FirST Lines of Biologics in pAtients With ulceRaTivE Colitis: a Randomised Controlled Trial

The goal of treatment is twofold:

* To eliminate or reduce symptoms (this is clinical remission), * To allow the bowel to heal.

When these two goals are achieved, the risk of relapse, hospitalization, surgery, or colorectal cancer decreases.

To monitor the progression of the disease, gastroenterologists use a test called fecal calprotectin: this is a protein measured in stool that helps detect intestinal inflammation.

When conventional treatments like corticosteroids or immunosuppressants are ineffective or poorly tolerated, the investigators use more targeted therapies.

For a long time, doctors have used drugs called anti-TNFs. They block a protein responsible for inflammation (TNF-alpha). These treatments are often injected under the skin, which is generally well-tolerated by patients.

A drug called infliximab, now available as a subcutaneous injection, could be used as a first-line treatment for ulcerative colitis because it appears to be more effective than other injectable anti-TNFs.

Another drug, vedolizumab, works differently from anti-TNFs and can also be used as a first-line treatment.

More recently, new classes of drugs have shown promise:

* JAK inhibitors (such as filgotinib), * interleukin-12 and interleukin-23 inhibitors (such as ustekinumab).

These new treatments have advantages, such as the oral administration method for filgotinib and the fact that they can be used alone, without any other associated medication, which could simplify patients' lives and improve their quality of life.

Today, there are increasingly more different treatments for ulcerative colitis, and the investigators still don't know clearly what the best strategy is:

Is it better to start with one type of medication rather than another? Does the order in which the investigators try treatments lead to different results?

This is an important question for gastroenterologists, as their goal is to choose the most appropriate treatment for each patient from the outset.

The main objective of this research is to compare four strategies, corresponding to four treatment arms, starting with the use of infliximab, filgotinib, vedolizumab, or ustekinumab, to maintain remission in patients with ulcerative colitis.

The following four arms are therefore proposed:

* Based on efficacy: infliximab - filgotinib - ustekinumab - vedolizumab * Based on safety: ustekinumab - vedolizumab - infliximab - filgotinib * Based on current practice: vedolizumab - infliximab - filgotinib - ustekinumab * Based on convenience and route of administration: filgotinib - ustekinumab - vedolizumab - infliximab

This study will also allow for a comparison of the efficacy, safety, participant acceptability, and quality of life of the four treatment regimens.

This study is intended for adult patients (aged 18 to 65), male or female, with moderate or severe ulcerative colitis (UC) for at least 3 months. Treatment for these patients must require biologic therapy, as determined by the investigator. Participants must be able to provide informed consent to participate in the research and must be covered by a national health insurance plan. Women of childbearing age must be using active contraception for at least the duration of the study (2 years).

Patients will be followed for two years. They will be seen at the initial visit, then every two months during the first year, and then every three months during the second year. At each visit, they will be required to undergo blood and stool tests and complete a questionnaire. Endoscopies will be scheduled for weeks 16, 52, and 104. Patient treatments can be optimized once, and based on the endoscopic score, patients may change treatments according to a predefined sequence.