SPEED
Research type
Research Study
Full title
Clinical effectiveness of standard step up care (methotrexate) compared to early combination DMARD therapy with standard step up care compared to early use of TNF inhibitors with standard step up care for the treatment of moderate to severe psoriatic arthritis: a 3-arm parallel group randomised controlled trial.
IRAS ID
236590
Contact name
Laura Coates
Contact email
Sponsor organisation
University of Oxford
Eudract number
2017-004542-24
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Psoriatic Arthritis (PsA) is an inflammatory arthritis estimated to occur in 15% of people with psoriasis, affecting around 150,000 people in the UK. Two-thirds of people with PsA suffer progressive joint damage with associated disability. PsA is associated with a reduced life expectancy related to the risk of comorbidities.
Recent International treatment recommendations utilise an approach to treatment of regular review and ‘step-up’ of treatment as appropriate. However they suggest more intensive therapy for those with poor prognostic factors (number of active joints, systemic inflammatory levels, baseline radiographic damage and poor function). Combinations of disease-modifying anti-rheumatic drugs (DMARDs), usually methotrexate with a second DMARD, have been shown to have some advantages over single therapies in PsA. Early use of tumour necrosis factor (TNF) inhibitors has also been shown to be superior to methotrexate in a head to head open label trial but there is no data on long term outcomes. Applying initial intensive therapy including early biologics has shown improved outcomes in other inflammatory arthritides such as RA but has never been tried in PsA. In patients with established PsA receiving TNF inhibitors, ultrasound levels of disease activity have been shown to predict the chance of disease flare. Inclusion of US prior to dose reduction of the TNF inhibitor will allow assessment of this as a predictor of successful withdrawal.
This is a three arm open label RCT within a TWiCs design (Trials Within Cohort; Monitor-PsA REC Ref 17/SC/0556). Participants will be randomised 1:1:1 to receive, over 48 weeks, standard therapy or initial combination DMARD therapy or initial TNF inhibitor therapy. The aim is to establish in a full RCT whether initial intensive therapy with either combination DMARDs or early biologics is superior to a step up treatment approach in moderate/severe PsA. Patients will be recruited who have one of the recognized poor prognostic markers i.e. they will have to have polyarticular disease (≥5 active joints) or to have oligoarthritis (<5 active joints) but with other poor prognostic factors (raised C reactive protein, poor function, radiographic evidence of erosions).REC name
South Central - Oxford B Research Ethics Committee
REC reference
18/SC/0107
Date of REC Opinion
1 May 2018
REC opinion
Further Information Favourable Opinion