decision making with the patient should take place.

Background and aim: Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aims of the present study were to determine the prevalence of vitamin D deficiency and to identify clinical and epidemiological variables associated with vitamin D deficiency in an outpatient population with IBD. Methods: Participants were recruited from nine hospitals in the southeastern and western regions of Norway as part of an observational, multicentre study from March 2013 to April 2014. Clinical and epidemiological data were collected by interview and from medical records. All analyses of serum 25-hydroxyvitamin D (25-OH-D) were performed in the same laboratory. Results: In total, 49% (200/408) of the patients had a 25-OH-D concentration 100 mg/kg. In patients with CD, there were significantly more relapses during the previous year in patients with vitamin D deficiency. Conclusions: Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.

Background and aims Quality of care (QoC) has gained increased attention in IBD. A better QoC has, historically, been linked to improved treatment outcomes. Even so, factors of equal importance to patients may be quality of life (QoL), patient–physician communication and access to care. Recent surveys suggest that IBD care in Europe is suboptimal. Methods Patients were recruited from nine hospitals in the south-eastern and western part of Norway as a part of an observational, multicenter study In addition to clinical and socio-demographic factors; a purposely designed 26 item questionnaire was used to quantify aspects related to IBD care, including QoC. Moreover, the Fatigue Questionnaire (FQ) was used to investigate fatigue. Results In total, 411 patients were included. Of these, 231 were diagnosed with CD and 180 with UC. Furthermore, 86.1% (354/411) were satisfied with the quality of IBD follow-up and only 4.1% (17/411) were dissatisfied. Most dissatisfaction was related to: lack of focus on personal relations (18.2%), HRQoL (15.1%), general practitioner knowledge of IBD (13.9%), ability to talk about important topics (7.8%), and hospital discharge communication (9.4%). Higher age and longer disease duration was associated with improved QoC scores in both UC and CD. Fatigue was associated with decreased QoC scores in both diagnoses. Conclusions Patients are satisfied with quality of care in IBD. However, communication seems to be an important area of improvement – not only related to patient–physician communication, but also to transitional communication between different health-care levels.

Background: Colonoscopy requires insufflation of gas for visualization of the bowel wall. Worldwide, this is usually done using air. The aim of the present study was to assess the risk of postcolonoscopy incontinence, and to investigate whether insufflation of CO₂ instead of air may reduce this risk, since it is easily absorbed through the bowel mucosa. Methods: This is a prospective multicenter study of colonoscopy patients undergoing bowel insufflation using air or CO₂. A successive series of colonoscopies were reported to a national quality assurance program in Norway between January and December 2009 from 21 endoscopy centers with varying insufflation practices. The study comprised 7812 patients aged 18 years or older who were referred for outpatient colonoscopy. Of these, 5015 underwent colonoscopy performed using air and 2797 colonoscopy using CO₂ insufflation. Results: Patient-reported incontinence up to 24 h after colonoscopy was compared using binary logistic regression analysis for the type of gas used for insufflation. The air and CO₂ patient groups were comparable with regard to age, sex, indication for colonoscopy, and sedation practice. Incontinence was reported by 336 out of 7812 patients (4.3 %). Incontinence was significantly less frequent in the CO₂ group than in the air group [2.1 % versus 5.5 %; adjusted odds ratio (OR) 0.38; 95 %CI 0.28 – 0.50; P < 0.001]. Female patients had a higher risk of incontinence than men (adjusted OR 1.77; 95 % CI 1.39 – 2.24; P < 0.001). Conclusion: About every 20th patient undergoing colonoscopy using standard air insufflation experiences postexamination incontinence. This proportion can be reduced by 60 % by converting from air insufflation to insufflation with the absorbable CO₂.

Background: Usually, colonoscopy insertion is performed by the colonoscopist (one-person technique). Quite common in the early days of endoscopy, the assisting nurse is now only rarely doing the insertion (two-person technique). Using the Norwegian national endoscopy quality assurance (QA) programme, Gastronet, we wanted to explore the extent of two-person technique practice and look into possible differences in performance and QA output measures. Methods: 100 colonoscopists in 18 colonoscopy centres having reported their colonoscopies to Gastronet between January and December 2009 were asked if they practiced one- or two-person technique during insertion of the colonoscope. They were categorized accordingly for comparative analyses of QA indicators. Results: 75 endoscopists responded to the survey (representing 9368 colonoscopies) - 62 of them (83%) applied one-person technique and 13 (17%) two-person technique. Patients age and sex distributions and indications for colonoscopy were also similar in the two groups. Caecal intubation was 96% in the two-person group compared to 92% in the one-person group (p < 0.001). Pain reports were similar in the groups, but time to the caecum was shorter and the use of sedation less in the two-person group. Conclusion: Two-person technique for colonoscope insertion was practiced by a considerable minority of endoscopists (17%). QA indicators were either similar to or better than one-person technique. This suggests that there may be some beneficial elements to this technique worth exploring and try to import into the much preferred one-person insertion technique.