Arthritis interception with Guselkumab in subclinical psoriatic arthritis patients in clinical transition from skin to joint disease: a randomized clinical trial.

The primary objective is to determine whether treatment leads to clinical and ultrasonographic improvement in patients with subclinical psoriatic arthritis by Week 24. This is defined as the proportion of patients who achieve resolution of arthralgia, defined as VAS pain ≤ 1/10 and Tender Joint Count (TJC) ≤ 1/10, and/or a measurable and significant improvement in synovio-entheseal inflammation, assessed through the UPsA Activity Score compared with baseline. This objective addresses the critical need to evaluate early intervention strategies in patients transitioning from cutaneous to articular manifestations of psoriatic disease, potentially preventing progression to established psoriatic arthritis.

The secondary objectives include:

• The change of the synovio-entheseal inflammation score detected by ultrasound using a standardized scoring system

• The incidence of progression to psoriatic arthritis, defined as CASPAR criteria fulfillment

• The percentage of patients who achieved clinical resolution of arthralgia, defined as VAS pain ≤ 1/10 and TJC ≤ 1/10

• The percentage of patients who achieve PASI 100

• The change of the Patient Reported Outcomes, including HAQ, BASDAI, DLQI, and PsAID

The trial enrolled a total of **10 participants** diagnosed with **psoriatic arthritis** in clinical transition, specifically individuals with **subclinical psoriatic arthritis**. The study population consisted of **adults aged 18 years and older**, including both **male and female subjects**. Participants were required to have current **moderate to severe skin psoriasis** or **mild psoriasis** affecting sensitive areas such as the face, palms, soles, nails, or genital area, as diagnosed by a dermatologist experienced in psoriatic disease management. All enrolled subjects presented with **peripheral arthralgia** clinically suspected for subclinical psoriatic arthritis but demonstrated no clinical signs of active **arthritis**, **dactylitis**, **enthesitis**, or **inflammatory back pain** at enrollment. A key selection criterion was the presence of at least two specific **sonographic lesions** indicating subclinical inflammation or structural damage, including **articular synovitis**, **tenosynovitis**, **active enthesitis**, or **entheseal erosion**. Participants had not received **systemic treatment** for psoriasis, including conventional synthetic disease-modifying antirheumatic drugs, biologic disease-modifying antirheumatic drugs, or targeted synthetic disease-modifying antirheumatic drugs, within the six months prior to enrollment. The trial included a **vulnerable population**.

This is a Phase 4, open-label, randomized, multicenter clinical trial evaluating the efficacy of **guselkumab** in patients with **subclinical psoriatic arthritis** who are in clinical transition from skin to joint disease. The study will investigate whether treatment leads to clinical and ultrasonographic improvement in patients with subclinical psoriatic arthritis by Week 24. The trial aims to determine the proportion of patients who achieve resolution of **arthralgia**, defined as **VAS pain** ≤ 1/10 and **Tender Joint Count** (TJC) ≤ 1/10, and/or a measurable and significant improvement in synovio-entheseal inflammation assessed through the UPsA Activity Score compared with baseline. The estimated recruitment start date is December 2025, with an estimated end date of December 2027.

Eligible participants must be adults aged 18 years or older with current moderate to severe skin **psoriasis** (**PASI** ≥10) or mild psoriasis (PASI ≤10) with involvement of sensitive areas diagnosed by a dermatologist experienced in psoriatic disease management. Participants must have absence of clinical signs of active arthritis, **dactylitis**, **enthesitis**, and inflammatory back pain at enrollment, and must not have received systemic treatment for psoriasis (csDMARDs, bDMARDs, or tsDMARDs) in the last 6 months. The presence of peripheral arthralgia clinically suspected for subclinical psoriatic arthritis is required, along with at least 2 out of 4 specified **sonographic** lesions of subclinical inflammation or structural damage: articular **synovitis** GS≥2 in at least 2 joints, **tenosynovitis** GS≥1 in at least 2 sites, active enthesitis in at least one site, or **entheseal erosion** in at least one site. Ultrasound findings will be submitted for centralized assessment and independently reviewed by two readers.

The test product is guselkumab, administered as a **subcutaneous injection** in the form of solution for injection in pre-filled syringe at 100 mg/mL concentration. The maximum daily dose is 100 mg, with a maximum total dose of 700 mg over the treatment period. The auxiliary product is **ciclosporin**, administered **orally** as a soft capsule, with a maximum daily dose of 5 mg/kg and a maximum total dose of 1840 mg/kg. Both products have a maximum treatment period of 52 weeks.

