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

Prior treatment

• Treatment with systemic treatment (csDMARDs or bDMARDs or tsDMARDs) and steroid injection in the 6 months previous enrolment.
• Has previously received treatment with an IL-23 inhibitor
• Clinically relevant (chronic or acute) infections, including untreated (latent) tuberculosis, hepatitis B or C or HIV infections;Note: Subjects with a recent acute infection may be enrolled only after full clinical resolution of all signs and symptoms for at least 4 weeks prior to screening.
• Previous or current diagnosis of PsA.

Other illness

• Subjects with a history of cancer within the past 5 years, as well as those with any current or suspected malignancy at the time of enrollment.
• Known hypersensitivity or allergy to Guselkumab or to any component of the investigational medicinal product, including excipients.
• Patients with dementia or an altered mental status, which would preclude the understanding and rendering of informed consent;

Other

• Contraindication to start a new bDMARD treatment course.
• Fulfilment of CASPAR criteria for PsA.
• For women of childbearing potential*: pregnancy status, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3- months after study completion; *A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
• Known immunodeficiency or patients immunocompromised to an extent that participation in the study would pose and unacceptable risk to the patient;
• Presence of swollen joints, dactylitis or at clinical examination.

• Adult ≥ 18 years of age.
• Subject must be able to understand and adhere to all protocol requirements and must voluntarily sign and date an informed consent.
• Subjects are willing and able to comply with procedures required in this protocol.
• Presence of current from moderate to severe skin psoriasis (PASI≥10) or mild psoriasis (PASI≤10) with the involvement of sensitive area (face, palms, soles, nails, and genital area) diagnosed by a dermatologist with experience in the management of psoriatic disease.
• Absence of clinical signs of active arthritis, dactylitis, enthesitis and inflammatory back pain at enrolment.
• Absence of systemic treatment for psoriasis (csDMARDs and/or bDMARDs and/or tsDMARDs treatment) in the last 6 months.
• The presence of peripheral arthralgia clinically suspected for subclinical PsA (definition in Appendix A)
• The Presence of at least 2 out of the following 4 sonographic lesions of subclinical inflammation or structural damage suspicious for a psoriatic musculoskeletal inflammation: (i) articular synovitis GS≥ 2 in at least 2 joints; (ii) tenosynovitis GS≥ 1 in at least 2 sites; (iii) active enthesitis in at least one site; (iv) entheseal erosion in at least one site. Ultrasound findings suggestive of subclinical PsA shall be submitted for centralized assessment and independently reviewed by two readers Sonographic Analysis Protocol  The sonographic examination will preferably be performed on the same day as the clinical assessment; however, a delay of up to 72 hours from the clinical evaluation will be tolerated. The ultrasound assessment will be conducted blinded to the clinical examination and focused in a longitudinal and transverse scan of 42 regions encompassing the following: 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), the 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 the lesions (i.e., synovitis, tenosynovitis, enthesitis, peritenon extensor tendon inflammation and bursitis) and damage lesions (i.e., joint erosions, entheseal erosions, enthesophytes and articular osteoproliferation) will be defined according to the OMERACT and EULAR definitions (Appendix B).