Jørgen Jahnsen

• Lindstrøm, Jonas Christoffer; Gjerdrum, Hilde Synnøve Vollan; Brynildsrud, Ola Brønstad; Tannæs, Tone Møller; Kristoffersen, Anja Bråthen & Ricanek, Petr [Vis alle 17 forfattere av denne artikkelen] (2026). Exploring alterations in the gut resistome in medically treated inflammatory bowel disease patients. BMC Microbiology. 26, s. 1–13. doi: 10.1186/s12866-026-05101-9. Fulltekst i vitenarkiv
• Berset, Ingrid Prytz; Lerang, Frode; Moum, Bjørn Allan; Jahnsen, Jørgen; Grimstad, Tore Bjørn & Kristensen, Vendel Ailin [Vis alle 26 forfattere av denne artikkelen] (2026). Anti-TNF withdrawal or long-term treatment in ulcerative colitis (BIOSTOP): a multicentre open label, randomized controlled trial. Journal of Crohn's and Colitis. ISSN 1873-9946. 20(8). doi: 10.1093/ecco-jcc/jjag110. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Holly, Teresa; Brun, Marthe Kirkesæther; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Sexton, Joseph & Gehin, Johanna [Vis alle 15 forfattere av denne artikkelen] (2026). Cost-effectiveness of proactive therapeutic drug monitoring of maintenance infliximab treatment in patients with immune-mediated inflammatory diseases: results from a randomised controlled trial. RMD Open. 12(1), s. 11–11. doi: 10.1136/rmdopen-2025-006329. Fulltekst i vitenarkiv
• Mahdy, Aya K. H.; ElAbd, Hesham; Kokubun, Érika Endo; Kriukova, Valeriia; Pesesky, Mitchell & May, Damon H. [Vis alle 24 forfattere av denne artikkelen] (2026). Multi-centered T cell repertoire profiling identifies alterations in the immune repertoire of individuals with inflammatory bowel disease across different disease stages. Genome Medicine. 18. doi: 10.1186/s13073-025-01575-w. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Inflammatory bowel disease (IBD) is an incurable immune-mediated inflammatory disease, affecting the gut with a high rate of primary- and secondary- loss-of-response to therapy. By investigating the T cell receptor repertoire of individuals with IBD, novel therapeutic and preventive strategies can be identified, and a better understanding of IBD can be obtained. Methods To identify and validate T cell clonotypes implicated in the pathogenesis of IBD, we profiled the T cell receptor alpha (TRA) repertoire of three cohorts containing treatment-naive, treated individuals, and individuals living with the disease for >20 years, resulting in an exhaustive dataset containing the TRA repertoire of 1,732 individuals. Results Using the generated datasets, we were able to replicate previous findings describing the expansion of Crohn’s-associated invariant T (CAIT) cells in individuals with Crohn’s disease (CD) in the three cohorts. Using a hypothesis-free statistical testing framework, we identified clonotypes that were associated with the disease at its different stages, e.g., at the time of diagnosis and decades post-diagnosis. By conducting a meta-analysis across the three cohorts, we were able to identify a set of clonotypes that were associated with the disease regardless of its stage. We validated our findings in a previously published independent test dataset from a German cohort, showing the robustness of the identified clonotypes. Conclusions The identified clonotypes are novel therapeutic targets to treat IBD, for example, through targeted depletion. By identifying antigens recognized by these T cells, a better understanding of the etiopathology of IBD, particularly CD, can be obtained.

• Jahnsen, Marte Eide; Detlie, Trond Espen; Eide, Geir Egil; Moum, Bjørn Allan; Reime, Marit Hegg & Jahnsen, Jørgen (2026). High-dose intravenous iron improves quality of life in patients with inflammatory Bowel disease and iron deficiency. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 61(2), s. 192–200. doi: 10.1080/00365521.2025.2608181. Fulltekst i vitenarkiv Vis sammendrag

  Background Iron deficiency is common in patients with inflammatory bowel disease (IBD) and may lead to a variety of distressing symptoms negatively impacting quality of life. Aims This prospective observational cohort study aimed to assess quality of life, measured using the Short Form-36 (SF-36) questionnaire before and after treatment with high-dose intravenous iron in patients with IBD and iron deficiency. Materials and methods Over a 15-month period, 130 patients with a well-established diagnosis of IBD (either ulcerative colitis (UC) or Crohns disease (CD)) and confirmed iron deficiency were consecutively assessed for study eligibility at two university hospitals in South-Eastern Norway. Of these, 112 patients were included in the per protocol set. Demographic characteristics were recorded at study inclusion. Clinical, and biochemical variables, as well as SF-36 questionnaires were collected just before and 5–7 weeks after treatment with intravenous iron. Results An improvement was observed in six of the eight SF-36 domains six weeks after treatment with intravenous iron. Females had lower scores compared to males at both visits, but there were no differences between UC and CD patients. Both sexes and the two diagnoses had a significant increase in vitality scores. Haemoglobin level was a significant predictor for improvement of quality of life. Conclusions Treatment with high dose intravenous iron improves quality of life in IBD patients and iron deficiency and particularly in those with anaemia. The most significant improvements were observed in vitality and energy levels, suggesting a clinically meaningful change.

• Ferrante, Marc; Peyrin-Biroulet, Laurent; Arkkila, Perttu; Armuzzi, Alessandro; Colombel, Jean Frédéric & Danese, Silvio [Vis alle 17 forfattere av denne artikkelen] (2025). Treatment discontinuation rates due to lack of efficacy through 1 year of maintenance treatment with vedolizumab or subcutaneous infliximab in patients with inflammatory bowel disease: a systematic literature review and meta-analysis. Therapeutic Advances in Gastroenterology. ISSN 1756-283X. 18. doi: 10.1177/17562848251383767. Fulltekst i vitenarkiv Vis sammendrag

  Background: Infliximab (IFX) and vedolizumab (VDZ), frequently used biologics in inflammatory bowel disease (IBD), are available as intravenous (IV) and subcutaneous (SC) formulations; however, comparative data are limited. Objectives: To compare the rates of discontinuation due to lack of efficacy during maintenance treatment with infliximab (subcutaneous) and vedolizumab (intravenous and subcutaneous) in patients with moderate-to-severe IBD. Design: Systematic literature review and meta-analysis. Data sources and methods: Three medical databases, PubMed, Embase, and the Cochrane Library, were systematically searched from January 2010 to May 2024 to identify phases I–III randomized controlled trials. The primary outcome was discontinuation of study drug due to lack of efficacy (per definitions used in the included studies) during maintenance treatment (PROSPERO number CRD42023438330). Rates of discontinuation due to adverse events during maintenance treatment were examined in additional exploratory analyses. Results: We identified three eligible clinical trials in IBD for subcutaneous infliximab (591 patients) and five for vedolizumab (intravenous and subcutaneous formulations; 2117 patients). Rates of discontinuation due to lack of efficacy (per individual study definition) were significantly lower in patients treated with subcutaneous infliximab (0.05 (95% confidence interval (CI): 0.03, 0.06)) than in patients treated with vedolizumab (0.29 (95% CI: 0.20, 0.38)); rates remained significantly lower with subcutaneous infliximab versus vedolizumab, respectively, in the subgroups of patients with Crohn’s disease (0.05 (95% CI: 0.02, 0.07) vs 0.37 (95% CI: 0.27, 0.47)) or ulcerative colitis (0.05 (95% CI: 0.02, 0.07) vs 0.24 (95% CI: 0.11, 0.36)). Rates of discontinuation due to adverse events were lower in subcutaneous infliximab-treated patients (0.04 (95% CI: 0.02, 0.05) than in vedolizumab-treated patients (0.08 (95% CI: 0.05, 0.11)). Conclusion: In this meta-analysis, rates of discontinuation due to lack of efficacy during maintenance treatment were lower with subcutaneous infliximab than with vedolizumab (intravenous and subcutaneous formulations) in patients with moderate-to-severe IBD.

• Romstad, Katrine Kauczynska; Thomas, Owen Matthew Truscott; Søberg, Taran; Detlie, Trond Espen; Ricanek, Petr & Jahnsen, Marte Eide [Vis alle 8 forfattere av denne artikkelen] (2025). High consumption of risk medication and underutilization of proton pump inhibitors among patients with upper gastrointestinal bleeding due to peptic ulcers and erosions (BLUE study). Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 61(1), s. 44–52. doi: 10.1080/00365521.2025.2594780. Fulltekst i vitenarkiv Vis sammendrag

  Background Antiplatelet and anticoagulant therapy are associated with a significant risk of upper gastrointestinal bleeding (UGIB), as is the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant treatment with proton pump inhibitors (PPIs) has been shown to reduce the risk of this complication. Aims To compare the use of risk medications and PPIs in a cohort of adult patients with bleeding peptic ulcers or erosions in the stomach or duodenum with the background population. Materials and methods We performed a prospective observational study including 543 patients with endoscopically verified bleeding ulcers and/or erosions at two large hospitals in Norway. Information on risk medications taken prior to study enrolment was collected prospectively through structured interviews with patients and with the review of their medical records, whereas for the background population the information was obtained from The Norwegian Prescription Database (NorPD). Results Overall, 434 (80%) of the patients used risk medications, compared to 34% in the background population (p < 0.001). Only 39 (8.9%) of the patients received PPIs as co-medication, and 150 (34.6%) tested positive for Helicobacter pylori (H. pylori) infection. Conclusions Among patients with bleeding ulcers and erosions, we found a high prevalence of risk medication use and an underutilization of prophylactic PPIs. H. pylori infection appears to play a minor role. Clinical trial registration Bleeding Ulcer and Erosions Study “BLUE Study”, ClinicalTrials.gov Identifier: NCT03367897.

• Vatn, Simen Svendsen; Hansen, Simen Hyll; Tannæs, Tone Møller; Brackmann, Stephan Andreas; Olbjørn, Christine & Bergemalm, Daniel [Vis alle 17 forfattere av denne artikkelen] (2025). Microbial Patterns in Newly Diagnosed Inflammatory Bowel Disease Revealed by Presence and Transcriptional Activity - Relationship to Diagnosis and Outcome. Clinical and Experimental Gastroenterology. 18, s. 103–119. doi: 10.2147/CEG.S504459. Fulltekst i vitenarkiv Vis sammendrag

  Background: As part of the IBD Character initiative, we examined an inception cohort and investigated mucosal microbiota composition and transcriptional activity in relation to clinical outcomes. Methods: A cohort of 237 individuals were included from five countries: Crohn’s disease (CD, n = 72), ulcerative colitis (UC, n = 57), symptomatic non-IBD controls (SC, n = 78) and healthy controls (HC, n = 30). Rectal/colonic biopsies were obtained at inclusion, and DNA and RNA were extracted from the same biopsy and examined by sequencing the 16S rRNA V4 region. Results: Beta diversity measurements separated IBD from both HC and SC. IBD and SC exhibited reduced intra-individual diversity compared with HC. When comparing taxonomy at DNA and RNA level, six bacteria were found to differ in abundance and/or transcriptional activity between IBD and symptomatic control, while there were 14 and three between symptomatic control and CD and UC, respectively. A limited number of bacterial taxa were responsible for the largest difference between presence and activity, separating patients and controls. Multiple bacterial taxa were associated with treatment escalation in both UC and CD. Machine-learning models separated IBD from symptomatic controls and treatment escalators from non-escalators (AUC > 0.8). However, the differential effects were mainly driven by clinical biomarkers, such as f-calprotectin, s-albumin, and b-hemoglobin. Conclusion: Differences between presence and transcriptional activity were found among multiple taxa when assessing 16S rRNA at DNA and RNA level. Symptomatic controls were more similar to the IBD patients compared to HC. The analyses suggest that the mucosal microbiota carries a moderate diagnostic and predictive potential, outcompeted by f-calprotectin.

• Detlie, Trond Espen; Burisch, Johan; Jahnsen, Jørgen; Bonderup, Ole; Hellström, Per M. & Lindgren, Stefan [Vis alle 7 forfattere av denne artikkelen] (2025). Iron deficiency should not be accepted in patients with inflammatory bowel disease–a Scandinavian expert opinion. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 60(5), s. 430–438. doi: 10.1080/00365521.2025.2487907. Fulltekst i vitenarkiv Vis sammendrag

  Aim In this paper, we aim to explain the reason why iron deficiency (ID) is common in patients with inflammatory bowel disease (IBD), how to better apply diagnostic tools to uncover the state of ID as well as how to interpret the results, and not least, how to treat ID in this group of patients. Methods This article is an expert review and opinion paper on a topic that is too often forgotten in clinical practice. We have not performed a systematic review, but we present the most important research allocated to the topic to substantiate an expert opinion. Results This position paper summarises the pathophysiology of ID and gives recommendations on the monitoring and treatment of ID in IBD. ID with or without concurrent anaemia (IDA) is the most common systemic complication in patients with IBD, related to both disease activity and severity. It has consequences both for health-related quality of life and future course of disease of the IBD patient. Intravenous iron is an efficacious and well tolerated, but still underused, therapy for ID and IDA. Iron deficiency should be treated before symptoms of anaemia appear and quality of life is impacted. However, there is still limited awareness of how to detect and treat ID in clinical practice. Uncertainty regarding which diagnostic tests to use and how to interpret the results may also be responsible for variations in clinical practice. In addition, opinions on how to correct ID and IDA differ, in relation to both clinical efficacy and safety. Conclusion The consequences of ID in patients with IBD are significant. Guidelines on diagnosis, treatment and follow-up of ID should be implemented. IDA is a manifestation of severe ID and preventive strategies focusing on efficient treatment of ID regardless of the level of haemoglobin should therefore be explored.