The **primary endpoint** is the percentage of patients with subclinical psoriatic arthritis who achieve resolution of arthralgia together with the effect of guselkumab on objectively quantified synovio-entheseal inflammation, evaluated using the UPsA Activity Score at Week 24. Secondary endpoints include the change of synovio-entheseal inflammation score detected by ultrasound at Week 24 and Week 52, the incidence of progression to psoriatic arthritis (defined as **CASPAR criteria** fulfillment) at Week 52, the percentage of patients who achieved clinical resolution of arthralgia at Week 52, the percentage of patients who achieve PASI 100 at Week 24 and Week 52, the change in Patient Reported Outcomes (such as **HAQ**, **BASDAI**, **DLQI**, **PsAID**), and change in total modified Sharp–van der Heijde (mSvH) score from baseline to Week 52, including erosion score and joint space narrowing components.

The sonographic examination will be performed preferably on the same day as the clinical assessment, with a delay of up to 72 hours tolerated. The ultrasound assessment will be conducted blinded to the clinical examination and focused on 42 regions including **metacarpophalangeal**, proximal and distal **interphalangeal joints** of the hands, wrists, knees, **metatarsophalangeal joints**, 12 entheses (Achilles, quadriceps, proximal and distal patellar, plantar aponeurosis and common extensor tendon entheses), 2 retro-calcaneal bursae, and 32 tendons (extensor digitorum tendons of the hands, flexor digitorum tendons of the hands, and extensor tendon compartments of the wrist). The sites to be scanned and sonographic definitions of lesions including synovitis, tenosynovitis, enthesitis, peritenon extensor tendon inflammation, **bursitis**, and damage lesions such as joint erosions, entheseal erosions, **enthesophytes**, and articular osteoproliferation will be defined according to OMERACT and EULAR definitions.

The total duration of participant involvement in the study is 52 weeks. Participants must be able to understand and adhere to all protocol requirements and must voluntarily sign and date an informed consent. Participants are required to be willing and able to comply with procedures required in this protocol throughout the study duration.

The experimental treatment in this clinical trial is guselkumab, administered as a solution for injection in a pre-filled syringe with a concentration of 100 mg/mL. The sponsor product code for this investigational medicinal product is CNTO 1959. Guselkumab is a protein-based active substance classified as Protein - Other in origin. The pharmaceutical form is injection/infusion, administered via subcutaneous injection. The maximum daily dose is 100 mg, with a maximum total dose of 700 mg over the treatment period. The maximum treatment duration is 52 weeks. Guselkumab serves as the test product in this clinical trial investigating the interception of arthritis in patients with subclinical psoriatic arthritis.

Ciclosporin is utilized as an auxiliary medicinal product in this study. The active substance is ciclosporin, which is of chemical origin. The pharmaceutical form is soft capsule, administered via the oral route. The dosing is expressed in mg/kg (milligrams per kilogram), with a maximum daily dose of 5 mg/kg. The maximum total dose is 1840 mg/kg over the course of treatment. The maximum treatment period for ciclosporin is 52 weeks. This product functions as an immunosuppressor and serves a supportive role in the study protocol.

Efficacy will be assessed through co-primary endpoints evaluated at Week 24. The primary efficacy evaluation will measure the percentage of patients with subclinical psoriatic arthritis who achieve resolution of arthralgia, defined as Visual Analogue Scale (VAS) pain ≤ 1/10 and Tender Joint Count (TJC) ≤ 1/10, together with the effect of guselkumab on objectively quantified synovio-entheseal inflammation assessed using the UPsA Activity Score.

Secondary efficacy endpoints include the change in synovio-entheseal inflammation score detected by ultrasound at Week 24 and Week 52, the incidence of progression to psoriatic arthritis defined as CASPAR criteria fulfillment at Week 52, and the percentage of patients who achieved clinical resolution of arthralgia (VAS pain ≤ 1/10 and TJC ≤ 1/10) at Week 52. Additional secondary endpoints comprise the percentage of patients who achieve PASI 100 at Week 24 and Week 52, the change in Patient Reported Outcomes including Health Assessment Questionnaire (HAQ), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Dermatology Life Quality Index (DLQI), and Psoriatic Arthritis Impact of Disease (PsAID), as well as the change in total modified Sharp–van der Heijde (mSvH) score from baseline to Week 52, including erosion score and joint space narrowing components.

Ultrasonographic assessment will be conducted to evaluate subclinical inflammation and structural damage, focusing on 42 regions encompassing metacarpophalangeal, proximal and distal interphalangeal joints of the hands, wrists, knees, metatarsophalangeal joints, 12 entheses, 2 retro-calcaneal bursae, and 32 tendons. The ultrasound examination will be performed blinded to the clinical examination and will assess synovitis, tenosynovitis, enthesitis, peritenon extensor tendon inflammation, bursitis, joint erosions, entheseal erosions, enthesophytes, and articular osteoproliferation according to OMERACT and EULAR definitions. The sonographic examination will preferably be performed on the same day as the clinical assessment, with a tolerated delay of up to 72 hours from the clinical evaluation.