Gøri Perminow

Background: This study aimed to compare the proportion of Crohn’s disease (CD) and ulcerative colitis (UC) patients receiving work disability (WD) benefits with the corresponding proportion in the background population at diagnosis and after 1 year, and to assess associations between selected variables and WD. Methods: Adults from a population-based inception cohort with WD data at diagnosis and/or 1-year follow-up were included. WD was defined as receiving work assessment allowance (AAP) or disability pension (DP). Relative risks (RRs) for AAP and DP were calculated vs. national registry proportions stratified by age and sex, overall RRs were age standardized. Multivariable logistic regression assessed associations between WD and selected variables. Results: At diagnosis, risk of AAP was increased for UC (RR, 1.5; 95% confidence interval [CI], 1.1-2.1) and CD patients between 30-39 years old (RR, 2.8; 95% CI, 1.1-5.8). AAP risk was increased at 1-year for both UC (RR, 1.6; 95% CI, 1.1-2.4) and CD (RR, 3.6; 95% CI, 2.4-5.2). DP risk was comparable with the background population. Higher general self-efficacy and health-related quality of life were associated with lower odds of WD, whereas disease-activity variables were not. Older age, comorbidities, and lower education were also associated with increased odds of WD in UC. Conclusions: After 1 year, patients with UC and CD had increased risk of AAP. Lower general self-efficacy and poorer health-related quality of life were associated with higher WD, suggesting a potential window for targeted interventions to reduce AAP and prevent or delay DP.

Background and Aim: Despite the well-established involvement of the gut microbiome in inflammatory bowel disease (IBD), less is known about how the gut microbiome changes over time and how it varies with clinical disease activity and fecal calprotectin (f-calprotectin). To address this gap, we utilized samples from the population-based inception cohort of the Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) study. Methods: Data and stool samples from study participants with IBD and symptomatic controls were collected at diagnosis and after 3, 6, and 12 months. Microbiome profiling of stool samples was performed targeting the V3-V4 region of the 16S rRNA gene, and a consensus-based approach of mixed models was employed for the longitudinal microbiome analysis. Results: We included 1251 samples from 744 patients with ulcerative colitis, 618 samples from 356 patients with Crohn’ s disease and 266 samples from 164 symptomatic non-IBD controls. In the IBD population, we observed that levels of f-calprotectin decreased over time, as did the patient-reported disease activity (P < .001). Distinct changes in the gut microbiome of IBD patients were observed throughout the first year, such as increased alpha diversity (P < .001) and significant taxonomic changes. Notably, there was no covariation between the changes in alpha diversity and f-calprotectin or symptom score. Conclusion: The gut microbiome during the first year after IBD diagnosis showed changes that paralleled inflammation and clinical disease activity, albeit without covariation, suggesting that there may be a disease-driving impact of gut microbiome independent of inflammation and inflammation-driven symptoms.

Background: Inflammatory bowel diseases (IBDs) are complex conditions marked by chronic inflammation in the gastrointestinal tract. Traditional classification separates IBD into Crohn’s disease and ulcerative colitis, but this division may not fully capture disease heterogeneity. Here, we examine whether microbiome-driven subtyping can describe novel clinical IBD phenotypes. To achieve this, we applied unsupervised clustering to fecal microbiota profiles from the population-based Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) cohort. Methods: A Gaussian Mixture Model (GMM) was used to cluster participants with IBD based on microbiome composition and examine associations between clusters and clinical outcomes, including inflammatory markers and disease severity during the first year after inclusion. Results: Three microbiome-based clusters were identified: CLO (dominated by Clostridia UCG-014), ALF (Agathobacter, Lachnoclostridium, and Faecalibacterium), and RUM (Ruminococcus gnavus). Participants in the RUM cluster had a higher risk of future severe disease than those in the CLO cluster, even among participants with remission-to-mild disease at inclusion (21% vs. 6%, P < 0.00001). This association could not be explained by antibiotic use or baseline disease severity. Cluster membership alone performed comparably to fecal calprotectin in distinguishing severe disease, and a combined model significantly improved accuracy (P < 0.0001). Conclusion: Our findings demonstrate a connection between microbiome composition and the risk of severe disease development, which is partly independent of inflammation levels at the time of sampling. Microbiome-informed subgrouping could lead to more personalized treatment strategies. Further validation is needed to determine the clinical utility of these clusters.

