The IBD-FITT study - moderate-intensity exercise for patients with inflammatory bowel disease with moderate disease activity: an open-label randomized controlled trial.

BACKGROUND: Inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients' general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). METHODS: We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60-80% of patients' maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15-25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). DISCUSSION: This will be a clinical trial investigating the effect of exercise on patients with Crohn's disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

Predictors of health-related quality of life in patients with Crohn's disease receiving biological therapy.

BACKGROUND AND AIM: Health-related quality of life (HRQoL) is impaired in patients with Crohn's disease (CD). This study aimed to identify the impact of clinical disease activity on HRQoL in CD patients treated with biological agents. METHODS: Patients with moderate to severe active CD treated with biological agents in Denmark were included from 2016-2018. Disease related symptoms were assessed via the Harvey Bradshaw Index. HRQoL was measured on the Short Health Scale (SHS). Multivariable linear regression models were conducted separately for each SHS item and average SHS score stratified for sex, adjusting for clinical manifestation and age. RESULTS: In total, 1,181 CD patients were included. The mean age was 33 years and 56% were women. Abdominal pain (range of regression coefficients 1.18-1.42), number of liquid stools (0.33-0.58), and the appearance of a new rectal fistula (0.91-1.32) affected all domains in the SHS negatively for men and women. Arthralgia (0.47-0.67) and abdominal mass (0.54-0.62) affected 4 out of 5 items on SHS negatively for women and men, respectively. Female sex was found a predictor of lower HRQoL across all SHS items, whereas age and fistulizing disease, as phenotype, were not associated with lower HRQoL. CONCLUSIONS: Abdominal pain, number of liquid stools, a new rectal fistula, arthralgia for women, clinically assessed abdominal mass for men as well as female sex, were all found to be predictors of decreased HRQoL.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Biologic therapy in inflammatory bowel disease.

In luminal Crohn's disease with moderate to severe inflammatory activity, infliximab and adalimumab can be used in the case of treatment failure with conventional therapies, such as systemic steroids and immunosuppressive therapy or if this treatment is not tolerated. Further treatment strategy depends on the primary response to induction therapy. Effect of maintenance therapy should be evaluated clinically and paraclinically at least every 26-52 weeks, and maybe supplemented by endoscopy or MRI scan. Decision of treatment discontinuation is based on disease manifestation, treatment response and paraclinical parameters. In fistulising Crohn's disease, treatment with infliximab or adalimumab can be initiated in simple fistula with rectal inflammation or complex fistula when the initial treatment has insufficient effect. Further treatment strategy depends on the primary response to induction therapy. Maintenance therapy is often necessary in complex fistulas. Treatment efficacy and possible discontinuation of treatment is evaluated at least every 26-52 weeks - if possibly with diagnostic imaging. In acute severe ulcerative colitis, treatment with infliximab can be used in patients with partial response after 3-5 days of treatment with a high-dose systemic steroid and when surgical treatment is not preferred or required. Further treatment strategy depends on the response to the first drug administration and colectomy should always be considered as an option. Effect of subsequent initiated maintenance therapy should be evaluated at least every 26-52 weeks on the basis of symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. In chronic active ulcerative colitis, infliximab and adalimumab can be used in the case of treatment with immunosuppressive therapy fails and if surgery is not preferred. Further treatment strategy depends on the response to induction therapy. Treatment efficacy is assessed by symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. Effect of maintenance therapy should be evaluated at least every 26-52 weeks. During treatment with biologic drugs focus should be on possible complications, such as infections, infusion or injection reactions and dermatological side effects. An overview of levels of evidence and recommendations is presented.

[Probiotics--should we change the treatment strategy for pouchitis?]. / Probiotika--skal vi aendre behandlingsstrategi for pouchitis?

Pouchitis is an idiopathic inflammatory bowel disease, which occurs in up to 50% of patients operated on for ulcerative colitis with ileal pouch-anal anastomosis (IPAA). Treatment of pouchitis is still to a large extent empirical, but recently more randomized, double-blind placebo-controlled trials have been conducted. This article reviews the possible treatments for pouchitis, focusing especially on treatment with probiotics, which seem to be a new and promising alternative to antibiotics. We are currently doing clinical trials to determine whether a probiotic is an effective treatment for chronic inflammatory bowel disease.