HIPPOCRATES Prospective Observational Study

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease that affects peripheral joints, entheses and axial sites and which complicates skin and/or nail psoriasis in up to 30% of cases[1]. It is estimated that 1-2% of the general population have PsA and so in the EU between 5 to 10 million people have the disease. It is increasingly recognised that PsA is associated with comorbidities, particularly those which promote the development of accelerated atherosclerosis and contribute to cardiovascular morbidity and mortality[2]. While PsA can be classified using a mixture of clinical, laboratory and radiographic features such as in the ClASsification of Psoriatic ARthritis (CASPAR) criteria[3], evidence suggests that the disease develops for several years before sufficient classifiable clinical features emerge. The evolution from psoriasis to the point at which the patient meets the CASPAR criteria for PsA may occur in stages. These stages include: ① patients with skin and/or nail psoriasis only but with risk factors for subsequent development of PsA; ② an immune activation phase when there is evidence of cytokine (e.g. IL-23/IL-17 and/or TNF) over-production at a cellular or tissue level; ③ a stage where there is asymptomatic evidence of synovio-entheseal inflammation on imaging: MRI or ultrasound; ④ a "prodromal stage" where psoriasis patients may have musculoskeletal symptoms such as arthralgia and/or stiffness but without sufficient signs to make a diagnosis of PsA; and ⑤ PsA meeting CASPAR criteria.

There is an important possibility that some of these stages may be reversible. At present, treatment is focused on those patients who receive a PsA diagnosis (stage ⑤ above) and have ongoing inflammatory disease and evidence of radiographic damage. Future treatment intervention needs to focus on earlier stages of disease so as to limit poor long-term outcomes and possibly prevent the development of PsA. Improving our knowledge of the molecular basis of these stages and the transitions between them will enable us to have a deeper understanding of the progression of psoriasis to PsA.

Using a highly cost-effective strategy, this study will recruit a highly cost-effective and patient-driven prospective European observational cohort of 25,000 psoriasis patients to record demographic and clinical features and selectively collect bio-samples (whole blood, 'plasma'). Adults with psoriasis but without a pre-existing diagnosis of PsA will be recruited via clinics, national and international patient support organisations including those under the umbrella of European Federation of Psoriasis Organisations (EUROPSO), and media campaigns.

The cohort will be managed using an ethically approved secure internet-based platform where participants can register using dynamic consent online. The platform already hosts longitudinal capture of patient reported outcomes measures and is implemented across Europe by the rare bone European Reference Network. The platform also allows feedback of study results to participants.

Data collection will be at baseline with updates every 6 months using the online platform. At each follow up timepoint, participants will complete a validated screening questionnaire for PsA and if they screen positive, they will be advised to seek medical review locally. They will also complete participant (patient) reported outcomes studying the burden of psoriasis. All results will be provided as feedback to the participants. At follow up, participants/patients will also be asked to report if they have been diagnosed with PsA and if they have, to confirm this by uploading a scanned copy or photo of their clinic letter with their diagnosis recorded/stated.

Bio-samples will be collected from a sub-set of consenting study participants who have either developed PsA or selected study participants who have been identified to be at low or high risk of PsA (using predictive models developed in other studies). Patient centric bio-sample collection will be achieved using self-administered fingerprick blood sampling kits.

Inclusion criteria

• Adult ≥18 years
• Self-reported diagnosis of skin psoriasis (any form)
• Participant is willing and able to give informed consent for participation in the study and complete data in one of the HPOS languages

Exclusion criteria

• Pre-existing diagnosis of PsA