Danish Society for Gastroenterology and Hepatology's clinical recommendations for colonoscopic surveillance for colorectal dysplasia and cancer in patients with inflammatory bowel disease.

OBJECTIVES: We aimed to produce clinical recommendations for colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases. MATERIALS AND METHODS: The Danish Society for Gastroenterology and Hepatology convened a committee to assess the literature on colorectal cancer in inflammatory bowel diseases and the effectiveness of colonoscopy surveillance, according to the Oxford Centre for Evidence Based Medicine levels of evidence. RESULTS: Clinical recommendations for the colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases were produced. These guidelines cover the risk stratification, entry, and follow-up of patients in the colonoscopy programme, the choice of image-enhanced colonoscopy modality, the investigation and treatment of lesions, and the management of special patient populations in the colonoscopy programme. CONCLUSIONS: Colonoscopic surveillance of inflammatory bowel disease is thought to be associated with a decreased risk of colorectal cancer and colorectal cancer-related mortality. Further evidence regarding the effectiveness of colonoscopic surveillance will contribute to understanding its role in the management of inflammatory bowel diseases. The Danish Society for Gastroenterology and Hepatology clinical guideline will aid gastroenterologists in the risk stratification of patients with inflammatory bowel disease, and the management of colorectal lesions. Gastroenterologists must inform and support patients with inflammatory bowel disease to decide whether to participate in the colonoscopic surveillance programme.

Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases.

BACKGROUND: Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn's disease (CD) are emerging. OBJECTIVE: To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. METHODS: A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. RESULTS: The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non-structuring, non-penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. CONCLUSION: Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.

Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT).

INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.

The Prognostic Value of Pain Phenotyping in Relation to Treatment Outcomes in Patients with Axial Spondyloarthritis Treated in Clinical Practice: A Prospective Cohort Study.

Despite the control of inflammation, many patients with axial spondyloarthritis (axSpA) still report pain as a significant concern. Our objective was to explore the prognostic value of the painDETECT questionnaire (PDQ) in relation to treatment outcomes in axSpA patients treated in clinical practice. AxSpA patients with high disease activity initiating or switching a biological Disease-Modifying Antirheumatic Drug (bDMARD) were eligible. The PDQ score (range: -1 to 38) was used to distinguish participants with nociceptive pain (NcP) mechanisms from participants with a mixed pain mechanism (MP). The primary outcome was the proportion of individuals achieving a 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 12 weeks; logistic regression analysis models were used to determine the prognostic value of the nociceptive pain phenotype. Changes in continuous outcomes such as the Assessment of SpondyloArthritis International Society (ASAS) core outcome domains were analyzed using analysis of covariance (ANCOVA). Health-related quality of life (HR-QoL) was addressed using the Medical Outcomes Study SF-36. During a period of 22 months, 49 axSpA patients were included. Twenty (41%) had an NcP phenotype according to the PDQ score. BASDAI50 responses were reported by 40% (8/20) and 28% (8/29) NcP and MP groups, respectively. However, a prognostic value was not found in relation to the primary outcome (crude odds ratio [95% confidence interval]: 1.75 [0.52 to 5.87]). Across most of the secondary outcomes, axSpA NcP phenotype patients were reported having the most improvements in the HR-QoL measures. These data indicate the influence of personalized management strategies according to patients' pain phenotypes for stratification of axSpA patients in randomized controlled trials.

Do statins protect against upper gastrointestinal bleeding?

AIMS: Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other antithrombotic drugs. METHODS: A population-based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB from a hospital during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by a risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression. RESULTS: The adjusted odds ratios (ORs) associating use of statins with UGB were 0.94 (0.78-1.12) for current use, 1.40 (0.89-2.20) for recent use and 1.42 (0.96-2.10) for past use. The lack of effect was consistent across most patient subgroups, different cumulative or current statin doses and different statin substances. In explorative analyses, a borderline significant protective effect was observed for concurrent users of low-dose aspirin [OR 0.43 (0.18-1.05)]. CONCLUSION: Statins do not prevent UGB, except possibly in users of low-dose aspirin.