• Brun, Marthe Kirkesæther; Gehin, Johanna; Hammersbøen, Kristin Reine; Warren, David; Klaasen, Rolf & Sexton, Joseph [Vis alle 15 forfattere av denne artikkelen] (2024). Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials. The Lancet Rheumatology. 6(4), s. e226–e236. doi: 10.1016/S2665-9913(23)00341-7. Fulltekst i vitenarkiv
• Wolf, Asia-Sophia Fumika Michaela; Hammersbøen, Kristin Reine; Ørbo, Hilde Sofie Sager; Bhandari, Sabin; Solum, Guri & Kjønstad, Ingrid Fadum [Vis alle 30 forfattere av denne artikkelen] (2024). T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients on TNF inhibitor treatment: a prospective cohort study. EBioMedicine. 108. doi: 10.1016/j.ebiom.2024.105317. Fulltekst i vitenarkiv Vis sammendrag

  Background Understanding cellular responses to SARS-CoV-2 immunisations is important for informing vaccine recommendations in patients with inflammatory bowel disease (IBD) and other vulnerable patients on immunosuppressive therapies. This study investigated the magnitude and quality of T cell responses after multiple SARS-CoV-2 vaccine doses and COVID-19 breakthrough infection. Methods This prospective, observational study included patients with IBD and arthritis on tumour necrosis factor inhibitors (TNFi) receiving up to four SARS-CoV-2 vaccine doses. T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2–4 weeks after vaccinations and breakthrough infection to assess the frequency and polyfunctionality of responding cells, along with receptor-binding domain (anti-RBD) antibodies. Findings Between March 2, 2021, and December 20, 2022, 143 patients (118 IBD, 25 arthritis) and 73 healthy controls were included. In patients with either IBD or arthritis, humoral immunity was attenuated compared to healthy controls (median anti-RBD levels 3391 vs. 6280 BAU/ml, p = 0.008) after three SARS-CoV-2 vaccine doses. Patients with IBD had comparable quantities (median CD4 0.11% vs. 0.11%, p = 0.26, CD8 0.031% vs. 0.047%, p = 0.33) and quality (polyfunctionality score: 0.403 vs. 0.371, p = 0.39; 0.105 vs. 0.101, p = 0.87) of spike-specific T cells to healthy controls. Patients with arthritis had lower frequencies but comparable quality of responding T cells to controls. Breakthrough infection increased spike-specific CD8 T cell quality and T cell responses against non-spike peptides. Interpretation Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines.

• Alirezaylavasani, Amin; Egner, Ingrid Marie; Dahl, Tuva Børresdatter; Chopra, Adity; Kasahara, Taissa de Matos & Goll, Guro Løvik [Vis alle 15 forfattere av denne artikkelen] (2024). Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease. Clinical Immunology. ISSN 1521-6616. 271, s. 1–13. doi: 10.1016/j.clim.2024.110404. Fulltekst i vitenarkiv Vis sammendrag

  Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.

• Dotsenko, Valeriia; Tewes, Bernhard; Hils, Martin; Pasternack, Ralf; Isola, Jorma & Taavela, Juha [Vis alle 34 forfattere av denne artikkelen] (2024). Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease. Nature Immunology. ISSN 1529-2908. 25, s. 1218–1230. doi: 10.1038/s41590-024-01867-0. Fulltekst i vitenarkiv Vis sammendrag

  Transglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.

• Lindeman, Ida; Høydahl, Lene Støkken; Christophersen, Asbjørn Otto; Risnes, Louise Fremgaard; Jahnsen, Jørgen & Lundin, Knut [Vis alle 8 forfattere av denne artikkelen] (2024). Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease. Cell reports. 43:114045(4), s. 1–23. doi: 10.1016/j.celrep.2024.114045. Fulltekst i vitenarkiv Vis sammendrag

  Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls. They are clonally related to TG2-specific small intestinal plasma cells, and they express gut-homing molecules, indicating that they are plasma cell precursors. Unlike other IgA-switched cells, the TG2-specific cells are negative for CD27, placing them in the double-negative (IgD−CD27−) category. They have a plasmablast or activated memory B cell phenotype, and they harbor fewer variable region mutations than other IgA cells. Based on their similarity to naive B cells, we propose that autoreactive IgA cells in CeD are generated mainly through chronic recruitment of naive B cells via an extrafollicular response involving gluten-specific CD4+ T cells.

• Ørbo, Hilde Sofie Sager; Kasahara, Taissa de Matos; Wolf, Asia-Sophia Fumika Michaela; Bjørlykke, Kristin Hammersbøen; Sexton, Joseph & Jyssum, Ingrid [Vis alle 24 forfattere av denne artikkelen] (2024). Humoral and cellular responses to a fifth bivalent SARS-CoV-2 vaccine dose in patients with immune-mediated inflammatory diseases on tumour necrosis factor inhibitors: a prospective cohort study. The Lancet Regional Health - Europe. 48. doi: 10.1016/j.lanepe.2024.101121. Fulltekst i vitenarkiv Vis sammendrag

  Background As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibitors (TNFi). Methods In the longitudinal, observational Nor-vaC study, we assessed anti-spike and neutralising antibodies against Wuhan, Omicron BA.1 and BA.4, as well as frequency and polyfunctionality of responding T cells, following a fourth monovalent and a fifth bivalent (BA.1 or BA.4/5) vaccine dose in patients with or without hybrid immunity using TNFi. Findings Between December 17, 2021, and June 20, 2023, 456 infection-naïve patients with IMIDs using TNFi received a fourth vaccine dose and were otherwise eligible for inclusion. A total of 373/456 (82%) received a fifth vaccine dose, of these 190/373 (51%) had hybrid immunity defined as having had COVID-19 between the fourth and fifth dose. In patients with hybrid immunity, the fifth dose did not induce improved humoral responses compared to infection, neither with BA.1 (median anti-spike antibody concentrations 23,244 IU/ml (IQR 15,138–45,233) vs 36,341 IU/ml (11,887–53,710), p = 0.52) nor BA.4/5 (31,693 IU/ml (15,176–54,186), p = 0.30). Comparison of neutralising antibodies yielded similar results. In infection-naïve patients, a fifth BA.4/5 vaccine, but not the BA.1, induced slightly higher humoral responses (18,890 IU/ml (6494–50,211)) compared to the fourth dose (7304 IU/ml (3245–17,260), p < 0.0001). CD8 T cell responses remained stable following a fourth dose (median frequency of spike-specific cells 0.039% (IQR 0.010–0.14)), infection (0.058% (0.026–0.17)) and a fifth dose (0.058% (0.013–0.20). Interpretation In patients on TNFi with hybrid immunity, there was no immunological benefit of an updated fifth SARS-CoV-2 booster dose. Stable CD8 cellular responses following four doses indicate established protective immunity. Patients whose only risk factor is TNFi may in future follow vaccine recommendations for the general population.

• Espeland, Kristian; Christensen, Eidi; Aandahl, Astrid; Ulvær, Andreas; Warloe, Trond & Kleinauskas, Andrius [Vis alle 11 forfattere av denne artikkelen] (2024). Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn’s Disease—A First-in-Human Phase I/II Study. Journal of Clinical Medicine. 13:6198(20), s. 1–12. doi: 10.3390/jcm13206198. Fulltekst i vitenarkiv Vis sammendrag

  Background/Objectives: With the increasing prevalence of Crohn’s disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies.

• Das, Saykat; Stamnæs, Jorunn; Høydahl, Lene Støkken; Skagen, Christine; Lundin, Knut & Jahnsen, Jørgen [Vis alle 8 forfattere av denne artikkelen] (2024). Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease. Journal of Autoimmunity. ISSN 0896-8411. 146, s. 1–10. doi: 10.1016/j.jaut.2024.103241. Fulltekst i vitenarkiv Vis sammendrag

  Many antibody responses induced by infection, vaccination or autoimmunity show signs of convergence across individuals with epitope-dependent selection of particular variable region gene segments and complementarity determining region 3 properties. However, not much is known about the relationship between antigen-specific effector cells and antigen-specific precursors present in the naïve B-cell repertoire. Here, we sought to address this relationship in the context of celiac disease, where there is a stereotyped autoantibody response against the enzyme transglutaminase 2 (TG2). By generating TG2-specific monoclonal antibodies from both duodenal plasma cells and circulating naïve B cells, we demonstrate a discord between the naïve TG2-specific repertoire and the cells that are selected for autoantibody production. Hence, the naïve repertoire does not fully reflect the epitope preference and gene usage observed for memory B cells and plasma cells. Instead, distinct naïve B cells that target particular TG2 epitopes appear to be selectively activated at the expense of TG2-binding B cells targeting other epitopes.

• Peyrin‐Biroulet, Laurent; Arkkila, Perttu; Armuzzi, Alessandro; Danese, Silvio; Ferrante, Marc & Guardiola, Jordi [Vis alle 17 forfattere av denne artikkelen] (2024). Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn’s disease and ulcerative colitis included in randomised controlled trials. BMC Gastroenterology. 24(1). doi: 10.1186/s12876-024-03163-5. Fulltekst i vitenarkiv Vis sammendrag

  Background While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn’s disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. Aim Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. Methods Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. Results We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. Conclusion IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.

• Ørbo, Hilde Sofie Sager; Hammersbøen, Kristin Reine; Sexton, Joseph; Jyssum, Ingrid; Tveter, Anne Therese & Christensen, Ingrid Egeland [Vis alle 18 forfattere av denne artikkelen] (2024). Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study. RMD Open. 10(2). doi: 10.1136/rmdopen-2023-003545. Fulltekst i vitenarkiv Vis sammendrag

  Objectives To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. Methods IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2–5 weeks post-immunisation. Results Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)). Conclusion Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals. Trial registration number NCT04798625.

• Brun, Marthe Kirkesæther; Hammersbøen, Kristin Reine; Viken, Marte Kathrine; Stenvik, Grethe-Elisabeth; Klaasen, Rolf & Gehin, Johanna [Vis alle 18 forfattere av denne artikkelen] (2023). HLA-DQ2 is associated with anti-drug antibody formation to infliximab in patients with immune-mediated inflammatory diseases. Journal of Internal Medicine. ISSN 0954-6820. 293(5), s. 648–655. doi: 10.1111/joim.13616. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Immunogenicity to tumour necrosis factor inhibitors is a significant clinical problem leading to treatment failure and adverse events. The study aimed to assess human leukocyte antigen (HLA) associations with anti‐drug antibody (ADAb) formation to infliximab. Methods Immune‐mediated inflammatory disease patients on infliximab therapy ( n  = 612) were included. Neutralising ADAb were assessed with a drug‐sensitive assay. Next generation sequencing‐based HLA typing was performed. Results Overall, 147 (24%) patients developed ADAb. Conditional analyses indicated HLA‐DQB1 ( p  = 1.4 × 10 −6 ) as a primary risk locus. Highest risk of ADAb was seen when carrying at least one of the HLA‐DQ2 haplotypes; DQB1*02:01–DQA1*05:01 or DQB1*02:02–DQA1*02:01 (OR 3.18, 95% CI 2.15–4.69 and p  = 5.9 × 10 −9 ). Results were consistent across diseases and when adjusting for concomitant immunomodulator. Computational predictions indicated that these HLA‐DQ2 haplotypes bind to peptide motifs from infliximab light chain. Conclusion A genome‐wide significant association between two HLA‐DQ2 haplotypes and the risk of ADAb formation to infliximab was identified, suggesting that HLA‐DQ2 testing may facilitate personalised treatment decisions.

• Chlubnova, Marketa; Christophersen, Asbjørn Otto; Sandve, Geir Kjetil Ferkingstad; Lundin, Knut Erik Aslaksen; Jahnsen, Jørgen & Dahal-Koirala, Shiva [Vis alle 7 forfattere av denne artikkelen] (2023). Identification of gluten T cell epitopes driving celiac disease. Science Advances. 9(4), s. 1–8. doi: 10.1126/sciadv.ade5800. Fulltekst i vitenarkiv Vis sammendrag

  CD4+ T cells specific for cereal gluten proteins are key players in celiac disease (CeD) pathogenesis. While several CeD-relevant gluten T cell epitopes have been identified, epitopes recognized by a substantial proportion of gluten-reactive T cells remain unknown. The identification of such CeD-driving gluten epitopes is important for the food industry and in clinical settings. Here, we have combined the knowledge of a distinct phenotype of gluten-reactive T cells and key features of known gluten epitopes for the discovery of unknown epitopes. We tested 42 wheat gluten–reactive T cell clones, isolated on the basis of their distinct phenotype and with no reactivity to known epitopes, against a panel of synthetic peptides bioinformatically identified from a wheat gluten protein database. We were able to assign reactivity to 10 T cell clones and identified a 9-nucleotide oligomer core region of five previously uncharacterized gliadin/glutenin epitopes. This work represents an advance in the effort to identify CeD-driving gluten epitopes.

