Evaluation of Guselkumab on Ultrasound-Confirmed Enthesitis Resolution in bDMARD-Naïve Psoriatic Arthritis Patients

The primary objective of this prospective, multicentre, open-label clinical trial is to assess the effect of **Guselkumab** on the resolution of clinical and ultrasound-confirmed enthesitis in patients with psoriatic arthritis (PsA). Enthesitis is a common and debilitating manifestation in PsA, and its resolution is clinically significant as it can lead to improved patient outcomes and quality of life. The study focuses on bDMARD-naïve patients, providing insights into the efficacy of Guselkumab as a treatment option in this specific patient population.

The clinical trial focuses on evaluating the effect of **Guselkumab** on the resolution of clinical and ultrasound-confirmed enthesitis in patients with **psoriatic arthritis**. The study population comprises adult male and female subjects aged 18 years and older. Participants are required to have a diagnosis of psoriatic arthritis according to the CASPAR criteria and must exhibit SPARCC Enthesitis ≥ 1 at baseline. The trial includes individuals who are biologic disease-modifying antirheumatic drug (bDMARD) naïve and have either experienced failure or adverse reactions to at least one conventional synthetic DMARD (csDMARD) or have an indication to start systemic therapy with Guselkumab due to moderate-to-severe plaque psoriasis. The trial population was selected based on these criteria, and the sponsor has not provided the total number of participants. Both male and female subjects are included, and the study considers vulnerable populations. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **prospective**, multicentre, open-label study designed to evaluate the effect of **guselkumab** on the resolution of ultrasound-proven enthesitis in patients with **psoriatic arthritis** who are biologic disease-modifying antirheumatic drug (bDMARD)-naïve. The trial will involve the administration of **Tremfya**, a 100 mg solution for injection, either in a pre-filled syringe or pen, delivered subcutaneously. The study aims to assess the resolution of clinical and ultrasound-confirmed enthesitis, with the primary endpoint being the resolution of enthesitis (SPARCC = 0) at week 24. The trial is expected to commence recruitment on May 1, 2024, and conclude by December 31, 2027, with a maximum treatment period of 52 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥ 18 years), diagnosis of psoriatic arthritis according to CASPAR criteria, and a history of failure or adverse reaction to at least one conventional synthetic DMARD. The inclusion visit will also ensure that participants have a SPARCC Enthesitis score of ≥ 1 at baseline and meet specific ultrasound criteria. Follow-up visits will be scheduled to monitor the participants' response to treatment and assess the primary endpoint at week 24. The end-of-study visit will occur at the conclusion of the 52-week treatment period or upon early termination.

Participant involvement is expected to last up to 52 weeks, with conditions for early termination including withdrawal of consent, adverse events, or any other medical reasons deemed necessary by the investigator. The trial is categorized as a Phase IV study, indicating it is conducted post-marketing to gather additional information on the drug's effect in a broader patient population. The study is not classified as low intervention, ensuring rigorous monitoring and data collection throughout the trial duration.

The clinical trial involves the administration of **Tremfya**, a pharmaceutical product containing the active substance **guselkumab**. This medication is provided in two forms: a solution for injection in a pre-filled syringe and a solution for injection in a pre-filled pen. Both forms are designed for **subcutaneous** administration. The dosage for each form is 100 mg, with a maximum daily dose of 100 mg and a total maximum dose of 800 mg over the course of the treatment. The treatment period is set to a maximum of 52 weeks. The active substance, guselkumab, is a protein of non-specified origin, and the product is manufactured by Janssen-Cilag International NV. The product is not a paediatric formulation and is not classified as an orphan drug.

The pre-filled syringe form of Tremfya is a solution for injection, specifically designed for ease of administration. The pre-filled pen form offers an alternative method of delivery, also as a solution for injection, providing flexibility in administration based on patient or healthcare provider preference. Both forms are intended to be administered subcutaneously, ensuring that the medication is delivered directly into the tissue beneath the skin for optimal absorption and efficacy. Compliance with the dosing schedule is critical, and participants' adherence to the regimen will be monitored throughout the trial to ensure accurate assessment of the treatment's effects.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this trial. The focus is solely on evaluating the efficacy of guselkumab in resolving ultrasound-proven enthesitis in patients with psoriatic arthritis who are biologic disease-modifying antirheumatic drug (bDMARD)-naïve. The trial aims to provide insights into the therapeutic potential of guselkumab in this patient population, with careful monitoring of dosing schedules and participant compliance to ensure the integrity of the study results.

The efficacy of **Guselkumab** in the treatment of psoriatic arthritis will be assessed in a prospective, multicentre, open-label clinical trial. The primary endpoint for evaluating efficacy is the resolution of enthesitis, as measured by the SPARCC Enthesitis Index, with a target score of SPARCC = 0 at week 24. This endpoint will be used to determine the effect of Guselkumab on the resolution of clinical and ultrasound-confirmed enthesitis in patients who are biologic disease-modifying antirheumatic drug (bDMARD) naïve.

Participants will be evaluated for enthesitis using both clinical assessments and ultrasound imaging. The SPARCC Enthesitis Index will be employed as a validated tool to quantify enthesitis at baseline and at subsequent timepoints, specifically at week 24. The trial is designed to include adult patients diagnosed with psoriatic arthritis according to the CASPAR criteria, who have a SPARCC Enthesitis score of at least 1 at baseline. The trial will also consider patients who have experienced failure or adverse reactions to at least one conventional synthetic DMARD (csDMARD) or have an indication to start systemic therapy with Guselkumab due to moderate-to-severe plaque psoriasis.