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Background: Incidence rates of inflammatory bowel disease [IBD] reported from developed countries are rising, with some levelling out. The aim of this study was to assess the disease burden of IBD by estimating the incidence and prevalence across age groups and projecting these to 2030 in a high-incidence country., Methods: Using an algorithm [incorporating ICD codes, medications and histopathology], patients [n = 69 862] diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] between 1980 and 2017 were identified in the Danish National Patient Registry and included in a nationwide cohort., Results: From 1980 to 2017 the overall incidence of CD increased from 5.1 [95% CI: 4.5-5.8] to 15.6 [95% CI: 14.6-16.6] per 100 000, while the incidence of UC increased from 6.2 [95% CI: 5.5-6.9] to 27.2 [95% CI: 25.9-28.6] per 100 000. For paediatric-onset CD [pCD], the incidence increased from 1.9 [95% CI: 1.2-2.8] to 9.9 [95% CI: 8.1-11.8] per 100 000 and from 1.8 [95% CI: 1.2-2.8] to 8.7 [95% CI: 7.1- 10.5] per 100 000 for paediatric-onset UC [pUC]. In 2017, the prevalence of CD and UC was 293 [95% CI: 288-297] and 523 [95% CI: 517-528] per 100 000. For pCD and pUC, the prevalence was 35 [95% CI: 31-38] and 28 [95% CI: 26-32] per 100 000., Conclusions: The incidence of paediatric- and adult-onset IBD in Denmark continues to increase and is among the highest in the world., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment., Methods and Analysis: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis., Ethics and Dissemination: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences., Competing Interests: Competing interests: HRS: HRS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. JBS: Has received unrestricted research grants from Janssen and Takeda and is national coordinator of clinical trials from Boerhinger Ingelheim and Eli Lilly. JB: Personal fees from AbbVie, Janssen-Cilag, Celgene, Samsung Bioepis, and Pfizer; grants and personal fees from Takeda, MSD, and Tillots Pharma; grants from Novo Nordisk Foundation and Bristol Meyers Squibb., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Primary non-response to infliximab (IFX) inherits a poor prognosis in inflammatory bowel disease (IBD). We explored underlying mechanisms and therapeutic thresholds in an effort to provide basis for optimizing therapy., Methods: A prospectively followed cohort of 166 IBD patients having received standard IFX induction therapy (5 mg/kg at weeks 2, 6, and 14) had trough IFX and anti-IFX antibodies (Abs) retrospectively assessed at weeks 2 ( n  = 148) and 6 ( n  = 108). Circulating TNFα was measured in matched primary non-responders ( n  = 29) and responders ( n  = 21) at baseline and weeks 6 and 14. Clinical outcome at week 14 was supported by disease activity scores in half of patients., Results: In all, 18 patients (11%) had primary non-response. Infliximab was consistently lower throughout the induction phase in non-responders as compared to responders (Week 2: IFX median 18.9 μg/mL vs. 23.3, p  < .05. Week 6: 8.4 vs. 17.0, p  < .05). Optimal IFX thresholds associated with response was 22.9 μg/mL at week 2 (sensitivity 51%, specificity 80%, AUC ROC 0.67, p  < .05) and 11.8 at week 6 (72%, 77%, 0.71, p  < .05). Anti-IFX Abs occurred in 28% of primary non-responders and associated with low IFX and treatment failure (OR 13.7 [2.8-67.5], p  < .01). Markers of disease activity (disease activity scores, albumin, CRP) also associated with low IFX. Circulating TNFα was higher throughout induction in non-responders with ulcerative colitis but not Crohn's disease., Conclusion: IBD patients with primary IFX failure generally have lower IFX trough than responders during early induction phase. Pharmacokinetic failure seems common in ulcerative colits, whereas pharmacodynamic failure appears common in Crohn's disease.