• Espeland, Kristian; Kleinauskas, Andrius; Juzenas, Petras; Darvekar, Sagar Ramesh; Vasovic, Vlada & Warloe, Trond [Vis alle 9 forfattere av denne artikkelen] (2023). Photodynamic effects with 5-aminolevulinic acid on cytokines and exosomes in human peripheral blood mononuclear cells from patients with Crohn’s disease. International Journal of Molecular Sciences. ISSN 1661-6596. 24(5), s. 1–20. doi: 10.3390/ijms24054554. Fulltekst i vitenarkiv Vis sammendrag

  Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) which is the precursor of the photosensitizer protoporphyrin IX (PpIX) is an available treatment for several diseases. ALA-PDT induces the apoptosis and necrosis of target lesions. We have recently reported the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). This study has investigated the ALA-PDT-mediated effects on PBMC subsets from patients with active Crohn’s disease (CD). No effects on lymphocyte survival after ALA-PDT were observed, although the survival of CD3−/CD19+ B-cells seemed slightly reduced in some samples. Interestingly, ALA-PDT clearly killed monocytes. The subcellular levels of cytokines and exosomes associated with inflammation were widely downregulated, which is consistent with our previous findings in PBMCs from healthy human subjects. These results suggest that ALA-PDT may be a potential treatment candidate for CD and other immune-mediated diseases.

• Das, Saykat; Stamnæs, Jorunn; Kemppainen, Esko; Hervonen, Kaisa; Lundin, Knut & Parmar, Naveen [Vis alle 12 forfattere av denne artikkelen] (2023). Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis. Advanced Science. 10:2300401(25), s. 1–10. doi: 10.1002/advs.202300401. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto‐antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto‐antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto‐antibodies are specific for either TG2 or TG3 with no TG2–TG3 cross reactivity. By generating monoclonal antibodies from TG3‐specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2‐specific and TG3‐specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase‐reactive populations show distinct selection of certain heavy and light chain V‐genes. Mass spectrometry analysis of TG3‐specific serum IgA corroborates preferential usage of IGHV2‐5 in combination with IGKV4‐1 . Collectively, these results demonstrate parallel induction of anti‐TG2 and anti‐TG3 auto‐antibody responses involving separate B‐cell populations in DH patients.

• Jørgensen, Kristin Kaasen; Høivik, Marte Lie; Chopra, Adity; Benth, Jurate Saltyte; Ricanek, Petr & Moum, Bjørn Allan [Vis alle 18 forfattere av denne artikkelen] (2023). Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(8), s. 874–882. doi: 10.1080/00365521.2023.2177884. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. Materials and methods This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. Results In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. Conclusions Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

• Kalla, Rahul; Adams, Alex T; Nowak, Jan K; Bergemalm, Daniel; Vatn, Simen Svendsen & Ventham, Nicholas T [Vis alle 20 forfattere av denne artikkelen] (2023). Analysis of Systemic Epigenetic Alterations in Inflammatory Bowel Disease: Defining Geographical, Genetic and Immune-Inflammatory influences on the Circulating Methylome. Journal of Crohn's and Colitis. ISSN 1873-9946. 17(2), s. 170–184. doi: 10.1093/ecco-jcc/jjac127. Fulltekst i vitenarkiv
• Chauhan, Sudhir Kumar; Casado, Raquel Bartolome; Landsverk, Ole J. B.; Johannessen, Hanna; Phung, Danh Thanh & Nilsen, Hogne Røed [Vis alle 14 forfattere av denne artikkelen] (2023). Human small intestine contains 2 functionally distinct regulatory T-cell subsets. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. 152(1), s. 278–289.e6. doi: 10.1016/j.jaci.2023.02.030. Fulltekst i vitenarkiv Vis sammendrag

  Background Regulatory T (Treg) CD4 cells in mouse gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Treg cells in the human gut is limited. Objective We performed a detailed characterization of Foxp3+ CD4 Treg cells in human normal small intestine (SI) as well as from transplanted duodenum and celiac disease lesions. Methods Treg cells and conventional CD4 T cells derived from SI were subjected to extensive immunophenotyping and their suppressive activity and ability to produce cytokines assessed. Results SI Foxp3+ CD4 T cells were CD45RA−CD127−CTLA-4+ and suppressed proliferation of autologous T cells. Approximately 60% of Treg cells expressed the transcription factor Helios. When stimulated, Helios-negative Treg cells produced IL-17, IFN-γ, and IL-10, whereas Helios-positive Treg cells produced very low levels of these cytokines. By sampling mucosal tissue from transplanted human duodenum, we demonstrated that donor Helios-negative Treg cells persisted for at least 1 year after transplantation. In normal SI, Foxp3+ Treg cells constituted only 2% of all CD4 T cells, while in active celiac disease, both Helios-negative and Helios-positive subsets expanded 5- to 10-fold. Conclusion The SI contains 2 subsets of Treg cells with different phenotypes and functional capacities. Both subsets are scarce in healthy gut but increase dramatically in active celiac disease.

• Bjørlykke, Kristin H.; Ørbo, Hilde Sofie Sager; Tveter, Anne Therese; Jyssum, Ingrid; Sexton, Joseph & Tran, Trung [Vis alle 21 forfattere av denne artikkelen] (2022). Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. The Lancet Rheumatology. 5(1), s. e36–e46. doi: 10.1016/S2665-9913(22)00330-7. Fulltekst i vitenarkiv Vis sammendrag

  Background Data on response and safety of repeated vaccinations and hybrid immunity in patients with immune-mediated inflammatory diseases on immunosuppressive therapy is needed to further develop vaccination strategies in this vulnerable population. This study aimed to evaluate hybrid immunity and humoral immune response and safety of four SARS-CoV-2 vaccine doses in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. Methods This prospective observational Norwegian study of vaccine response to COVID-19 (Nor-vaC) included adult patients aged 18 years and older with immune-mediated inflammatory diseases (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis) on immunosuppressive therapy, who had received four SARS-CoV-2 vaccine doses (vaccine group) or three vaccine doses followed by COVID-19 (hybrid group), and healthy controls receiving three vaccine doses (control group). Patients were recruited from the Division of Rheumatology at Diakonhjemmet Hospital, Oslo, and the Department of Gastroenterology at Akershus University Hospital, Lørenskog. Patients who had COVID-19 before the third vaccine dose, and patients with allergies or intolerances to elements of the vaccine were excluded. Antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD antibodies) were assessed 2–4 weeks following vaccination or COVID-19. This study is registered at Clinialtrials.gov, NCT04798625. Findings Between Nov 12, 2021, and April 19, 2022, 1458 participants with immune-mediated inflammatory diseases provided post-vaccination samples at 2–4 weeks following a third vaccine dose. After 544 participants were excluded, 715 (78%) of the remaining 914 participants received the fourth dose of the vaccine, and of these, 536 (75%) provided post-vaccination samples 2–4 weeks after their fourth vaccination (vaccine group). 199 (22%) of the 914 had COVID-19 after their third dose of the vaccine and of these, 167 (84%) provided samples (hybrid group). 256 of the eligible 703 patients had rheumatoid arthritis, 107 had spondyloarthritis, 115 had psoriatic arthritis, 130 had Crohn's disease, and 95 had ulcerative colitis). Median age was 56 years [IQR 45–65], 398 (57%) were women, and 305 (43%) were men. Patients in the vaccine group had higher anti-RBD antibody concentrations following the fourth vaccine dose (median 6192 BAU/ml [IQR 2878–11 243]) than after the third dose (median 5087 BAU/ml [1250–9081]; p< 0·0001), but lower antibody concentrations than the control group following the third dose (median 7595 BAU/ml [5916–12 001]; p< 0·0001). Antibody concentrations were higher in the patients in the hybrid group (23 548 BAU/ml [IQR 11 440–35 935]) than in the vaccine group (p<0·0001). No difference was found in antibody concentrations between the fourth dose of BNT162b2 (full-dose) and mRNA-1273 (half-dose). Patients and controls had a comparable safety profile after both three and four vaccine doses. Interpretation Vaccine boosters improve humoral immune responses and are safe in patients with immune-mediated inflammatory diseases on immunosuppressive therapy, and administration should be considered regularly in this patient group. Hybrid immunity with omicron induces a strong humoral response suggesting longer intervals between booster doses in this patient group.

• Peyrin-Biroulet, Laurent; Arkkila, Perttu; Armuzzi, Alessandro; Danese, Silvio; Guardiola, Jordi & Jahnsen, Jørgen [Vis alle 16 forfattere av denne artikkelen] (2022). Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: a systematic review and meta-analysis. BMC Gastroenterology. 22(1). doi: 10.1186/s12876-022-02347-1. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. Methods We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn’s disease or ulcerative colitis. Results We identified six eligible Crohn’s disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn’s disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn’s disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn’s disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn’s disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. Conclusions Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn’s disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.

• Brun, Marthe Kirkesæther; Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Sexton, Joseph; Gehin, Johanna Elin & Sandanger, Øystein [Vis alle 15 forfattere av denne artikkelen] (2022). Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial. Journal of Internal Medicine. ISSN 0954-6820. 292(3), s. 477–491. doi: 10.1111/joim.13495. Fulltekst i vitenarkiv Vis sammendrag

  Background Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events. Objective To identify risk factors for ADAb in the early phase of infliximab treatment. Methods Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders. Results ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0–3.6]) and lifetime smoking (OR, 2.0 [CI 1.1–3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2–0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2–0.8]) reduced the risk of ADAb. Higher disease activity during follow-up (OR, 1.1 [CI 1.0–1.1]) and “drug holidays” of more than 11 weeks (OR, 4.1 [CI 1.2–13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0–0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6–0.8]) reduced the risk of immunogenicity. Conclusion Several risk factors for ADAb formation during early-phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.

• Christophersen, Asbjørn Otto; Dahal-Koirala, Shiva; Chlubnova, Marketa; Jahnsen, Jørgen; Lundin, Knut & Sollid, Ludvig Magne (2022). Phenotype-Based Isolation of Antigen-Specific CD4+ T Cells in Autoimmunity: A Study of Celiac Disease. Advanced Science. 9(10), s. 1–10. doi: 10.1002/advs.202104766. Fulltekst i vitenarkiv Vis sammendrag

  The pathogenic immune response in celiac disease (CeD) is orchestrated by phenotypically distinct CD4+ T cells that recognize gluten epitopes in the context of disease-associated HLA-DQ allotypes. Cells with the same distinct phenotype, but with elusive specificities, are increased across multiple autoimmune conditions. Here, whether sorting of T cells based on their distinct phenotype (Tphe cells) yields gluten-reactive cells in CeD is tested. The method′s efficiency is benchmarked by parallel isolation of gluten-reactive T cells (Ttet cells), using HLA-DQ:gluten peptide tetramers. From gut biopsies of 12 untreated HLA-DQ2.5+ CeD patients, Ttet+/Tphe+, Ttet−/Tphe+, and Ttet−/Tphe− cells are sorted for single-cell T-cell receptor (TCR)-sequencing (n = 8) and T-cell clone (TCC)-generation (n = 5). The generated TCCs are TCR sequenced and tested for their reactivity against deamidated gluten. Gluten-reactivity is observed in 91.2% of Ttet+/Tphe+ TCCs, 65.3% of Ttet−/Tphe+ TCCs and 0% of Ttet−/Tphe− TCCs. TCR sequencing reveals clonal expansion and sequence sharing across patients, features reflecting antigen-driven responses. The feasibility to isolate antigen-specific CD4+ T cells by the sole use of phenotypic markers in CeD outlines a potential avenue for characterizing disease-driving CD4+ T cells in autoimmune conditions.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Tran, Trung; Sexton, Joseph & Provan, Sella Aarrestad [Vis alle 22 forfattere av denne artikkelen] (2022). Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy. Arthritis & Rheumatology. ISSN 2326-5191. 74(8), s. 1321–1332. doi: 10.1002/art.42153. Fulltekst i vitenarkiv Vis sammendrag

  Objective Immunogenicity and safety following receipt of the standard SARS–CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS–CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. Methods Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS–CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS–CoV-2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS–Cov-2 spike protein, were allotted a third vaccine dose. Results A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. Conclusion IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

• Atlasy, Nader; Bujko, Anna; Bækkevold, Espen Sønderaal; Brazda, Peter; Janssen-Megens, Eva & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2022). Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease. Nature Communications. 13:4920(1), s. 1–14. doi: 10.1038/s41467-022-32691-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Celiac disease is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine leading to destruction of the lining epithelium. Current treatment focusses on lifelong adherence to a gluten-free diet. Gluten-specific CD4 + T cells and cytotoxic intraepithelial CD8 + T cells have been proposed to be central in disease pathogenesis. Here we use unbiased single-cell RNA-sequencing and explore the heterogeneity of CD45 + immune cells in the human small intestine. We show altered myeloid cell transcriptomes present in active celiac lesions. CD4 + and CD8 + T cells transcriptomes show extensive changes and we define a natural intraepithelial lymphocyte population that is reduced in celiac disease. We show that the immune landscape in Celiac patients on a gluten-free diet is only partially restored compared to control samples. Altogether, we provide a single cell transcriptomic resource that can inform the immune landscape of the small intestine during Celiac disease.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Christensen, Ingrid Egeland & Tran, Trung [Vis alle 20 forfattere av denne artikkelen] (2022). Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. RMD Open. 8(2). doi: 10.1136/rmdopen-2022-002417. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. Methods Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2–4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2–4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. Results 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138–8732) compared with 4495 (1591–6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150–4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p<0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. Conclusions This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. Trial registration number NCT04798625.

