Evaluation of Tofacitinib on Coagulation and Platelet Function in Ulcerative Colitis Patients: A Comparative Study with Golimumab, Infliximab, and Adalimumab

The primary objective of this study is to evaluate the effect of **tofacitinib** on platelet function and coagulation in patients with **ulcerative colitis**. This is clinically relevant as it aims to understand the potential impact of tofacitinib on thromboembolic events, which are a significant concern in the management of ulcerative colitis.

Secondary objectives include:

• Evaluating the in vivo effect of tofacitinib on procoagulant status, including platelet function and coagulation, in patients with ulcerative colitis over time.
• Determining if there is a specific effect of tofacitinib on the hemostasis of ulcerative colitis patients treated with this drug compared to biologic drugs for ulcerative colitis.
• Creating a repository of biological samples (serum, plasma, nucleic acids, RNA, feces, and urine) from a cohort of patients with ulcerative colitis, both before and after treatment with tofacitinib or an anti-TNFα, for use in future complementary studies.

The clinical trial focuses on evaluating the effect of tofacitinib on platelet function and coagulation in patients with **ulcerative colitis**. The study population includes both male and female participants over the age of 18, diagnosed with ulcerative colitis according to the criteria of the European Crohn’s and Colitis Organisation (ECCO). Participants are required to have an indication for treatment with anti-TNFα agents such as infliximab, adalimumab, or golimumab, or tofacitinib, and must be receiving a JAK-inhibitor or anti-TNFα for the first time. Additionally, participants should exhibit endoscopic activity of ulcerative colitis within one month of starting treatment, as indicated by a Mayo endoscopic sub-index of ≥ 2. Women of childbearing age participating in the trial are required to use contraceptive methods with an error rate of less than 1% per year. The sponsor has not provided information regarding the total number of participants in the trial. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to evaluate the effect of **tofacitinib** on platelet function and coagulation in patients with **ulcerative colitis**. This study is a randomized, double-blind, controlled trial involving the administration of tofacitinib and anti-TNFα agents, including **infliximab**, **adalimumab**, and **golimumab**. The trial is expected to last until December 31, 2025, with participant involvement spanning a maximum treatment period of 12 months. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age over 18, a diagnosis of ulcerative colitis, and the indication for treatment with the specified drugs. Follow-up visits will occur at regular intervals to monitor the primary endpoint, which involves assessing platelet activation status in platelet-rich plasma samples. Secondary endpoints include evaluating endoscopic activity and response using the Mayo endoscopic sub-score. The end-of-study visit will conclude the participant's involvement, assessing the overall treatment effect and any adverse events. Participants may be terminated early from the study if they experience significant adverse effects, fail to adhere to the study protocol, or withdraw consent. The trial aims to provide comprehensive data on the safety and efficacy of tofacitinib and its role in thromboembolic events in the context of ulcerative colitis treatment.

The clinical trial involves the administration of several treatments, including both experimental and comparator medications. **GOLIMUMAB** is provided as a solution for injection in a pre-filled pen. It is administered via **subcutaneous injection** with a maximum daily dose of 100 mg. The treatment period for golimumab is up to 12 months. The active substance, golimumab, is a protein of other origin, and the formulation is not specifically for pediatric use.

**TOFACITINIB** is the primary experimental medication in this study. It is administered in tablet form, taken orally, with a maximum daily dose of 10 mg. The treatment duration is also up to 12 months. Tofacitinib is a chemical substance and serves as the main focus of the trial, which aims to evaluate its effect on platelet function and coagulation in patients with **ulcerative colitis**.

**INFLIXIMAB** is used as a comparator treatment in the trial. It is provided as a solution for infusion and is administered via **intravenous infusion**. The maximum dose is 5 mg/kg, with a treatment period extending up to 12 months. Infliximab is a protein of other origin and is not formulated for pediatric use.

**ADALIMUMAB** is another comparator treatment, available as a solution for injection in a pre-filled syringe. It is administered through subcutaneous injection, with a maximum daily dose of 40 mg. The treatment period for adalimumab is also up to 12 months. The active substance, adalimumab, is a structurally diverse substance classified as an immunoglobulin.

Throughout the trial, participant compliance with the dosing schedules is monitored to ensure adherence to the treatment protocols. The study does not involve any orphan drug designations, and all medications are used in their standard adult formulations. No additional non-experimental treatments, such as placebo, are specified in the trial protocol.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves evaluating the **platelet activation status** in patients with ulcerative colitis (UC). This will be conducted ex vivo using platelet-rich plasma (PRP) samples from both active and quiescent UC patients, as well as healthy controls. The samples will be incubated with or without the drug tofacitinib or anti-TNFα agents. In vivo analysis will also be performed on samples from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFα, measuring the rate of platelet aggregation.

Secondary endpoints focus on endoscopic activity and response. Endoscopic activity will be assessed using the Mayo endoscopic sub-score, with activity defined as a score of ≥ 2. An endoscopic response is characterized by a decrease of ≥ 1 point in the Mayo endoscopic sub-score three months after starting treatment. Endoscopic remission is defined as a sub-score of ≤ 1, also evaluated three months post-treatment initiation. These assessments will provide comprehensive insights into the efficacy of the treatment regimen in managing UC symptoms and progression.