Effects of Tight-control Strategy With and Without Rosuvastatin on Progression of Subclinical Carotid and Coronary Atherosclerosis in Psoriatic Arthritis- a Randomized Controlled Study

Treatment protocol This is a 1-year prospective, hospital-based, open-label, randomized, controlled trial. The trial comprised two arms. Group 1 will receive T2T strategy together with rosuvastain 20mg daily (T2T-statin group). Group 2 will receive T2T strategy only (T2T-only group). The method of concealed random allocation will be used. Simple randomization will be conducted by a computer-generated random list.

Use of statins The patients will be given the necessary number of rosuvastatin tablets at each visit. At the following visits, surplus medication will be returned to the investigator. Compliance is calculated as a percentage, based on the number of tablets returned.

No trials to date that have evaluated effects on CVD events have tested any medication in combination with statins or treatment to specific LDL-C goals, therefore we do not intensify the regimen for any particular level of LDL-C response. Measuring LDL-C response after initiating therapy in this study is mainly to assess adherence. In this primary prevention trial, in patients who do not tolerate statins, no lipid-lowering therapy will be administered. Potential interventions include lifestyle modification.

Use of DMARDs All participants will receive a 1-year protocolized treatment with the aim to achieve MDA. A predefined treatment protocol is developed based on the EULAR recommendations and the Hong Kong guideline for the use of bDMARDs. Patients fulfilling the criteria for bDMARDs can either pay out of pocket or can apply for the Samaritan Fund for financial assistance, provided they must pass a household-based financial assessment (http://www.ha.org.hk/visitor/ha_visitor_index.asp?content_id=212020). When patient cannot achieve treatment goal within 3-6 months of therapy, the treatment therapy will be escalated to the next step according to the protocol, unless the patient declined or toxic effects preclude this approach. For the introduction of DMARD only joint involvement is taken into account. The participants with active disease who failed non-steroidal anti-inflammatory drug (NSAID) or those with poor prognostic factor will start with methotrexate monotherapy, which is increased to 20mg/week or maximum tolerated dose. Subsequent steps for patients who fail to achieve treatment goal include switching to other conventional synthetic DMARDs (csDMARDs), combination csDMARD therapy or TNFi, ustekinumab, secukinumab or tofacitinib. Intra-articular steroid or local steroid injection to enthesitis and dactylitis are allowed during the study but will be forbidden in the 4 weeks before assessment.

Clinical Assessment Assessment performed at each visit include pain, physicians' and patients' global assessments, number of tender joints count (TJC) and swollen joints count (SJC) (using the 68 tender/66 SJC), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), number of digits with dactylitis; ankylosing spondylitis disease activity score (ASDAS), modified health assessment questionnaire (M-HAQ); Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriasis Area (BSA), Psoriasis Activity and Severity Index (PASI) were used to measure joint and skin disease activity.(31) MDA was used for assessment of treatment efficacy endpoint. The MDA criteria assess 7 domains [TJC ≤ 1, SJC ≤ 1, enthesitis count ≤ 1, skin (≤ 1 or BSA ≤ 3%), function (measured by the Health Assessment Questionnaire), ≤ 0.5, patient's global VAS on a 100-mm scale ≤ 20, and patient pain VAS on a 100 mm scale ≤ 15]. If 5 of 7 of the cutoffs for these domains are met, then the patient is deemed to be in MDA.