• Vatn, Simen Svendsen; Lindstrøm, Jonas Christoffer; Moen, Aina Elisabeth Fossum; Brackmann, Stephan Andreas; Tannæs, Tone Møller & Olbjørn, Christine [Vis alle 19 forfattere av denne artikkelen] (2022). Mucosal Gene Transcript Signatures in Treatment Naïve Inflammatory Bowel Disease: A Comparative Analysis of Disease to Symptomatic and Healthy Controls in the European IBD-Character Cohort. Clinical and Experimental Gastroenterology. 15, s. 5–25. doi: 10.2147/CEG.S343468. Fulltekst i vitenarkiv Vis sammendrag

  Background: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naïve patients and compared them to both symptomatic and healthy controls. Methods: Altogether, 323 subjects were included: Crohn’s disease (N = 75), ulcerative colitis (N = 87) and IBD unclassified (N = 3). Additionally, there were two control groups: symptomatic controls (N = 131) and healthy controls (N = 27). Mucosal biopsies were collected during ileocolonoscopy and gene expression in inflamed and non-inflamed mucosa was explored. Gene expression profiling was performed using Agilent G3 Human Gene Expression 860K v3 One-Color microarray. We recorded information about treatment escalation to anti-TNF agents or surgery, and anti-TNF response, to explore predictive opportunities of the mucosal transcriptome. Results: Gene expression profiles in symptomatic controls in whom IBD had been excluded resembled that of IBD patients and diverged from that of healthy controls. In non-inflamed Crohn’s disease and ulcerative colitis, gene set enrichment analysis revealed dysregulation of pathways involved in basic cellular biological processes. Mitochondria-associated pathways were dysregulated both in non-inflamed and inflamed Crohn’s disease and ulcerative colitis (> 2.6 normalized enrichment scores <− 1.8). Gene expression signatures of Crohn’s disease and ulcerative colitis did not predict time for treatment escalation (p = 0.175). No significant association was found between gene expression signatures and anti-TNF response. Conclusion: Non-inflamed samples are probably superior to inflamed samples when exploring gene expression signatures in IBD and might reveal underlying mechanisms central for disease initiation. The gene expression signatures of the control groups were related to if they were symptomatic or not, which may have important implications for future study designs.

• Espeland, Kristian; Kleinauskas, Andrius; Juzenas, Petras; Brech, Andreas; Darvekar, Sagar & Vasovic, Vlada [Vis alle 10 forfattere av denne artikkelen] (2022). Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells. Biomedicines. 10(2). doi: 10.3390/biomedicines10020232. Fulltekst i vitenarkiv Vis sammendrag

  Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment. We report from the first study on the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). The treatment reduced the cytokines and exosomes studied, although there was variation among individual PBMC samples. This reduction is consistent with PDT-mediated survivals of subsets of PBMCs. More specifically, the ALA-PDT treatment apparently decreased all pro-inflammatory cytokines included, suggesting that this treatment may provide a strong anti-inflammatory effect. In addition, the treatment has decreased the levels of different types of exosomes, the HLA-DRDPDQ exosome in particular, which plays an important role in the rejection of organ transplantation as well as autoimmune diseases. These results may suggest future therapeutic strategies of ALA-PDT.

• Nowak, Jan K.; Adams, Alex T.; Kalla, Rahul; Lindstrøm, Jonas Christoffer; Vatn, Simen Svendsen & Bergemalm, Daniel [Vis alle 15 forfattere av denne artikkelen] (2022). Characterisation of the Circulating Transcriptomic Landscape in Inflammatory Bowel Disease Provides Evidence for Dysregulation of Multiple Transcription Factors Including NFE2, SPI1, CEBPB, and IRF2. Journal of Crohn's and Colitis. ISSN 1873-9946. 16(8), s. 1255–1268. doi: 10.1093/ecco-jcc/jjac033. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Aim To assess the pathobiological and translational importance of whole-blood transcriptomic analysis in inflammatory bowel disease [IBD]. Methods We analysed whole-blood expression profiles from paired-end sequencing in a discovery cohort of 590 Europeans recruited across six countries in the IBD Character initiative (newly diagnosed patients with Crohn’s disease [CD; n = 156], ulcerative colitis [UC; n = 167], and controls [n = 267]), exploring differential expression [DESeq2], co-expression networks [WGCNA], and transcription factor involvement [EPEE, ChEA, DoRothEA]. Findings were validated by analysis of an independent replication cohort [99 CD, 100 UC, 95 controls]. In the discovery cohort, we also defined baseline expression correlates of future treatment escalation using cross-validated elastic-net and random forest modelling, along with a pragmatic ratio detection procedure. Results Disease-specific transcriptomes were defined in IBD [8697 transcripts], CD [7152], and UC [8521], with the most highly significant changes in single genes, including CD177 (log2-fold change [LFC] = 4.63, p = 4.05 × 10-118), MCEMP1 [LFC = 2.45, p = 7.37 × 10-109], and S100A12 [LFC = 2.31, p = 2.15 × 10-93]. Significantly over-represented pathways included IL-1 [p = 1.58 × 10-11], IL-4, and IL-13 [p = 8.96 × 10-9]. Highly concordant results were obtained using multiple regulatory activity inference tools applied to the discovery and replication cohorts. These analyses demonstrated central roles in IBD for the transcription factors NFE2, SPI1 [PU.1], CEBPB, and IRF2, all regulators of cytokine signalling, based on a consistent signal across cohorts and transcription factor ranking methods. A number of simple transcriptome-based models were associated with the need for treatment escalation, including the binary CLEC5A/CDH2 expression ratio in UC (hazard ratio = 23.4, 95% confidence interval [CI] 5.3–102.0). Conclusions Transcriptomic analysis has allowed for a detailed characterisation of IBD pathobiology, with important potential translational implications.

• Hammersbøen, Kristin Reine; Jahnsen, Jørgen; Brynskov, Jørn; Molander, Pauliina; Eberhardson, Michael & Davidsdottir, Loà G. [Vis alle 13 forfattere av denne artikkelen] (2022). Therapeutic drug monitoring in inflammatory bowel disease: implementation, utilization, and barriers in clinical practice in Scandinavia. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. doi: 10.1080/00365521.2022.2108684. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01–0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.

• Christensen, Ingrid Egeland; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Tran, Trung & Mjaaland, Siri [Vis alle 19 forfattere av denne artikkelen] (2022). The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study. BMC Medicine. 20(1), s. 1–13. doi: 10.1186/s12916-022-02587-8. Fulltekst i vitenarkiv Vis sammendrag

  Background The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. Methods IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6–48 days, second within 49–123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. Results A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn’s disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15–24] and 97 days [87–105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018–6068] in patients and 6187 BAU/ml [4105–7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58–1053] in patients and 1520 BAU/ml [979–3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was − 83% in patients and − 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls − 4.9 (95% CI − 7.4 to − 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. Conclusions Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

• Zhou, Chunyan; Østerbye, Thomas; Bach, Emil; Dahal-Koirala, Shiva; Høydahl, Lene Støkken & Steinsbø, Øyvind [Vis alle 11 forfattere av denne artikkelen] (2022). Focused B cell response to recurring gluten motif with implications for epitope spreading in celiac disease. Cell reports. 41:111541(4), s. 1–16. doi: 10.1016/j.celrep.2022.111541. Fulltekst i vitenarkiv Vis sammendrag

  Antibodies to deamidated gluten peptides are accurate diagnostic markers of celiac disease. However, binding of patient antibodies to all possible gluten epitopes has not previously been investigated. Here, we assess serum antibody specificity across the gluten proteome by use of high-density peptide arrays. We confirm the importance of deamidation for antibody binding, and we show that the response is remarkably focused on the known epitope QPEQPFP (where E results from deamidation of Q). In addition, we describe an epitope in native (non-deamidated) gluten, QQPEQII (where E is gene encoded), which is associated with both B cell and T cell reactivity. Antibodies to this native epitope are cross-reactive with the major deamidated epitope due to recognition of the shared PEQ motif. Since cross-reactive B cells can present peptides to different gluten-specific T cells, we propose that such B cells play a role in epitope spreading by engaging T cells with multiple specificities.

• Jelsness-Jørgensen, Lars-Petter; Moum, Bjørn Allan; Grimstad, Tore Bjørn; Jahnsen, Jørgen; Hovde, Øistein & Frigstad, Svein Oskar [Vis alle 7 forfattere av denne artikkelen] (2022). The multidimensional fatigue inventory (MFI-20): psychometrical testing in a Norwegian sample of inflammatory bowel disease (IBD) patients. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. s. 1–7. doi: 10.1080/00365521.2022.2029939. Fulltekst i vitenarkiv Vis sammendrag

  OBJECTIVES To evaluate the psychometric properties of the Norwegian version of the multidimensional fatigue inventory (MFI-20) in patients with inflammatory bowel disease. METHODS Participants were recruited from nine hospitals in the southeastern and western parts of Norway. Clinical and sociodemographic data were collected, and participants completed the MFI-20, as well as the Fatigue Questionnaire (FQ). In addition to a confirmatory factor analysis, validity, reliability, test-retest and responsiveness were evaluated. RESULTS In total, 410 patients were included. The Norwegian MFI-20 had an acceptable model fit when compared to the original five-dimensional structure. A positive correlation was observed between the dimensions of MFI-20 and the FQ. MFI-20 scores increased according to subjective disease activity, but no differences were observed when using a calprotectin cut-off < or > =250 µg/g mg/kg. All MFI-20 dimensions except ‘reduced motivation’ in both ulcerative colitis (UC) and Crohn’s disease (CD) patients had alpha Cronbach alpha values ≥70, and test-retest reliability revealed good to excellent values. Merely one dimension (Reduced activity) in UC patients reporting improvement did not reach the threshold for acceptable responsiveness according to Guyatt statistics. CONCLUSIONS The Norwegian version of MFI-20 is valid, reliable and responsive. The instrument can safely be used in studies using fatigue as an endpoint.

• Jyssum, Ingrid; Kared, Hassen; Tran, Trung; Tveter, Anne Therese; Provan, Sella Aarrestad & Sexton, Joseph [Vis alle 22 forfattere av denne artikkelen] (2021). Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study. The Lancet Rheumatology. 00. doi: 10.1016/S2665-9913(21)00394-5. Fulltekst i vitenarkiv Vis sammendrag

  Background In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. Methods This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2–4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7–10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. Findings Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222–324] in responders vs 107 days [80–152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. Interpretation This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6–9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response.

• Syversen, Silje Watterdal; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Brun, Marthe Kirkesæther; Sandanger, Øystein & Hammersbøen, Kristin Reine [Vis alle 33 forfattere av denne artikkelen] (2021). Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 326(23), s. 2375–2384. doi: 10.1001/jama.2021.21316. Fulltekst i vitenarkiv Vis sammendrag

  IMPORTANCE Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. OBJECTIVE To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. DESIGN, SETTING, AND PARTICIPANTS Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. INTERVENTIONS Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). MAIN OUTCOME AND MEASURES The primary outcomewas sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. RESULTS Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6%(95%CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively. CONCLUSIONS AND RELEVANCE Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDMwas more effective than treatment without TDM in sustaining disease control without diseaseworsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03074656

• Bergemalm, Daniel; Andersson, Erik; Hultdin, Johan; Eriksson, Carl; Rush, Stephen T. & Kalla, Rahul [Vis alle 20 forfattere av denne artikkelen] (2021). Systemic Inflammation in Preclinical Ulcerative Colitis. Gastroenterology. ISSN 0016-5085. 161(5), s. 1526–1539.e9. doi: 10.1053/j.gastro.2021.07.026. Fulltekst i vitenarkiv
• Syversen, Silje Watterdal; Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Sandanger, Øystein; Sexton, Joseph & Olsen, Inge Christoffer [Vis alle 33 forfattere av denne artikkelen] (2021). Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 325(17), s. 1744–1754. doi: 10.1001/jama.2021.4172. Fulltekst i vitenarkiv Vis sammendrag

  Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear. Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. Design, setting, and participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019. Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204). Main outcomes and measures: The primary end point was clinical remission at week 30. Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively. Conclusions and relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates.

