A study of pre-clinical joint disease in psoriasis and the imaging response to ustekinumab

INTERVENTION: Participants are randomised to: Methotrexate ‐ the current first‐line standard tablet treatment for moderate to severe psoriasis Ustekinumab (IMP) ? anti‐IL12/23 p40 monoclonal antibody CONDITION: Psoriatic disease (psoriasis and psoriatic arthritis) ; Skin and Connective Tissue Diseases ; Psoriasis PRIMARY OUTCOME: To assess the change in subclinical enthesitis from baseline in patients with psoriasis treated for 24 weeks with ustekinumab for their skin disease INCLUSION CRITERIA: 1. Male and female patients aged 18‐80 years 2. Diagnosis of plaque psoriasis (dermatologist confirmed) 3. Duration of psoriasis greater than twelve months 4. Moderate or severe disease [Psoriasis Area and Severity Index (PASI score >10)] 5. No prior treatment with systemic or biologic agents 6. No current or prior symptoms of psoriatic arthritis (or arthralgia/ articular symptoms) 7. Evidence on screening ultrasound of subclinical enthesitis (GUESS score >12) 8. All male and female subjects biologically capable of having children must agree to use at least one reliable method of contraception for the duration of the study and for 24 weeks after the end of the study. Acceptable methods of contraception are surgical sterilization, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives SECONDARY OUTCOME: 1. To assess the feasibility of a full randomized controlled trial (RCT) comparing ustekinumab with first line systemic therapies for the management of subclinical psoriatic joint disease in patients with moderate or severe psoriasis.; 2. To estimate the baseline prevalence of peripheral subclinical enthesitis in systemic and biologic treatment‐naïve patients with plaque psoriasis, recruited from a new‐patient psoriasis clinic, with a PASI score greater than 10 and no symptoms of joint disease (as assessed by the CASPAR criteria) at presentation. ; 3. To estimate the baseline prevalence of subclinical axial arthropathy in systemic and biologic treatment‐naïve patients with plaque psoriasis, recruited from a new‐patient psoriasis clinic, with a PASI score greater than 10 and no symptoms of joint disease (as assessed by the CASPAR criteria) at presentation. ; 4. To assess the change in subclinical peripheral and axial inflammatory joint disease from baseline in patients with psoriasis treated for 24 weeks with ustekinumab for their skin disease; 5. To establish if a relationship exists between the change from baseline in any routine clinical scoring measures and the change in subclinical enthesopathy on ultrasound after treatment with ustekinumab:; 5.1. Skin disease severity: PASI score; 5.2. Skin disease extent: BSA measurement (expressed as a percentage); 5.3. Psychosocial impact: DLQI score; 5.4. Nail disease severity: NAPSI score; 6. To evaluate whether there is an association between the pattern of plaque psoriasis (e.g. scalp disease) in systemic and biologic naïve patients and the severity of subclinical enthesopathy before treatment.; 7. To validate the utility of optical coherence tomography in the assessment of subclinical nail disease in patients with psoriasis, compared to ultrasound, in terms of:; 7.1. Efficacy/level of detection of abnormalities; 7.2. Variability/Reproducibility; 8. To investigate the prevalence and severity of the OCT changes seen in subclinical psoriatic nail disease in patients with moderate or severe psoriasis (PASI >10) prior to treatment with systemic and biologic therapies.; 9. To evaluate whether there is an association between the severity of subclinical psoriatic nail disease and the severity of subclinical joint disease in patients with moderate or severe psoriasis (PASI >10) who are systemic and biologic‐treatment naïve. ; 10. To assess the change in subclinical psoriatic nail disease from baseline in patients with psoriasis treated for 24 weeks with ustekinumab for their skin disease (open label).; 11. To investigate which, if any, serological abnormalities exist in our psoriasis cohort (particularly in relation to the metabolic system and cardiovascular risk) and to quantify the change in these biomarkers from baseline after 24 weeks of treatment with ustekinumab.