Chrohn's Disease

Crohn's disease is a long-term condition that causes inflammation in the bowel. Many people with Crohn's will need surgery at some point to remove damaged sections of intestine. Although surgery can improve symptoms, the disease often comes back near the join (anastomosis) where the bowel has been reconnected. Surgeons use different techniques to reconnect the bowel. One newer approach, called the Kono-S anastomosis, is designed to reduce the risk of Crohn's disease returning. Early results are promising, but it is still not fully understood why it may work better than traditional methods. This project aims to explore how the bowel heals after surgery by looking at oxidative stress, a type of tissue damage caused by an imbalance of harmful molecules in the body. The investigators will focus on a protective protein called glutathione peroxidase-4 (GPX4), an anti-oxidative enzyme that reduces oxidized phospholipids in biomembranes. By analysing tissue samples taken before and after surgery, the investigators will compare patients who had the Kono-S technique with those who had standard surgical joins. The investigators want to see whether differences in healing at a microscopic level could explain why some patients do better than others. The findings from this study could: * Improve understanding of why Crohn's disease comes back after surgery. * Help surgeons choose the best technique for each patient. * Support the development of new treatments aimed at improving healing. Ultimately, this research aims to reduce the risk of disease recurrence and improve long-term outcomes for people living with Crohn's disease.

This study will investigate in patients with Crohn s disease and ulcerative colitis how the body s immune system controls inflammation in the gastrointestinal tract (stomach and intestines)-specifically, how lymphocytes (a type of white blood cell) function in inflammatory responses. This protocol does not involve any experimental treatments. Patients between the ages of 0 and 75 years of age with Crohn s disease or ulcerative colitis or symptoms of inflammatory bowel disease may be eligible for this study. Screening tests may include the following: medical history and physical examination, routine blood tests, examination of stool specimens, X-rays such as barium enema or upper GI series, proctosigmoidoscopy, colonoscopy, gastroduodenoscopy, and small bowel biopsy. Participants will receive medical treatment according to the best generally accepted measures for treating Crohn s disease or ulcerative colitis. This may include anti-inflammatory drugs, immunosuppressive drugs, and antibiotics to treat infections. A surgical consultation may be recommended for patients whose disease does not respond to medical treatment. If surgery to remove intestinal tissue is recommended, a qualified gastrointestinal surgeon will perform the procedure. In addition, participants may undergo the following procedures: * Blood drawing - No more than 450 milliliters (30 tablespoons, or 15 ounces) of blood will be taken from adults over a 6-week period. A maximum of 7 ml (1/2 tablespoon) of blood per kilogram (2.2. pounds) of body weight will be obtained from children within the same time period, with no more than 3 ml/kg taken at any one time. * Leukapheresis - This procedure is done to collect large quantities of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood is circulated through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm. * Intestinal biopsies - Intestinal tissue will be obtained during colonoscopy with intestinal biopsy in patients who require this procedure as part of their standard medical care. Patients are given a sedative to reduce anxiety, but are conscious during the procedure. A flexible tube is inserted into the rectum and large intestine, allowing the physician to see the intestinal mucosa. At various places, small pieces of tissue are plucked out.

The choice of drug therapy for Crohn's disease depends on several factors, such as the severity of the condition, the sections of the bowel affected, or the patient's previous treatment history. Conventional therapy consists of a short course of corticosteroid treatment followed by azathioprine therapy. Alternatively, there are so-called advanced therapies using biologics (biotechnologically produced protein substances such as antibodies), for example mirikizumab. This study aims to investigate whether direct, early treatment with mirikizumab is more effective than the standard therapy of azathioprine in combination with corticosteroids. Following an inclusion phase, patients will be randomly assigned to either treatment with mirikizumab or azathioprine + corticosteroids. Patients in the azathioprine arm may switch to mirikizumab therapy at three time points from week 24 onwards if they do not respond adequately to azathioprine therapy. The study consists of an initial treatment period of 12 weeks (induction therapy) and a maintenance therapy period of 40 weeks. Patients in the mirikizumab arm receive 13 doses of mirikizumab. This includes initially 900 mg intravenously every 4 weeks followed by 300 mg subcutaneously. In the azathioprine arm patients receive daily administration of azathioprine tablets in combination with a steroid. Assignment to one of the two treatment options is randomised with equal probability for each of the treatment options.