• Christophersen, Asbjørn Otto; Zühlke, Stephanie; Lund, Eivind Gard; Snir, Omri; Dahal-Koirala, Shiva & Risnes, Louise Fremgaard [Vis alle 9 forfattere av denne artikkelen] (2021). Pathogenic T cells in celiac disease change phenotype on gluten challenge: Implications for T-cell-directed therapies. Advanced Science. 8(21), s. 1–11. doi: 10.1002/advs.202102778. Fulltekst i vitenarkiv
• Lindeman, Ida; Zhou, Chunyan; Eggesbø, Linn Margrethe; Miao, Zhichao; Polak, Justyna & Lundin, Knut Erik Aslaksen [Vis alle 10 forfattere av denne artikkelen] (2021). Longevity, clonal relationship, and transcriptional program of celiac disease-specific plasma cells. Journal of Experimental Medicine (JEM). ISSN 0022-1007. 218:e20200852(2), s. 1–16. doi: 10.1084/jem.20200852. Fulltekst i vitenarkiv Vis sammendrag

  Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGPs) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls and performed RNA sequencing with clonal inference and transcriptomic analysis of 3,251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific and non–disease-specific PCs and between short-lived and long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term–treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.

• Reinisch, Walter; Gecse, Krisztina; Halfvarson, Jonas; Irving, Peter M.; Jahnsen, Jørgen & Peyrin-Biroulet, Laurent [Vis alle 9 forfattere av denne artikkelen] (2021). Clinical Practice of Adalimumab and Infliximab Biosimilar Treatment in Adult Patients With Crohn's Disease. Inflammatory Bowel Diseases. ISSN 1078-0998. 27(1), s. 106–122. doi: 10.1093/ibd/izaa078. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The introduction of tumor necrosis factor (TNF) inhibitors has significantly changed the treatment landscape in Crohn’s disease (CD). The overall therapeutic achievements with TNF inhibitors such as infliximab, adalimumab, and certolizumab pegol paved the way to push the boundaries of treatment goals beyond symptomatic relief and toward cessation of objective signs of inflammation, including endoscopic remission. Even though these agents are widely used for the treatment of moderate to severe CD, heterogeneity still exists in translating evidence-based guidelines on the use of anti-TNF agents into actual treatment algorithms in CD. This might be due to several reasons including disparities in health expenditure policies; lack of harmonization between countries; and variations in assessment of disease severity, use of disease monitoring tools, or application of treatment targets by physicians. With the advent of biosimilars, patent-free versions of reference biologics are now available to minimize health inequalities in drug availability. In this context, this article aims to provide practical clinical guidance for the use of infliximab and adalimumab biosimilars in patients with moderate to severe CD by outlining different clinical scenarios that patients may encounter during their treatment journey.

• Detlie, Trond Espen; Jahnsen, Marte Eide; Jahnsen, Jørgen; Lindstrøm, Jonas Christoffer; Moum, Bjørn & Finnes, Elisabeth [Vis alle 7 forfattere av denne artikkelen] (2021). Hypophosphatemia after high-dose intravenous iron treatment in patients with inflammatory bowel disease: Mechanisms and possible clinical impact. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 27(17), s. 2039–2053. doi: 10.3748/wjg.v27.i17.2039. Fulltekst i vitenarkiv
• Schuppan, Detlef; Maki, Markku; Lundin, Knut Erik Aslaksen; Isola, Jorma; Friesing-Sosnik, Tina & Taavela, Juha [Vis alle 26 forfattere av denne artikkelen] (2021). A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease. New England Journal of Medicine. ISSN 0028-4793. 385(1), s. 35–45. doi: 10.1056/NEJMoa2032441. Fulltekst i vitenarkiv Vis sammendrag

  Background: In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease. Methods: In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life). Results: Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P = 0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group. Conclusions: In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. (Funded by Dr. Falk Pharma; CEC-3 EudraCT number, 2017-002241-30.). Copyright © 2021 Massachusetts Medical Society.

• Romstad, Katrine Maria Kauczynska; Detlie, Trond Espen; Søberg, Taran; Thomas, Owen Matthew Truscott; Ricanek, Petr & Jahnsen, Marte Eide [Vis alle 8 forfattere av denne artikkelen] (2021). Treatment and outcome of gastrointestinal bleeding due to peptic ulcers and erosions–(BLUE study). Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 57(1), s. 8–15. doi: 10.1080/00365521.2021.1988701. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Peptic ulcers and erosions are the most common causes of upper gastrointestinal bleeding. The aim of this study was to investigate the management and outcomes of these patients. Materials and methods A total of 543 patients with endoscopically confirmed bleeding from peptic ulcers and erosions were included from March 2015 to December 2017. The patient characteristics, endoscopic findings, Forrest classification and endoscopic treatment were recorded. Moreover, the rebleeding rates, repeated endoscopies and transcatheter angiographic embolization and surgery incidences were registered. A follow-up endoscopy after discharge from the hospital was scheduled. Results Among the patients, high-risk stigmata ulcers were present in 36% (198/543) and low-risk stigmata ulcers and erosions in 60% (327/543) at first endoscopy. Endoscopic therapy was performed in 30% (165/543) of the patients, and hemostasis was achieved in 94% (155/165). The incidence of rebleeding was 9% (49/543) for the whole cohort and 14.8% (23/155) for those patients who had received successful endoscopic treatment. Moreover, rebleeding was significantly more frequent in duodenal ulcers than in gastric ulcers (11.9% vs 4.0%, p = .004). In a multivariable analysis, rebleeding was significantly related to comorbidity and Forrest classification. Transcatheter angiographic embolization and surgery were required in 6% (34/543) and 0.07% (4/543) of patients, respectively. Complete peptic ulcer healing was found at follow-up in 73.3% (270/368) of patients. Conclusions Endoscopic hemostasis was achieved in the majority of patients with high-risk ulceration, although the occurrence of rebleeding is a significant challenge, especially in patients with duodenal ulcers. Clinical trial registration: Bleeding Ulcer and Erosions Study (BLUE Study), ClinicalTrials.gov identifier: NCT03367897.

• Monstad, Iril Lovise; Solberg, Inger Camilla; Småstuen, Milada Cvancarova; Hovde, Oistein; Henriksen, Magne & Huppertz-Hauss, Gert [Vis alle 12 forfattere av denne artikkelen] (2021). Outcome of Ulcerative Colitis 20 Years after Diagnosis in a Prospective Population-based Inception Cohort from South-Eastern Norway, the IBSEN Study. Journal of Crohn's and Colitis. ISSN 1873-9946. 15(6), s. 969–979. doi: 10.1093/ecco-jcc/jjaa232. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims: The long-term course of ulcerative colitis [UC] is difficult to predict. Mortality, colectomy, cancer, and hospitalisation represent hard outcomes of disease. Moreover, knowledge on the risk of relapses and need for potent medication add important information about living with UC. We aimed to evaluate the course and prognosis of UC during the first 20 years after diagnosis, and to identify early prognostic risk factors. Methods: From 1990 to 1994, a population-based inception cohort of patients with inflammatory bowel disease was enrolled in South-Eastern Norway. A systematic follow-up [FU] was conducted at 1,5, 10, and 20 years after diagnosis. Clinical outcomes were recorded continuously, and possible relationships between early disease characteristics and outcomes were analysed using multiple regression analysis. Results: Among 519 UC patients, 119 died, 60 were lost to FU, and 340 were included in the FU cohort. The 20-year cumulative risk of colectomy was 13.0% (95% confidence interval [CI] [11.4-14.6]). Extensive colitis at diagnosis was independently associated with an increased risk of colectomy compared with proctitis (hazard ratio [HR] = 2].8, 95% CI [1.3-6.1]). In contrast, mucosal healing at 1-year FU was independently associated with reduced risk of colectomy [HR = 0.4, 95% CI [0.2-0.8]), and inversely associated with subsequent risk of relapse [adjusted HR = 0.5, 95% CI [0.3-0.7]). Conclusions: The overall risk of colectomy in our cohort was lower than expected from previous studies, although considerable for patients with extensive colitis at diagnosis. Early mucosal healing was associated with better disease outcomes 20 years after diagnosis.

• Frick, Rahel; Høydahl, Lene Støkken; Petersen, Jan; Pré, Fleur du; Kumari, Shraddha & Berntsen, Grete [Vis alle 20 forfattere av denne artikkelen] (2021). A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation. Science immunology. 6:eabg4925(62), s. 1–16. doi: 10.1126/sciimmunol.abg4925. Fulltekst i vitenarkiv Vis sammendrag

  Antibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation and may have therapeutic potential. Here, we generated human T cell receptor (TCR)–like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-α2 in celiac disease (CeD). Phage display selection combined with secondary targeted engineering was used to obtain highly specific antibodies with picomolar affinity. The crystal structure of a Fab fragment of the lead antibody 3.C11 in complex with HLA-DQ2.5:DQ2.5-glia-α2 revealed a binding geometry and interaction mode highly similar to prototypic TCRs specific for the same complex. Assessment of CeD biopsy material confirmed disease specificity and reinforced the notion that abundant plasma cells present antigen in the inflamed CeD gut. Furthermore, 3.C11 specifically inhibited activation and proliferation of gluten-specific CD4+ T cells in vitro and in HLA-DQ2.5 humanized mice, suggesting a potential for targeted intervention without compromising systemic immunity.

• Kristensen, Vendel Ailin; Volkmann, Hilde Løland Von; Østvik, Ann Elisabet & Jahnsen, Jørgen (2021). Medisinsk behandling av Crohns sykdom. NGF-nytt. ISSN 0809-6570. 28(4), s. 8–13. Fulltekst i vitenarkiv
• Kalla, Rahul; Adams, Alex T.; Bergemalm, Daniel; Vatn, Simen Svendsen; Kennedy, Nicholas A. & Ricanek, Petr [Vis alle 22 forfattere av denne artikkelen] (2020). Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease. Journal of Crohn's and Colitis. ISSN 1873-9946. s. 1–33. doi: 10.1093/ecco-jcc/jjaa230. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. Methods We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. Results A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10–23] and oncostatin-M [OSM; p = 3.7 × 10–16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224–756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43–6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn’s disease respectively. Conclusion We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

• Opheim, Randi; Moum, Bjørn; Grimstad, Tore; Jahnsen, Jørgen; Berset, Ingrid Prytz & Hovde, Øistein [Vis alle 9 forfattere av denne artikkelen] (2020). Self-esteem in patients with inflammatory bowel disease. Quality of Life Research. ISSN 0962-9343. 29(7), s. 1839–1846. doi: 10.1007/s11136-020-02467-9. Fulltekst i vitenarkiv Vis sammendrag

  Purpose The purpose of this study was to explore self-esteem and associations between self-esteem and sociodemographic, clinical, and psychological factors in patients with infammatory bowel disease (IBD), a disease of chronic relapsing infammation of the gastrointestinal tract. IBD symptoms, including pain, fatigue, and diarrhea, as well as potential life-long medical treatment and surgery, may be demanding, cause signifcant challenges, and infuence self-esteem. Methods In this cross-sectional multicenter study, participants were recruited from nine hospitals in the southeastern and western regions of Norway from March 2013 to April 2014. Data were collected using self-report questionnaires. Selfesteem was assessed by the Rosenberg Self-Esteem Scale, fatigue was assessed by the Fatigue Questionnaire, self-efcacy was assessed by the General Self-Efcacy Scale, and disease activity was assessed by the Simple Clinical Colitis Activity Index for ulcerative colitis (UC) and Harvey Bradshaw Index for Crohn’s disease (CD). Multiple linear regression analysis was applied to examine associations between self-esteem and sociodemographic, clinical, and psychological factors. Results In total, 411 of 452 (91%) patients had evaluable data and were included in this study. The mean scores on selfesteem, self-efcacy, total fatigue, anxiety, and depression were similar between UC patients and CD patients. Male gender, being employed, and higher self-efcacy were independently associated with higher self-esteem, whereas anxiety and depression were independently associated with lower self-esteem. Neither disease activity nor fatigue were associated with self-esteem in the fnal multiple regression analyses. Conclusion Patient-centered interventions that improve self-esteem and reduce anxiety and depression seem to be important to optimize IBD management. Keywords Self-esteem · Self-efcacy · Coping · Infammatory bowel disease · Ulcerative colitis · Crohn’s disease · Health psychology · Chronic disease · Health-related quality of life

• Kim, HoUng; Alten, Rieke; Avedano, Luisa; Dignass, Axel; Gomollón, Fernando & Greveson, Kay [Vis alle 19 forfattere av denne artikkelen] (2020). The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases. Drugs. ISSN 0012-6667. 80(2), s. 99–113. doi: 10.1007/s40265-020-01256-5. Fulltekst i vitenarkiv Vis sammendrag

  Biologics have transformed the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Biosimilars—biologic medicines with no clinically meaningful differences in safety or efficacy from licensed originators—can stimulate market competition and have the potential to expand patient access to biologics within the parameters of treatment recommendations. However, maximizing the benefits of biosimilars requires cooperation between multiple stakeholders. Regulators and developers should collaborate to ensure biosimilars reach patients rapidly without compromising stringent quality, safety, or efficacy standards. Pharmacoeconomic evaluations and payer policies should be updated following biosimilar market entry, minimizing the risk of imposing nonmedical barriers to biologic treatment. In RA, disparities between treatment guidelines and national reimbursement criteria could be addressed to ensure more uniform patient access to biologics and enable rheumatologists to effectively implement treat-to-target strategies. In IBD, the cost-effectiveness of biologic treatment earlier in the disease course is likely to improve when biosimilars are incorporated into pharmacoeconomic analyses. Patient understanding of biosimilars is crucial for treatment success and avoiding nocebo effects. Full understanding of biosimilars by physicians and carefully considered communication strategies can help support patients initiating or switching to biosimilars. Developers must operate efficiently to be sustainable, without undermining product quality, the reliability of the supply chain, or pharmacovigilance. Developers should also facilitate information sharing to meet the needs of other stakeholders. Such collaboration will help to ensure a sustainable future for both the biosimilar market and healthcare systems, supporting the availability of effective treatments for patients.