Spironolactone use and the risk of upper gastrointestinal bleeding: a population-based case-control study.

AIMS: Recent studies have suggested an increased risk of upper gastrointestinal bleeding (UGB) in spironolactone users. The aim was to confirm the association, identify the risk factors and quantify the absolute risk. METHODS: A population based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression. RESULTS: The adjusted odds ratio (OR) associating current use of spironolactone with UGB was 2.7 [95% confidence interval (CI) 2.2, 3.2]. The risk increased with higher doses of spironolactone (5.4; 3.4, 8.6) for 100-mg tablets. No trend was found with increasing cumulative dose. The strongest association was found among users aged 55-74 years (OR 13.1; 6.5, 26.3). Current use of loop diuretics was also associated with an increased risk of UGB (1.9; 1.7, 2.1). CONCLUSION: The use of spironolactone is associated with increased risk of UGB. The risk increases with higher doses.

Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study.

INTRODUCTION: Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response. METHOD AND ANALYSIS: We will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score. ETHICS AND DISSEMINATION: The study is approved by the Region of Southern Denmark's Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s).

Inadvertent yellow fever vaccination of a patient with Crohn's disease treated with infliximab and methotrexate.

We present a case of a 56-year-old woman with Crohn's disease, treated with methotrexate and infliximab, who inadvertently received yellow fever vaccination (YFV) prior to a journey to Tanzania. She was not previously vaccinated against YF. YFV contains live-attenuated virus, and is contraindicated in patients treated with immunosuppressive drugs. Following vaccination, the patient fell ill with influenza-like illness. Elevated transaminase levels and YF viremia were detected. Despite being immunocompromised, the patient did not develop more severe adverse effects. Neutralising antibodies to YF virus were detected on day 14 following vaccination and remained protective at least 10 months after vaccination. Limited data is available on outcomes of YFV in patients receiving immunosuppressive therapy, including biologics, and we report this case as a reminder of vigilance of vaccine recommendations in this population.

Colonoscopy surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel disease.

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients with IBD is based on a thorough review of existing literature with particular focus on recent studies from Denmark revealing a lower risk of CRC than previously assumed. The overall risk of CRC in the Danish IBD population does not appear to be different from that of the background population; however, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative colitis; and patients with ulcerative colitis as well as Crohn's disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted biopsies of the lesion and adjacent mucosa, instead of conventional colonoscopy with random biopsies. Preferably, the colonoscopy should be performed during clinical remission. If a lesion is detected the endoscopical resectability together with the pathology of the lesion and the adjacent mucosa determine how the lesion should be treated.

[Use of anti-thrombotic agents--monotherapy or combination and risk of upper gastrointestinal bleedings: a population-based case-control study. Secondary publication]. / Brug af antitrombotisk behandling i monoterapi eller kombination og risikoen for øvre gastrointestinal blødning. Et populationsbaseret case-kontrol-studie. Sekundaerpublikation.

The clinical use of anti-thrombotic agents has shifted towards more aggressive therapy and towards regimes with more than one drug. Data on the risk of upper gastrointestinal bleedings (UGB) with combined anti-thrombotic therapy are scarce. In the period 2000 through 2004, 1,443 cases of serious UGB and 57,720 control subjects were identified in Funen County. Anti-thrombotic therapy is becoming increasingly aggressive. Combined anti-thrombotic therapy confers particular risk and is associated with high incidence rates of GI bleeding.

Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study.

OBJECTIVES: To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population. DESIGN: Population based case-control study. SETTING: Funen County, Denmark (population 470,000). SUBJECTS: 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57,720 age and sex matched controls. MAIN OUTCOME MEASURE: Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment. RESULTS: Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population. CONCLUSION: Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.