Evaluation of Filgotinib on Cardiac Function, Myocardial Inflammation, and Coronary Plaque Morphology in Rheumatoid Arthritis Patients Without Cardiovascular History

The primary objective of this study is to investigate the effect of **Janus kinase inhibitors** on cardiac function, myocardial inflammation, and coronary plaque morphology in patients with **rheumatoid arthritis**. This is clinically relevant as rheumatoid arthritis is associated with increased cardiovascular risk, and understanding the impact of Janus kinase inhibitors could inform treatment strategies to mitigate this risk.

Secondary objectives include assessing differences in cardiac function, myocardial inflammation, and coronary plaque morphology between patients with rheumatoid arthritis and a control group of age- and sex-matched, healthy volunteers. This comparison aims to elucidate the cardiovascular implications of rheumatoid arthritis and the potential modifying effects of Janus kinase inhibitors.

The clinical trial involves participants diagnosed with **rheumatoid arthritis** according to the ACR/EULAR 2010 criteria, specifically excluding those with a history of cardiovascular diseases. The study population comprises both male and female subjects, aged between 40 and 70 years, with moderate to high disease activity as indicated by a Disease Activity Score 28 (DAS28) of 3.2 or higher. Participants must have a clinical indication for treatment with a Janus kinase inhibitor and should not have had any changes to their pharmacological therapy in the last four weeks. 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 effect of **Janus kinase inhibitors** on cardiac function, myocardial inflammation, and coronary plaque morphology in patients with **rheumatoid arthritis**. This study is a randomized, double-blind, controlled trial with an estimated duration from November 2021 to January 2026. Participants will be randomly assigned to receive either the active treatment, **filgotinib** 200 mg film-coated tablets, or a placebo, administered orally. The trial will include a series of study visits to monitor the participants' health and the effects of the treatment.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as a diagnosis of rheumatoid arthritis according to the ACR/EULAR 2010 criteria, moderate to high disease activity, and age between 40 and 70 years. Participants must not have had changes to their pharmacological therapy in the last four weeks. Following the screening, participants will undergo baseline assessments, including cardiac magnetic resonance (CMR) measurements to evaluate left ventricular (LV) function. Subsequent follow-up visits will occur at regular intervals to monitor changes in LV function and other secondary endpoints, such as comparisons with age- and sex-matched healthy volunteers.

The primary endpoint is the change in LV function after one year of treatment, assessed through CMR measurements. Secondary endpoints include comparisons of baseline and follow-up data, with further analysis of clinical treatment evaluation. The expected length of participant involvement is up to 12 months, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial will conclude with an end-of-study visit to perform final assessments and ensure participant safety.

The clinical trial involves the administration of **Jyseleca 200 mg film-coated tablets**, which contain the active substance **filgotinib**. Filgotinib is a chemical compound classified under the ATC code L04AA45. The pharmaceutical form of the medication is a film-coated tablet, designed for oral administration. The dosage regimen for this trial specifies a maximum daily dose of 200 mg, with the total dose not exceeding 200 mg per day. The treatment period is set for a maximum duration of 12 weeks. The tablets are manufactured by ALFASIGMA S.P.A. and are not formulated for pediatric use. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the effects of the experimental medication, Jyseleca, on cardiac function, myocardial inflammation, and coronary plaque morphology in patients with rheumatoid arthritis. Participants' adherence to the medication regimen will be closely monitored to maintain the integrity of the study data.

Efficacy in this clinical trial will be assessed by evaluating the impact of Janus kinase inhibitors, specifically **filgotinib**, on cardiac function in patients with rheumatoid arthritis. The primary endpoint is the change in left ventricular (LV) function after one year of treatment. LV function will be measured using cardiac magnetic resonance (CMR) imaging to assess global circumferential, longitudinal, and radial strain. These measurements will be taken at baseline and at follow-up to determine any changes.

Secondary endpoints include comparisons of baseline and follow-up data in rheumatoid arthritis patients treated with filgotinib for one year, as well as comparisons with age- and sex-matched healthy volunteers. These secondary endpoints are further categorized into those derived from CMR, coronary computed tomography angiography (CCTA), and clinical treatment evaluations. The assessments will be conducted over a one-year period, with the primary and secondary endpoints providing comprehensive data on the efficacy of filgotinib in improving cardiac function and related parameters in the study population.