• Klepp, Pasquale Catherine; Brackmann, Stephan; Småstuen, Milada Cvancarova; Høivik, Marte Lie; Hovde, Øistein & Henriksen, Magne [Vis alle 15 forfattere av denne artikkelen] (2020). Risk of colorectal cancer in a population-based study 20 years after diagnosis of ulcerative colitis: results from the IBSEN study. BMJ open gastroenterology. 7. doi: 10.1136/bmjgast-2019-000361. Fulltekst i vitenarkiv Vis sammendrag

  Objective The association between ulcerative colitis (UC) and colorectal cancer (CRC) is widely accepted, although attenuated risk has been reported in recent years. Colonoscopic surveillance is recommended with intervals based on established clinical risk factors. Nevertheless, a significant number of patients develop interval cancers, indicating the need of improved individualised assessment. In the present study, we evaluated clinical risk factors associated with CRC during a prescheduled follow-up 20 years after diagnosis, the IBSEN study. Design A population-based inception cohort of patients diagnosed with inflammatory bowel disease from 1 January 1990 until 31 December 1993, prospectively followed at 1, 5, 10 and 20 years after diagnosis. A total of 517 patients with UC were included; 264 (51 %) men; median age at inclusion 37.4 years (4–88). Results The overall incidence of CRC was 1.6% (8/517) at a 20-year follow-up. The total lifetime risk of CRC prior to or after UC diagnosis was 2.3%. (12/517). Patients older than 70 years at diagnosis had a 15-fold higher risk of CRC compared with those diagnosed when younger than 40 years, with HR 15.68 (95% CI: 1.31 to 187.92). Neither sex, first-degree relative with CRC, extent of colitis nor primary sclerosing cholangitis affected the risk of CRC. Conclusion The risk of CRC in UC was low and comparable with the risk of CRC in the background population of Norway.

• Kalla, Rahul; Adams, Alex T.; Ventham, Nicholas T.; Kennedy, Nicholas A.; White, R. & Clark, C [Vis alle 21 forfattere av denne artikkelen] (2020). Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease. Journal of Crohn's and Colitis. ISSN 1873-9946. 14(12), s. 1724–1733. doi: 10.1093/ecco-jcc/jjaa134. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. Methods In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn’s disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. Results In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20–3.27; logrank p = 1.80 × 10–3), in particular CD [HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. Interpretation We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

• Vatn, Simen Svendsen; Carstens, Adam; Kristoffersen, Anja Bråthen; Bergemalm, Daniel; Casen, Christina & Moen, Aina Elisabeth Fossum [Vis alle 19 forfattere av denne artikkelen] (2020). Faecal microbiota signatures of IBD and their relation to diagnosis, disease phenotype, inflammation, treatment escalation and anti-TNF response in a European Multicentre Study (IBD-Character). Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 55(10), s. 1146–1156. doi: 10.1080/00365521.2020.1803396. Fulltekst i vitenarkiv Vis sammendrag

  Method We examined faecal samples, using the GA-map™ Dysbiosis Test, to associate gut microbiota composition with Crohn’s disease (CD) and ulcerative colitis (UC) and to identify markers for future biomarker identification. We conducted a prospective case-control study (EU-ref. no. 305676) in an inception cohort of 324 individuals (64 CD, 84 UC, 116 symptomatic non-IBD controls and 44 healthy controls) across five European centres and examined 54 predetermined bacterial markers. We categorized patients according to the Montreal Classification and calculated the dysbiosis index (DI). Non-parametric tests were used to compare groups and the Bonferroni correction to adjust for multiple comparisons. Results The fluorescent signals (FSSs) for Firmicutes and Eubacterium hallii were lower in inflammatory bowel disease (IBD) vs. symptomatic controls (p<.05). FSS for Firmicutes, Lachnospiraceae, Eubacterium hallii and Ruminococcus albus/bromii were lower, whereas the signal for Bacteroides Fragilis was higher in UC vs. symptomatic controls (p<.05). FSS was higher for Bifidobacterium spp., Eubacterium hallii, Actinobacteria and Firmicutes among patients with ulcerative proctitis, compared to extensive colitis (p<.05). In CD, we observed no association with disease location. The DI correlated with faecal-calprotectin in both CD and in UC (p<.001). In terms of treatment escalation and anti-TNF response, differences were observed for some bacterial markers, but none of these associations were statistically significant. Conclusion Our data reveal that the GA-map™ Dysbiosis Test holds the potential to characterize the faecal microbiota composition and to assess the degree of dysbiosis in new-onset IBD. On the other hand, our results cannot demonstrate any proven diagnostic or predictive value of this method to support clinical decision making.

• Syversen, Silje Watterdal; Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Olsen, Inge Christoffer; Sandanger, Øystein & Gehin, Johanna Elin [Vis alle 13 forfattere av denne artikkelen] (2020). Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (The NOR-DRUM study). Trials. 21(13). doi: 10.1186/s13063-019-3734-4. Fulltekst i vitenarkiv Vis sammendrag

  Background Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B). Methods The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn’s disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period. Discussion As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines. Trial registration Clinicaltrials.gov, NCT03074656. Registered on 090317.

• Frigstad, Svein Oskar; Høivik, Marte Lie; Jahnsen, Jørgen; Småstuen, Milada C; Grimstad, Tore & Berset, Ingrid Prytz [Vis alle 11 forfattere av denne artikkelen] (2020). Pain Severity and Vitamin D Deficiency in IBD Patients. Nutrients. 12(1), s. 1–12. doi: 10.3390/nu12010026. Fulltekst i vitenarkiv Vis sammendrag

  Background: Pain and vitamin D deficiency are common in inflammatory bowel disease (IBD). Disease activity, fatigue, frequent relapses, prior surgery and psychological factors all seem to influence the experience of pain in IBD. Vitamin D deficiency has been associated with muscle and skeletal pain. This study aimed to determine whether there is an association between vitamin D deficiency and severity of pain in patients with IBD, and to investigate the influence of other socio-demographic and psychological variables on the experience of pain. Methods: Patients with IBD were recruited from nine hospitals in Norway in a multicenter cross-sectional study. The Brief Pain Inventory (BPI) questionnaire was used to measure pain. Disease activity was assessed using clinical disease activity indices, C-reactive protein (CRP) and fecal calprotectin. Regression models were fitted to explore a possible association between 25-hydroxyvitamin D and pain severity. Results: Of 407 patients included in the analyses, 229 (56%) had Crohn's disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency was present in half (203/407) of patients. Presence of pain was reported by 76% (309/407). More severe pain was associated with female gender and increased disease activity scores, but not with increased CRP or fecal calprotectin. In CD, patients without prior intra-abdominal surgery reported more severe pain. In multivariate analyses, there was no association between 25-hydroxyvitamin D and pain severity. Conclusions: In this study, no significant association between pain severity and vitamin D deficiency was revealed in patients with IBD. Keywords: pain severity; patient reported outcomes; vitamin D deficiency.

• Olbjørn, Christine; Rove, Jon Berggren & Jahnsen, Jørgen (2020). Combination of Biological Agents in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series and Review of the Literature. Pediatric Drugs. ISSN 1174-5878. 22(4), s. 409–416. doi: 10.1007/s40272-020-00396-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Treatment with biological agents such as anti-tumor necrosis factors (TNFs) has become standard of care in moderate to severe pediatric inflammatory bowel disease (IBD). However, a significant proportion of patients experience loss of response to anti-TNFs, need treatment escalation, or develop side effects. There is no data in the literature regarding combination of biological agents in pediatric IBD. Methods At our hospital, which is a tertiary referral center, we have combined the anti-TNF infliximab with either vedolizumab or ustekinumab in patients with severe pediatric IBD. The indications for dual biological therapy were insufficient efficacy of infliximab or vedolizumab monotherapy, or side effects such as psoriasis due to anti-TNFs. Results Eight patients (four boys) aged 14–17.5 years received a combination of infliximab and vedolizumab due to only a partial response to infliximab, four with Crohn’s disease (CD) and four with ulcerative colitis (UC). Clinical remission was achieved in four patients (3 UC) and four had a colectomy (3 CD, 1 UC). Five CD patients (3 girls) aged 11–17 years, on maintenance therapy with infliximab, developed psoriasis resistant to topical treatment. A combination of infliximab and ustekinumab resulted in clinical remission of CD without skin symptoms. No serious adverse events occurred in any of the patients on combination therapy. Thirteen publications report on combining biologicals, all in adult IBD. Conclusion In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The safety should be addressed in long-term follow-up studies.

• Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Sexton, Joseph; Bolstad, Nils; Olsen, Inge Christoffer & Asak, Øivind Wessel [Vis alle 29 forfattere av denne artikkelen] (2020). Efficacy and safety of CT-P13 in inflammatory bowel disease after switching from originator infliximab: Exploratory analyses from the NOR-SWITCH main and extension trials. BioDrugs. ISSN 1173-8804. 34(5), s. 681–694. doi: 10.1007/s40259-020-00438-7. Fulltekst i vitenarkiv Vis sammendrag

  Background: The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested. Objective: The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials. Patients and methods: The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period. Results: The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events. Conclusion: Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC.

• Hewitt, Stephen I; Kristinsson, Jon Adalsteinn; Aasheim, Erlend T.; Høgestøl, Ingvild Kristine; Aaseth, Eirik & Jahnsen, Jørgen [Vis alle 8 forfattere av denne artikkelen] (2020). Relationships Between Vitamin D Status and PTH over 5 Years After Roux-en-Y Gastric Bypass: a Longitudinal Cohort Study. Obesity Surgery. ISSN 0960-8923. 30(9), s. 3426–3434. doi: 10.1007/s11695-020-04582-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose Secondary hyperparathyroidism (SHPT) after obesity surgery may affect bone health. Optimal vitamin D levels have not been established to prevent SHPT postoperatively. We investigated whether SHPT differed across threshold levels of serum 25-hydroxyvitamin D (S-25(OH)D) from 6 months up to 5 years after Roux-en-Y gastric bypass (RYGB). Materials and Methods We included 554 patients at follow-up 5 years postoperatively. Blood samples were analysed for S-25(OH)D, ionized calcium (iCa) and parathyroid hormone (PTH) during follow-up. Results PTH and prevalence of SHPT increased from 6 months to 5 years postoperatively, while S-25(OH)D and iCa decreased (all P < 0.001). PTH and SHPT development are related with S-25(OH)D, and PTH differed between all subgroups of S-25(OH)D. SHPT occurred less frequently across all subgroups of S-25(OH)D ≥ 50 nmol/l during follow-up: odds ratio (OR) 0.44 (95% CI 0.36–0.54) in patients with S-25(OH)D ≥ 50 nmol/l, OR 0.38 (0.30–0.49) with S-25(OH)D ≥ 75 nmol/l and OR 0.19 (0.12–0.31) with S-25(OH) D ≥ 100 nmol/l, all compared with S-25(OH)D < 50 nmol/l. At 5 years, 208/554 patients (38%) had SHPT; SHPT was found in 94/188 patients (50%) with S-25(OH)D < 50 nmol/l, in 69/222 (31%) with S-25(OH)D 50–74 nmol/l, in 40/117 (34%) with S-25(OH)D 75–99 nmol/l and in 5/27 (19%) with S-25(OH)D ≥ 100 nmol/l. An interaction existed between S-25(OH)D and iCa. Bone alkaline phosphatase remained increased with SHPT. Conclusions A significant relationship existed between S-25(OH)D and development of PTH and SHPT. The prevalence of SHPT was lower with threshold levels 25(OH)D ≥ 50 nmol/l and ≥ 75 nmol/l over the 5 years, and lowest with S-25(OH)D ≥ 100 nmol/l. Keywords Bariatric surgery . Morbid obesity . Vitamin D . Calcium . Parathyroid hormone . Bone turnover

• Romstad, Kartine Maria Kauczynska; Detlie, Trond Espen; Søberg, Taran; Ricanek, Petr; Jahnsen, Marte Eide & Lerang, Frode [Vis alle 7 forfattere av denne artikkelen] (2020). Gastrointestinal bleeding due to peptic ulcers and erosions - a prospective observational study (BLUE study). Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 55(10), s. 1139–1145. doi: 10.1080/00365521.2020.1819405. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Acute upper gastrointestinal bleeding is a well-recognized complication of peptic ulcers and erosions. The aim of this study was to assess the incidence rate and identify risk factors for this complication in southeastern Norway. Materials and methods Between March 2015 and December 2017, a prospective observational study was conducted at two Norwegian hospitals with a total catchment area of approximately 800,000 inhabitants. Information regarding patient characteristics, comorbidities, drug use, H. pylori status and 30-day mortality was recorded. Results A total of 543 adult patients were included. The incidence was 30/100,000 inhabitants per year. Altogether, 434 (80%) of the study patients used risk medication. Only 46 patients (8.5%) used proton pump inhibitors (PPIs) for more than 2 weeks before the bleeding episode. H. pylori testing was performed in 527 (97%) patients, of whom 195 (37%) were H. pylori-positive. The main comorbidity was cardiovascular disease. Gastric and duodenal ulcers were found in 183 (34%) and 275 (51%) patients, respectively. Simultaneous ulcerations at both locations were present in 58 (10%) patients, and 27 (5%) had only erosions. Overall, the 30-day mortality rate was 7.6%. Conclusions The incidence of upper gastrointestinal bleeding due to peptic ulcers and erosions was found to be lower than previously demonstrated in comparable studies, but the overall mortality rate was unchanged. The consumption of risk medication was high, and only a few patients had used prophylactic PPIs. Concurrent H. pylori infection was present in only one-third of the patients.

