Comparison of Vedolizumab, Filgotinib, Ustekinumab, and Infliximab as First-Line Advanced Therapy to Maintain Remission in Patients with Ulcerative Colitis

The primary objective of this study is to compare different therapeutic strategies as first-line advanced therapy to maintain remission in patients with ulcerative colitis. The comparison involves the use of anti-integrins, JAK inhibitors, anti-IL12/23, and anti-TNF agents (Scope: 3).

The secondary objectives include:

• Evaluation of efficacy at 12 and 24 months, including assessments of first-line, second-line, third-line, and fourth-line therapies, as well as the impact of therapeutic intensification.
• Assessment of safety profiles and the identification of predictors for venous thromboembolism.
• Comparison of patient-reported outcomes, specifically acceptability, quality of life, and levels of disability.
• Identification of predictive factors for treatment response or failure through a multi-omics approach, encompassing proteomics, metagenomics, metabolomics, transcriptomics, genetics, epigenetics, and immunophenotyping.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with ulcerative colitis for a minimum of three months. Eligible participants are aged between 18 and 65 years and present with moderate to severe disease, defined by a modified Mayo score of 5 to 9 and an endoscopic Mayo score of 2 or greater. Inclusion requires an inadequate response, failure, loss of response, or intolerance to 5-aminosalicylic acid, corticosteroids, or immunosuppressants. Women of childbearing age must use effective contraception and demonstrate a negative pregnancy test.

This randomized controlled trial is designed to compare different first-line advanced therapy strategies for the maintenance of remission in patients with ulcerative colitis. The study evaluates four therapeutic approaches: anti-integrins (vedolizumab), JAK inhibitors (filgotinib), anti-IL12/23 (ustekinumab), or anti-TNF agents (infliximab). The research methodology utilizes an open-label design to assess efficacy and safety over time. Following a screening visit to confirm eligibility based on diagnosis, modified Mayo score, and previous treatment response, participants are assigned to a treatment group. The clinical assessment of the primary endpoint, which involves composite remission criteria including bowel habit normalization and faecal calprotectin levels, occurs monthly between week 4 and week 52. Subsequent follow-up visits are conducted at various intervals, including weeks 16, 24, 32, 42, 52, 76, and 104, to monitor endoscopic improvement, histological healing, and clinical remission. The total duration of participant involvement extends up to 104 weeks. Early termination may occur based on study protocols or safety considerations.

The clinical trial evaluates several therapeutic strategies for the maintenance of remission in patients with ulcerative colitis. The experimental treatments include different classes of advanced therapy.

Ustekinumab is administered as a solution for infusion, provided as STEQEYMA 130 mg concentrate. The dosage is 22.5 mg via intravenous infusion.

Infliximab is administered as a solution for infusion, provided as Remsima 100 mg powder for concentrate. The dosage is 17.40 mg via intravenous infusion.

Filgotinib is administered as a film-coated tablet, provided as Jyseleca 200 mg. The dosage is 45 mg via oral administration.

Vedolizumab is administered as a solution for infusion, provided as Entyvio 300 mg powder for concentrate. The dosage is 15.40 mg via intravenous infusion.

The efficacy of the therapeutic strategies for ulcerative colitis will be evaluated using a primary endpoint of remission, defined by composite criteria including the absence of rectal bleeding, normalization of bowel habits (Mayo sub-score of stool frequency = 0), faecal calprotectin levels < 150 µg/g, and no use of steroids. This binary criterion will be assessed monthly between week 4 and week 52.

Secondary endpoints include:

• Remission within the first 24 months and absence of symptoms within the first 12 or 24 months.
• Biological remission based on faecal calprotectin levels (< 50 µg/g, < 150 µg/g, or < 250 µg/g).
• Endoscopic improvement (Mayo endoscopic score ≤ 1), endoscopic remission (Mayo endoscopic score = 0), and clinical remission (total Mayo score ≤ 2 without any subscore > 1) at week 16, week 52, and week 104.
• Endoscopic remission based on the Modified Mayo Score involving stool frequency subscore ≤ 1, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1 at week 16, week 52, and week 104.
• Histological healing (Nancy index ≤ 1) and histo-endoscopical mucosal improvement or healing at week 16, week 52, and week 104.
• Symptomatic remission and faecal calprotectin levels assessed at each visit.
• Clinical remission rates, time to drug failure, and time to clinical response regarding rectal bleeding, bowel habits, and urgency.
• Acceptability of drug regimen via a numerical scale, colectomy rate, and adverse events at week 8, week 16, week 24, week 32, week 42, week 52, week 76, and week 104.
• Partial Mayo score and simple clinical colitis activity index at week 8, week 16, week 24, week 32, week 42, week 52, week 76, and week 104.
• Quality of life using the IBD questionnaire and disability via the IBD disability index at week 8, week 16, week 24, week 32, week 42, week 52, week 76, and week 104.
• Disappearance of faecal urgency, rectal bleeding, and normalization of bowel habits at scheduled intervals from week 8 to week 104.