Objectives: Diagnostic delay is common in pediatric inflammatory bowel disease (PIBD), and fecal calprotectin (FCP) is often limited by challenges with sample collection. Therefore, we aimed to identify and validate a blood‐based diagnostic protein signature of PIBD. Methods: Proteins were analyzed using proximity extension assay in plasma samples from treatment‐naïve pediatric patients in a Swedish inception cohort referred for suspected inflammatory bowel disease (IBD) and validated in an independent Norwegian population‐based pediatric inception cohort. Diagnostic performance was estimated by the area under the curve (AUC) with 95% confidence intervals (CIs). Results: The discovery cohort included 58 patients with PIBD and 36 symptomatic controls without evidence of IBD, while the validation cohort consisted of 79 patients with PIBD and 37 symptomatic controls. In total, 154 proteins were examined. Univariable analyses identified 26 differentially regulated proteins for PIBD versus symptomatic controls in the discovery cohort ( q < 0.05), whereas 29 proteins were differentially regulated in the validation cohort. Using regularized logistic regression, we identified a diagnostic model of 31 proteins that differentiated PIBD from symptomatic controls in the discovery cohort (AUC = 0.83; 95% CI: 0.74–0.90). The protein signature was further reduced to a clinically relevant biomarker consisting of high‐sensitivity C‐reactive protein (hsCRP) and seven other proteins with diagnostic capacity (AUC = 0.85, 95% CI: 0.78–0.92) outperforming hsCRP in the validation cohort ( p = 0.006). Conclusions: We identified and validated a blood‐based protein signature for PIBD with superior diagnostic performance compared to hsCRP. Given the challenges of fecal sample collection, further assay development may enable integration of these biomarkers into diagnostic pathways for PIBD. Trial Registration: ClinicalTrials.gov identifier: NCT02727959.

Identifying patients at risk of developing severe inflammatory bowel disease (IBD) can aid treatment decisions. However, predicting disease course remains challenging. We aimed to identify predictive factors associated with severe disease course in the first year after IBD diagnosis. Newly diagnosed adult (≥18 years) patients with IBD were recruited from a population-based inception cohort (IBSEN III study). Preselected baseline factors were tested for associations with severe disease course, defined as IBD-related hospitalisation, surgery, treatment with ≥2 steroid courses, >2 biologics and/or new event of complication (stricture, fistula, abscess only applicable Crohn's disease (CD)). From a best fitted multivariable logistic regression model stratified by diagnosis and age (18-40/>40 years), probability of severe disease for given combinations of predictive factors was summarised in prediction matrices. At one-year follow-up, 90/559 (16%) patients with ulcerative colitis (UC) and 74/312 (24%) with CD had severe disease. Treatment with systemic steroids, vitamin D deficiency, Simple Clinical Colitis Activity Index >2, and hypoalbuminemia at diagnosis were all significantly associated with severe disease in UC patients. CD patients with stricturing or penetrating disease behaviour, systemic steroids and hypoalbuminemia at diagnosis were associated with severe disease course. The least favourable combination of these factors increased the probability of severe disease from 3% (95%CI[0-5%]) to 72% (95%CI[66-79%]) for UC and from 8% (95%CI[3-13%]) to 88% (95%CI[84-93%]) for CD. Our study identified predictive factors associated with severe disease the first year after diagnosis. The probability of severe disease summarised in matrices enables easy risk stratification.

Background and Aims: The emergence of biologic therapy has coincided with a decline in surgery rates for Crohn’s disease (CD). This study aims to describe the disease course, including intra-abdominal surgery rates, biologic therapy use, and variables associated with biologic therapy initiation in a cohort of newly diagnosed CD patients. Methods: The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study. From 2017 to 2019, newly diagnosed inflammatory bowel disease patients were included for prospective follow-up. The present study included CD patients ≥ 18 years. Clinical, endoscopic, and demographic data were collected at diagnosis and 1-year follow-up. Data were analyzed by using the Kaplan–Meier method and regression analyses. Results: In total, 424 CD patients (median age 37.0 years (range 18-80), female 55.0%) were included. At diagnosis, 50.5% presented with ileal disease and 80.7% with inflammatory behavior. Within a 1-year follow-up, 39.6% of patients received their first biologic therapy and 5.2% required intra-abdominal surgery. Systemic steroid treatment, CRP ≥ 5.0 mg dL−1, Harvey–Bradshaw Index score > 4, ileocolonic disease and penetrating disease behavior at diagnosis were independently associated with increased risk of initiation of biologic therapy, while age > 40 years was associated with decreased risk. Conclusion: A high proportion of patients had ileal disease and inflammatory behavior at diagnosis. Still, nearly 40% started biologic therapy within the 1-year follow-up, while only 5% required intra-abdominal surgery.