• Ossum, Alvilde Maria; Palm, Øyvind; Småstuen, Milada C; Bernklev, Tomm; Jahnsen, Jørgen & Moum, Bjørn [Vis alle 7 forfattere av denne artikkelen] (2020). The Impact of Spondyloarthritis and Joint Symptoms on Health-Related Quality of Life and Fatigue in IBD Patients. Results from a Population-Based Inception Cohort (20-Year Follow-up in the Ibsen Study). Inflammatory Bowel Diseases. ISSN 1078-0998. doi: 10.1093/ibd/izz105. Fulltekst i vitenarkiv Vis sammendrag

  Background: Patients with inflammatory bowel disease (IBD) often suffer from musculoskeletal manifestations. Health-related quality of life (HRQoL) and fatigue are known to be associated with IBD activity and musculoskeletal complaints. The aim of this study was to determine the association between spondyloarthritis, arthralgia, or back pain and the patient-reported outcomes of HRQoL and fatigue in IBD patients 20 years after their diagnosis. Methods: The IBSEN cohort was followed prospectively for 20 years. At the 20-year follow-up, the patients answered detailed questionnaires regarding rheumatological manifestations, intestinal symptoms, HRQoL, and fatigue. Multiple regression analyses were used to evaluate associations between spondyloarthritis or joint symptoms and HRQoL or fatigue. Sex, IBD diagnosis, and age were included in all the multiple regression models, in addition to other clinically relevant confounders. Results: In total, 441 patients (94%) completed the questionnaires at the 20-year follow-up. The criteria for spondyloarthritis (axial or peripheral) were fulfilled in 158 patients (36%), current back pain during the previous 3 months was reported by 79 patients (18%), and current arthralgia was reported by 178 patients (40%). Current back pain and arthralgia were independently associated with lower HRQoL, higher levels of fatigue, and chronic fatigue. A diagnosis of spondyloarthritis was not associated with reduced HRQoL or fatigue when adjusted for possible confounders. Conclusions: Current joint symptoms in IBD patients 20 years after diagnosis were associated with poorer HRQoL, higher levels of fatigue, and chronic fatigue, whereas spondyloarthritis did not impact HRQoL or fatigue negatively in this cohort.

• Kristensen, Vendel Ailin; Valeur, Jørgen; Brackmann, Stephan; Jahnsen, Jørgen; Brunborg, Cathrine & Tveito, Kari (2019). Attention deficit and hyperactivity disorder symptoms respond to gluten-free diet in patients with coeliac disease. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 54(5), s. 571–576. doi: 10.1080/00365521.2019.1608467. Fulltekst i vitenarkiv
• Lunder, Aida Kapic; Bakstad, Linda Tøften; Jahnsen, Jørgen; Borthne, Arne Sigmund; Hov, Johannes Espolin Roksund & Vatn, Morten H [Vis alle 7 forfattere av denne artikkelen] (2019). Assessment of Bowel Inflammation and Strictures by Magnetic Resonance Enterography in Long-term Crohn´s Disease. Journal of Crohn's and Colitis. ISSN 1873-9946. 13(5), s. 607–614. doi: 10.1093/ecco-jcc/jjy208. Fulltekst i vitenarkiv
• Olbjørn, Christine; Småstuen, Milada Cvancarova; Thiis-Evensen, Espen; Nakstad, Britt; Vatn, Morten H & Jahnsen, Jørgen [Vis alle 20 forfattere av denne artikkelen] (2019). Fecal microbiota profiles in treatment-naive pediatric inflammatory bowel disease ? associations with disease phenotype, treatment, and outcome. Clinical and Experimental Gastroenterology. 12, s. 37–49. doi: 10.2147/CEG.S186235. Fulltekst i vitenarkiv Vis sammendrag

  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 (P<0.001). Only Prevotella was more abundant in patients (P<0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (P<0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (P<0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (P<0.01), and nonmucosal healing (P<0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (P<0.03). After therapy, IBD patients had unchanged dysbiosis. Conclusion: 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.

• Goll, Guro Løvik; Jørgensen, Kristin Kaasen; Sexton, Joseph; Olsen, Inge Christoffer; Bolstad, Nils & Haavardsholm, Espen A. [Vis alle 48 forfattere av denne artikkelen] (2019). Long‐term efficacy and safety of biosimilar infliximab (CT‐P13) after switching from originator infliximab: Open‐label extension of the NOR‐SWITCH trial. Journal of Internal Medicine. ISSN 0954-6820. 285(6), s. 653–669. doi: 10.1111/joim.12880. Fulltekst i vitenarkiv Vis sammendrag

  Background and objectives The 52‐week, randomized, double‐blind, noninferiority, government‐funded NOR‐SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT‐P13 was not inferior to continued treatment with infliximab originator. The NOR‐SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT‐P13 throughout the 78‐week study period (maintenance group) versus patients switched to CT‐P13 at week 52 (switch group). The primary outcome was disease worsening during follow‐up based on disease‐specific composite measures. Methods Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. Results Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per‐protocol set). Adjusted risk difference was 5.9% (95% CI −1.1 to 12.9). Frequency of adverse events, anti‐drug antibodies, changes in generic disease variables and disease‐specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. Conclusion The NOR‐SWITCH extension showed no difference in safety and efficacy between patients who maintained CT‐P13 and patients who switched from originator infliximab to CT‐P13, supporting that switching from originator infliximab to CT‐P13 is safe and efficacious.

• Dahal-Koirala, Shiva; Neumann, Ralf Stefan; Jahnsen, Jørgen; Lundin, Knut Erik Aslaksen & Sollid, Ludvig Magne (2019). On the immune response to barley in celiac disease: Biased and public T-cell receptor usage to a barley unique and immunodominant gluten epitope. European Journal of Immunology. ISSN 0014-2980. s. 1–14. doi: 10.1002/eji.201948253. Fulltekst i vitenarkiv Vis sammendrag

  Celiac disease (CeD) is driven by CD4+ T‐cell responses to dietary gluten proteins of wheat, barley, and rye when deamidated gluten epitopes are presented by certain disease‐associated HLA‐DQ allotypes. About 90% of the CeD patients express HLA‐DQ2.5. In such patients, five gluten epitopes dominate the anti‐gluten T‐cell response; two epitopes unique to wheat, two epitopes present in wheat, barley, and rye and one epitope unique to barley. Despite presence of barley in commonly consumed food and beverages and hence being a prominent source of gluten, knowledge about T‐cell responses elicited by barley in CeD is scarce. Therefore, in this study, we explored T‐cell response toward the barley unique epitope DQ2.5‐hor‐3 (PIPEQPQPY) by undertaking HLA‐DQ:gluten peptide tetramer staining, single‐cell T‐cell receptor (TCR) αβ sequencing, T‐cell cloning, and T‐cell proliferation studies. We demonstrate that majority of the CeD patients generate T‐cell response to DQ2.5‐hor‐3, and this response is characterized by clonal expansion, preferential TCR V‐gene usage and public TCR features thus echoing findings previously made for wheat gluten epitopes. The knowledge that biased and public TCRs underpin the T‐cell response to all the immunodominant gluten epitopes in CeD suggests that such T cells are promising diagnostic and therapeutic targets.

• Detlie, Trond Espen; Lindstrøm, Jonas Christoffer; Jahnsen, Marte Eide; Finnes, Elisabeth; Zoller, Heinz & Moum, Bjørn [Vis alle 7 forfattere av denne artikkelen] (2019). Incidence of hypophosphatemia in patients with inflammatory bowel disease treated with ferric carboxymaltose or iron isomaltoside. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 50(4), s. 397–406. doi: 10.1111/apt.15386. Fulltekst i vitenarkiv Vis sammendrag

  Background: Iron deficiency and iron deficiency anaemia are common complications in inflammatory bowel disease (IBD). In patients with moderate‐to‐severe anaemia, oral iron intolerance or ineffectiveness of oral iron, ferric carboxymaltose and iron isomaltoside are widely used. Hypophosphatemia is a side effect of both preparations. Aims: To investigate the occurrence of hypophosphatemia in IBD patients with iron deficiency/iron deficiency anaemia treated with high‐dose intravenous iron. Methods: A prospective observational study of adult IBD patients with iron deficiency/iron deficiency anaemia was conducted at two study sites where patients received 1000 mg of ferric carboxymaltose or iron isomaltoside. At baseline, weeks 2 and 6, blood and faecal samples were collected. The primary endpoint was to determine the incidence of moderate‐to‐severe hypophosphatemia. Secondary endpoints included the total incidence of hypophosphatemia, possible risk factors for hypophosphatemia, and response to single‐dose intravenous iron. Results: One hundred and thirty patients were included. In the per‐protocol set, 52 patients received ferric carboxymaltose and 54 patients received iron isomaltoside. Ferric carboxymaltose treatment had a significantly higher incidence of moderate‐to‐severe hypophosphatemia compared with iron isomaltoside at week 2 (56.9% vs 5.7%, P < 0.001) and a higher incidence at week 6 (13.7% vs 1.9%, P = 0.054).The overall incidence of hypophosphatemia was significantly higher with ferric carboxymaltose compared with iron isomaltoside treatment at weeks 2 (72.5% vs 11.3%, P < 0.001) and 6 (21.6% vs 3.7%, P = 0.013). Conclusions: In IBD patients with iron deficiency/iron deficiency anaemia, ferric carboxymaltose was associated with higher incidence, severity and persistence of hypophosphatemia compared with iron isomaltoside. The presence of moderate‐to‐severe hypophosphatemia beyond 6 weeks is a clinical concern that requires further investigation.

• Høydahl, Lene Støkken; Richter, Lisa Maria; Frick, Rahel; Snir, Omri; Gunnarsen, Kristin Støen & Landsverk, Ole J. B. [Vis alle 18 forfattere av denne artikkelen] (2018). Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease. Gastroenterology. ISSN 0016-5085. 156(5), s. 1428–1439.e10. doi: 10.1053/j.gastro.2018.12.013. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims Development of celiac disease is believed to involve the transglutaminase-dependent response of CD4+ T cells toward deamidated gluten peptides in the intestinal mucosa of individuals with specific HLA-DQ haplotypes. We investigated the antigen presentation process during this mucosal immune response. Methods We generated monoclonal antibodies (mAbs) specific for the peptide–MHC (pMHC) complex of HLA-DQ2.5 and the immunodominant gluten epitope DQ2.5-glia-α1a using phage display. We used these mAbs to assess gluten peptide presentation and phenotypes of presenting cells by flow cytometry and enzyme-linked immune absorbent spot (ELISPOT) in freshly prepared single-cell suspensions from intestinal biopsies from 40 patients with celiac disease (35 untreated and 5 on a gluten-free diet) as well as 18 subjects with confirmed noninflamed gut mucosa (controls, 12 presumed healthy, 5 undergoing pancreatoduodenectomy, and 1 with potential celiac disease). Results Using the mAbs, we detected MHC complexes on cells from intestinal biopsies from patients with celiac disease who consume gluten, but not from patients on gluten-free diets. We found B cells and plasma cells to be the most abundant cells that present DQ2.5-glia-α1a in the inflamed mucosa. We identified a subset of plasma cells that expresses B-cell receptors (BCR) specific for gluten peptides or the autoantigen transglutaminase 2 (TG2). Expression of MHC class II (MHCII) was not restricted to these specific plasma cells in patients with celiac disease but was observed in an average 30% of gut plasma cells from patients and controls. Conclusions A population of plasma cells from intestinal biopsies of patients with celiac disease express MHCII; this is the most abundant cell type presenting the immunodominant gluten peptide DQ2.5-glia-α1a in the tissues from these patients. These results indicate that plasma cells in the gut can function as antigen-presenting cells and might promote and maintain intestinal inflammation in patients with celiac disease or other inflammatory disorders.

