Arm 1: Control 'step-up' therapy in the cohort (MONITOR-PsA study). Therapy for the cohort is defined by standard practice in these PsA clinics following current international recommendations\[11\] and National requirements for the prescription of biologic therapy\[19-22\]. Whilst physician discretion is used, most commonly Initial therapy will be with methotrexate alone (15mg/week rising to 25mg/week as tolerated by week 8 of therapy) unless this is contraindicated. In cases of non-response or intolerance to methotrexate, participants will have an alternative DMARD (most commonly sulfasalazine or leflunomide) added or switched to at the discretion of the rheumatologist. In cases of failure of two DMARDs, treatment can be escalated to biologic therapy as per National Institute for Health and Clinical Excellence (NICE) recommendations\[19-22\] usually with a TNF inhibitor as first line. If the requisite disease activity is not met or if there are contraindications to biologics, alternative DMARD combinations will be used. Further details are available in the PsA clinic treatment protocol which is Appendix D in the MONITOR-PsA protocol.

ARM 2: Combination DMARD arm. All participants will be prescribed methotrexate with an additional DMARD (either sulfasalazine or leflunomide) at baseline, staggering the start of these additional therapies by one week to allow more accurate attribution of adverse events. Either sulfasalazine or leflumonide will be used in combination depending on physician preference (taking into account disease presentation, arthritis, enthesitis, skin disease, risk of hypertension and liver disease).Response will be assessed after 12 weeks of therapy using the Minimal Disease Activity (MDA) criteria. These assess 7 different outcomes and patients should meet at least 5 of the 7 items to be classified as being in MDA. Participants who achieve the MDA criteria by week 12 on this combination therapy will continue on this therapy. Participants who show a significant response by in week 12 (a reduction in tender and swollen joint counts of at least 20%) but do not yet meet the MDA criteria should continue on this therapy for an additional 12 weeks before review. Participants failing to show significant response (reduction in joint counts by less than 20%) by week 12 on this combination therapy or those failing to meet MDA criteria by week 24 will be eligible for rescue therapy following the standard PsA clinic treatment protocol (as per arm 1 above and as detailed in the PsA clinic treatment protocol which is found in appendix D of the MONITOR-PsA protocol). Participants may be eligible at this time point for biologic therapy most commonly using TNF inhibitors under NICE guidelines. These state that patients should have failed adequate trials of at least 2 standard DMARDs and that they should have active disease defined as at least 3 tender and 3 swollen joints. If they do not fulfil these NICE criteria (≥3 tender and ≥3 swollen joints) they will be prescribed alternative DMARDs.

ARM 3: Early biologic arm. All participants will be prescribed methotrexate (given weekly) with a TNF inhibitor (adalimumab given every two weeks) at baseline staggering the start of these therapies by one week to allow more accurate attribution of adverse events (TNF inhibitor from week 0, methotrexate from week 1). Treatment with TNF inhibitor will be continued until week 24 at which time the TNF inhibitor will be tapered by spacing out doses which will be received at week 28 and week 32. The TNF inhibitor will be stopped completely after week 32 and participants will continue on methotrexate. In case of flare of disease, participants will be eligible for rescue therapy following the standard PsA clinic treatment protocol (as per arm 1 above and as detailed in the PsA clinic treatment protocol which is found in appendix D of the MONITOR-PsA protocol). According to this protocol they will be started on combination DMARD therapy (sulfasalazine or leflunomide) and may subsequently be eligible for further TNF inhibitor treatment at a later point if they fulfil NICE criteria (as above).

The Investigational Medicinal Products (IMPs) used in this trial are methotrexate, sulfasalazine, leflunomide and adalimumab. All of these medications are used routinely in PsA patients in standard care.