Evaluation of Adalimumab, Vedolizumab, and Tofacitinib on Aortic Stiffness and Cardiovascular Risk in Ulcerative Colitis Patients

The primary objective of this study is to compare the **carotid intima-media thickness (CIMT)** after 3 months of therapy in patients with **ulcerative colitis** treated with anti-TNF agents, vedolizumab, and tofacitinib. This is clinically relevant as CIMT is a recognized marker of atherosclerosis and cardiovascular risk, and understanding its modulation by these therapies could inform treatment strategies for reducing cardiovascular complications in ulcerative colitis patients.

Secondary objectives include:

• Comparing arterial stiffness after 3 months of therapy in ulcerative colitis patients treated with anti-TNF, vedolizumab, and tofacitinib.
• Comparing CIMT and arterial stiffness after 12 months of therapy, and their evolution, in patients treated with these agents.
• Comparing biomarkers of endothelial dysfunction and coagulation parameters at baseline, 3 months, and 12 months, in responders and non-responders to the treatments.
• Comparing coagulation parameters at baseline, 3 months, and 12 months, in responders and non-responders to biologics.
• Comparing levels of neutrophil extracellular traps (NETs) at baseline, 3 months, and 12 months, in responders and non-responders.
• Comparing the Framingham score, 10-year atherosclerotic cardiovascular disease (ASCVD) risk indices, and SCORE at baseline, 3 months, and 12 months, in responders and non-responders to ulcerative colitis therapy.
• Comparing lipid levels at baseline, 3 months, and 12 months, in responders and non-responders to ulcerative colitis therapy.

The clinical trial involves participants diagnosed with **ulcerative colitis**, a condition that must have been present for at least six months. The study population includes both male and female subjects, all of whom are over the age of 18. Participants are required to be initiating treatment with infliximab, adalimumab, golimumab, vedolizumab, or tofacitinib. All participants must be covered by French national health insurance and have provided written informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the impact of **anti-TNF**, **vedolizumab**, and **tofacitinib** on aortic stiffness, carotid intima-media thickness (CIMT), and cardiovascular risk in patients with **ulcerative colitis**. This study is a randomized, double-blind, controlled trial with an estimated duration from June 2021 to June 2026. Participants will be randomly assigned to receive one of the investigational medicinal products, which include AMGEVITA, XELJANZ, Entyvio, Inflectra, or Simponi, each administered according to its approved route and dosage. The trial will assess the primary endpoint of CIMT after three months of therapy, alongside secondary endpoints such as aortic pulse wave velocity, augmentation index, and various cardiovascular risk scores.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are confirmed, including a diagnosis of ulcerative colitis for at least six months, age over 18 years, and initiation of treatment with one of the specified medications. Participants must also be covered by French national health insurance and provide written informed consent. Follow-up visits will occur at regular intervals to monitor treatment effects and collect data on primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, with a comprehensive assessment of all collected data.

Participant involvement is expected to last up to 16 months, depending on the specific treatment regimen. Conditions that may lead to early termination from the study include adverse reactions to the investigational products, withdrawal of consent, or any significant protocol deviations. The trial is categorized as low intervention, as the investigational products are used in accordance with their marketing authorizations. This study aims to provide valuable insights into the cardiovascular implications of these treatments in ulcerative colitis patients.

The clinical trial involves the administration of several experimental medications to evaluate their impact on cardiovascular risk factors in patients with **ulcerative colitis**. The first experimental medication is **AMGEVITA**, which contains the active substance **adalimumab**. It is provided as a 40 mg solution for injection in a pre-filled syringe. The pharmaceutical form is a solution for injection, and it is administered intravenously. The maximum daily dose is 40 mg, with a total maximum dose of 2080 mg over a treatment period of 12 months. Participant compliance is monitored through regular assessments of dosing schedules and administration records.

Another experimental medication used in the trial is **XELJANZ**, containing the active substance **tofacitinib**. This medication is available as 5 mg film-coated tablets and is administered orally. The maximum daily dose is 20 mg, with a total maximum dose of 2240 mg over a treatment period of 16 weeks. Compliance is ensured by tracking the oral administration and adherence to the prescribed dosing schedule.

**Entyvio** is also included in the study, with the active substance **vedolizumab**. It is provided as a 300 mg powder for concentrate for solution for infusion. The pharmaceutical form is a solution for infusion, administered intravenously. The maximum daily dose is 300 mg, with a total maximum dose of 3600 mg over a 12-month treatment period. Administration is monitored to ensure proper infusion techniques and adherence to the dosing schedule.

**Inflectra**, containing the active substance **infliximab**, is another medication used in the trial. It is available as a 100 mg powder for concentrate for solution for infusion. The pharmaceutical form is a solution for infusion, administered intravenously. The maximum daily dose is 5 mg/kg, with a total maximum dose of 5 mg/kg over a 12-month treatment period. Compliance is monitored through infusion records and participant follow-up.

Lastly, **Simponi**, with the active substance **golimumab**, is administered as a 45 mg/0.45 mL solution for injection in a pre-filled pen. The pharmaceutical form is a solution for injection, administered intravenously. The maximum daily dose is 40 mg, with a total maximum dose of 1400 mg over a 12-month treatment period. Participant compliance is tracked through injection records and adherence to the prescribed dosing regimen.

The efficacy of the clinical trial will be assessed by evaluating the impact of anti-TNF, vedolizumab, and tofacitinib on cardiovascular parameters in patients with **ulcerative colitis**. The primary endpoint for efficacy assessment is the measurement of carotid intima-media thickness (CIMT) after three months of therapy. Secondary endpoints include aortic pulse wave velocity (aPWV) for arterial stiffness, augmentation index (AIx), Framingham score, 10-year atherosclerotic cardiovascular disease risk indices (ASCVD), SCORE score, ulcerative colitis activity score (Mayo Score), lipid parameters (HDL, LDL, TC, TG), arterial tension and systolic pressure index, and endothelial function/coagulation parameters.

These parameters will be measured and collected at specified timepoints throughout the trial. The trial is designed to compare these cardiovascular and disease activity parameters in patients treated with infliximab, adalimumab, golimumab, vedolizumab, or tofacitinib. The trial will follow a structured schedule to ensure consistent data collection and analysis, adhering to validated scales and laboratory tests where applicable. The trial is expected to conclude by June 2026, with recruitment having started in June 2021.