• Hewitt, Stephen I; AASHEIM, ERLEND T.; Søvik, Torgeir Thorson; Jahnsen, Jørgen; Kristinsson, Jon Adalsteinn & Eriksen, Erik Fink [Vis alle 7 forfattere av denne artikkelen] (2018). Relationships of serum 25-hydroxyvitamin D, ionized calcium and parathyroid hormone after obesity surgery. Clinical Endocrinology. ISSN 0300-0664. 88(3), s. 372–379. doi: 10.1111/cen.13531. Fulltekst i vitenarkiv
• Kapica, Aida; Jahnsen, Jørgen; Bakstad, Linda Tøften; Borthne, Arne Sigmund; Hov, Johannes Espolin Roksund & Vatn, Morten H [Vis alle 7 forfattere av denne artikkelen] (2018). Bowel Damage in Patients With Long-term Crohn's Disease, Assessed by Magnetic Resonance Enterography and the Lemann Index. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 16(1), s. 75–82.e5. doi: 10.1016/j.cgh.2017.06.053. Fulltekst i vitenarkiv
• Frigstad, Svein Oskar; Høivik, Marte Lie; Jahnsen, Jørgen; Småstuen, Milada Cvancarova; Grimstad, Tore & Berset, Ingrid Prytz [Vis alle 11 forfattere av denne artikkelen] (2018). Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 24(29), s. 3293–3301. doi: 10.3748/wjg.v24.i29.3293. Fulltekst i vitenarkiv Vis sammendrag

  AIM To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease (IBD). METHODS IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire (FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance. RESULTS In total, 405 patients were included in the analyses, of which 227 (56%) had Crohn’s disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency (< 50 nmol/L) was present in half (203/405) of the patients. Chronic fatigue was reported by 116 (29%) of all included patients with substantial fatigue reported by 194 (48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients. CONCLUSION In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed. Key Words: Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis, Fatigue, Chronic fatigue, Vitamin D deficiency Core tip: Fatigue is common in inflammatory bowel diseases (IBD) and is especially prevalent in active disease. We wanted to investigate if vitamin D deficiency was associated to fatigue in IBD as this is a common belief among both patients and physicians. To the best of our knowledge, no previous studies have investigated this possible association in IBD patients. We also wanted to take into account the multidimensional approach in understanding fatigue making it difficult to single out any one contributing factor. In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.

• Moen, Aina Elisabeth Fossum; Lindstrøm, Jonas Christoffer; Tannæs, Tone Møller; Vatn, Simen Svendsen; Ricanek, Petr & Vatn, Morten H [Vis alle 8 forfattere av denne artikkelen] (2018). The prevalence and transcriptional activity of the mucosal microbiota of ulcerative colitis patients. Scientific Reports. 8:17278. doi: 10.1038/s41598-018-35243-4. Fulltekst i vitenarkiv Vis sammendrag

  Active microbes likely have larger impact on gut health status compared to inactive or dormant microbes. We investigate the composition of active and total mucosal microbiota of treatment-naïve ulcerative colitis (UC) patients to determine the microbial picture at the start-up phase of disease, using both a 16S rRNA transcript and gene amplicon sequencing. DNA and RNA were isolated from the same mucosal colonic biopsies. Our aim was to identify active microbial members of the microbiota in early stages of disease and reveal which members are present, but do not act as major players. We demonstrated differences in active and total microbiota of UC patients when comparing inflamed to non-inflamed tissue. Several taxa, among them the Proteobacteria phyla and families therein, revealed lower transcriptional activity despite a high presence. The Bifidobacteriaceae family of the Actinobacteria phylum showed lower abundance in the active microbiota, although no difference in presence was detected. The most abundant microbiota members of the inflamed tissue in UC patients were not the most active. Knowledge of active members of microbiota in UC patients could enhance our understanding of disease etiology. The active microbial community composition did not deviate from the total when comparing UC patients to non-IBD controls.

• Sunde, Marie Louise; Ricanek, Petr; Øresland, Tom; Jahnsen, Jørgen; Naimy, Nazir & Færden, Arne Engebreth (2018). Determinants of optimal bowel function in ileal pouch-anal-anastomosis - physiological differences contributing to pouch function. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 53(1), s. 8–14. doi: 10.1080/00365521.2017.1390601. Fulltekst i vitenarkiv
• Kalla, Rahul; Boyapati, Ray; Vatn, Simen Svendsen; Hijos, Gonzalo; Crooks, Benjamin & Moore, Gregory Thomas [Vis alle 11 forfattere av denne artikkelen] (2018). Patients' perceptions of faecal calprotectin testing in inflammatory bowel disease: results from a prospective multicentre patient-based survey. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 53(12), s. 1437–1442. doi: 10.1080/00365521.2018.1527394. Fulltekst i vitenarkiv
• Frigstad, Svein Oskar; Høivik, Marte; Jahnsen, Jørgen; Dahl, Sandra Rinne; Småstuen, Milada C & Grimstad, Tore [Vis alle 13 forfattere av denne artikkelen] (2017). Vitamin D deficiency in inflammatory bowel disease: Prevalence and predictors in a Norwegian outpatient population. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 52(1), s. 100–106. doi: 10.1080/00365521.2016.1233577. Fulltekst i vitenarkiv Vis sammendrag

  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 <50 nmol/L, including 53% (122/230) of the Crohn’s disease (CD) patients and 44% (78/178) of the ulcerative colitis (UC) patients. In CD patients, disease activity, measured as the HBI, was inversely associated with vitamin D deficiency. No such association was observed with the Simple Clinical Colitis Activity Index (SCCAI) scores in UC, but in UC patients, vitamin D deficiency was associated with elevated faecal calprotectin >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.

• Jelsness-Jørgensen, Lars-Petter; Frigstad, Svein Oskar; Moum, Bjørn; Grimstad, Tore; Opheim, Randi & Jahnsen, Jørgen [Vis alle 7 forfattere av denne artikkelen] (2017). Pain may be an important factor to consider in inflammatory bowel disease patients troubled by fatigue. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 5(5), s. 687–693. doi: 10.1177/2050640616674654. Fulltekst i vitenarkiv
• Reinisch, Walter W.; Jahnsen, Jørgen; Schreiber, Stefan; Danese, Silvio; Panés, Julián & Balsa, Alejandro [Vis alle 10 forfattere av denne artikkelen] (2017). Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged with Both Agents. BioDrugs. ISSN 1173-8804. 31(3), s. 223–237. doi: 10.1007/s40259-017-0219-4. Fulltekst i vitenarkiv
• Jahnsen, Jørgen & Jørgensen, Kristin Kaasen (2017). Experience with Biosimilar Infliximab (Remsima?) in Norway. Digestive Diseases. ISSN 0257-2753. 35(1-2), s. 83–90. doi: 10.1159/000449088. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Holly, Teresa; Brun, Marthe Kirkesæther; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Sexton, Joseph & Gehin, Johanna [Vis alle 16 forfattere av denne artikkelen] (2025). Cost-effectiveness of proactive therapeutic drug monitoring (TDM) in patients with inflmmatory disease-results from the Nor-Drum trial. Fulltekst i vitenarkiv
• Syversen, Silje Watterdal; Jahnsen, Jørgen & Haavardsholm, Espen A. (2022). Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy and Control of Immune-Mediated Inflammatory Diseases-Reply. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 327(15), s. 1506–1507. doi: 10.1001/jama.2022.2938. Fulltekst i vitenarkiv
• Mortensen, Joachim Høg; Lunder, Aida Kapic; Manon-Jensen, Tina; Karsdal, MA; Nielsen, Mette & Leeming, DJ [Vis alle 13 forfattere av denne artikkelen] (2020). P117 Biomarkers of extracellular matrix remodelling are associated with intestinal fibrosis assessed by magnetic resonance enterography and accumulated intestinal damage (Lémann index): the IBSEN study. Fulltekst i vitenarkiv
• Bjørlykke, Kristin Hammersbøen; Eftang, Lars Lohne; Grzyb, Krzysztof; Line, Pål Dag; Lassen, Kristoffer & Jahnsen, Jørgen (2020). A man in his fifties with abdominal pain, itching and weight loss. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.19.0390. Fulltekst i vitenarkiv
• Kim, HoUng; Alten, Rieke; Avedano, Luisa; Dignass, Axel; Gomollón, Fernando & Greveson, Kay [Vis alle 19 forfattere av denne artikkelen] (2020). Correction to: The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases. Drugs. ISSN 0012-6667. 80(10), s. 1039–1040. doi: 10.1007/s40265-020-01333-9. Fulltekst i vitenarkiv
• Detlie, Trond Espen & Jahnsen, Jørgen (2020). Editorial: improving precision of iron deficiency diagnosis in inflammatory bowel disease. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 52(2), s. 400–400. doi: 10.1111/apt.15809. Fulltekst i vitenarkiv
• Opheim, Randi; Jahnsen, Jørgen; Bernklev, Tomm; Høie, Ole Ingebreth; Huppertz-Hauss, Gert & Moum, Bjørn (2019). Complementary and alternative medicine in patients with inflammatory bowel disease 20 years after diagnosis: Results from the IBSEN study. American Journal of Gastroenterology. ISSN 0002-9270. 114, s. S12–S13. doi: 10.14309/01.ajg.0000578256.56976.23. Fulltekst i vitenarkiv
• Detlie, Trond Espen & Jahnsen, Jørgen (2019). Editorial: awareness and prevention of intravenous iron-induced hypophosphataemia. Authors' reply. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 50(5), s. 610–611. doi: 10.1111/apt.15443. Fulltekst i vitenarkiv
• Kristensen, Vendel Ailin; Valeur, Jørgen; Brackmann, Stephan; Jahnsen, Jørgen & Tveito, Kari (2019). Kognitive symptomer hos pasienter med cøliaki før og etter glutenfri kost. Fulltekst i vitenarkiv
• Opheim, Randi; Bernklev, Tomm; Jahnsen, Jørgen; Grimstad, Tore; Hovde, Øistein & Berset, Ingrid Prytz [Vis alle 8 forfattere av denne artikkelen] (2018). Chronic fatigue in patients with inflammatory bowel disease is associated with lower health–related quality of life, low self-esteem, increased anxiety and depression. Fulltekst i vitenarkiv
• Lunder, Aida Kapic; T, Linda Bakstad; Kapica, Aida; Jahnsen, Jørgen; Hov, Johannes Espolin Roksund & Borthne, Arne Sigmund [Vis alle 8 forfattere av denne artikkelen] (2018). Assessment of Inflammation by Magnetic Resonance Enterography in Long-term Crohn´s Disease. Fulltekst i vitenarkiv
• Moen, Aina Elisabeth Fossum; Lindstrøm, Jonas Christoffer; Tannæs, Tone Møller; Vatn, Simen Svendsen; Vatn, Morten H & Jahnsen, Jørgen [Vis alle 8 forfattere av denne artikkelen] (2018). Microbial expression in biopsies from ulcerative colitis at the time of diagnosis: bacterial activity is unrelated to abundancy. Fulltekst i vitenarkiv
• Frigstad, Svein Oskar; Bernklev, Tomm; Dahl, Sandra Rinne; Hovde, Øistein; Jahnsen, Jørgen & Grimstad, Tore [Vis alle 10 forfattere av denne artikkelen] (2017). Vitamin D deficiency is not associated with chronic fatigue in inflammatory bowel disease. Fulltekst i vitenarkiv
• Frigstad, Svein Oskar; Høivik, Marte Lie; Småstuen, Milada C; Jahnsen, Jørgen; Dahl, Sandra Rinne & Berset, Ingrid Prytz [Vis alle 13 forfattere av denne artikkelen] (2017). Fatigue er ikke assosiert med vitamin D mangel hos IBD pasienter. Fulltekst i vitenarkiv
• Jørgensen, Kristin Kaasen; Lundin, Knut Erik Aslaksen; Olsen, Inge Christoffer; Kvien, Tore Kristian & Jahnsen, Jørgen (2017). Efficacy of infliximab biosimilars in patients with Crohn's disease - Authors' reply. The Lancet. ISSN 0140-6736. 390(10111), s. 2436–2436. doi: 10.1016/S0140-6736(17)32463-7. Fulltekst i vitenarkiv
• Jørgensen, Kristin Kaasen; Christoffer, Olsen Inge; Goll, Guro Løvik; Lorentzen, Merete; Bolstad, Nils & Berset, Ingrid Prytz [Vis alle 11 forfattere av denne artikkelen] (2017). Biosimilar Infliximab (CT-P13) is not Inferior to Originator Infliximab: Explorative IBD Subgroup-Analyses in Crohn's Disease and Ulcerative Colitis from the Nor-Switch Trial. Gastroenterology. ISSN 0016-5085. 152(5), s. 65–66. doi: 10.1016/S0016-5085(17)30572-3. Fulltekst i vitenarkiv
• Lunder, Aida Kapic; Jahnsen, Jørgen; T, Linda Bakstad; Borthne, Arne Sigmund; Hov, Johannes Espolin Roksund & Vatn, Morten H [Vis alle 7 forfattere av denne artikkelen] (2017). Long-term Crohn's Disease Assessed by Magnetic Resonance Enterography and Lemann Index: Disease Extent and Bowel Damage in a Population Based Cohort. Fulltekst i vitenarkiv

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