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.

Fecal (f-) calprotectin is demonstrated to predict forthcoming flares in Inflammatory Bowel Disease (IBD). Predictive value in newly diagnosed IBD is scarcely studied. The aim of this study was to investigate if high or low f-calprotectin at time of diagnosis of IBD was associated with need of steroids during first year of disease in a population-based inception cohort study (IBSEN III). Newly diagnosed IBD patients >18 years, enrolled from the South-Eastern Health Region of Norway in the period of 2017–2019, were studied. Age, gender, smoking status, CRP and level of f-calprotectin were registered at diagnosis. At one-year follow-up, oral and intravenous (IV) steroid use during first year of disease were registered. Associations between high levels of f-calprotectin (≥ 500 mg/kg) at diagnosis and steroid use were tested using logistic regression analyses. A p-value of 0.05 was considered statistically significant. At baseline, 352 adult patients with Crohn’s disease (CD) and 702 patients with ulcerative colitis (UC) provided samples for f-calpotectin and were included in this study. Steroid use (both IV and oral) was associated with higher levels of f-calprotectin. When adjusted for CRP, age, gender and smoking status, the association remained statistically significant for oral steroid use (CD: OR=2.21, 95%CI [1.25; 3.93], p=0.007. UC: OR=1.87, 95%CI [1.26;2.78], p=0.002), however not for IV steroid use. High level of f-calprotectin at time of diagnosis is associated with oral steroid use during the first year of disease for patients with IBD.

Purpose: Imbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-naïve IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes. Patients and methods: Fecal samples were collected from 235 children below 18 years of age. Eighty children had Crohn’s disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map™ technology at diagnosis and after therapy in IBD patients. Results: Bacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (PPrevotella was more abundant in patients (PRuminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (PMycoplasma hominis abundance (PPPFaecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (PConclusion: Fecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individualization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing.

Pediatric Crohn's disease (CD) is often debilitating, with upper gastrointestinal (GI) involvement and complications over time. Treatment with tumor necrosis factor (TNF) blockers can induce and maintain remission. We wanted to evaluate the outcome of patients medically treated for CD to investigate whether clinical, endoscopic and biochemical factors at diagnosis are associated with the early initiation of treatment with the TNF blocker infliximab. Patients aged <18 years, diagnosed with CD were characterized according to the Porto criteria, with endoscopy, magnetic resonance imaging and biochemical tests before individual treatment. They were followed prospectively until a prescheduled examination within 2 years. Thirty-six pediatric patients were included, 18 (50%) received infliximab. Infliximab-treated patients had shorter disease duration, more upper GI involvement (p = 0.03) and higher median C-reactive protein (CRP) (28 vs. 7.5 mg/l, p = 0.02), erythrocyte sedimentation rate (ESR) (32 vs. 18 mm/h, p = 0.01) and fecal calprotectin (1506 vs. 501 mg/kg, p = 0.01) levels. Infliximab treatment was well tolerated, and 15/18 of patients achieved clinical remission. At follow-up, 11/17 in the infliximab group and 8/13 in the non-infliximab group achieved ileocolonic mucosal healing. A majority in the infliximab group had a marked reduction of CD-specific upper GI lesions but persistence of unspecific upper GI inflammation at follow-up. High levels of inflammatory markers and upper GI lesions were associated with initiation of infliximab treatment. A substantial proportion of patients still had unspecific lesions in the upper GI tract regardless of treatment. Future studies must clarify the prognostic role of persistent upper GI-involvement despite mucosal healing in the ileocolon.