Plain English Summary
Background and study aims
Psoriatic arthritis (PsA) is a type of inflammatory arthritis that can cause pain and joint damage if left untreated. We have already shown that a ‘Treat to Target’ approach where treatment is increased until a target was achieved for the patients for improved arthritis, psoriasis, quality of life, pain and function. However, there are no studies looking at which drugs work best in this ‘Treat to Target’ approach. The usual strategy is ‘step-up’ approach for all patients, whether they have mild or severe disease. This means at first one standard arthritis drug is used, then two standard drugs together and finally newer stronger biologic drugs for patients not responding to the other drugs. Previous studies in patients with severe disease suggested they may do better if they are treated with stronger drugs earlier. So the aim of this study is to see if patients with moderate to severe PsA do better if they start treatment with two drugs together at the beginning of their treatment or if they start on a biologic drug from the beginning.
Who can participate?
Patients recently diagnosed with moderate to severe PsA who have not previously taken any disease-modifying drugs (DMARDs) for arthritis.
What does the study involve?
Participants are randomly allocated to one of three treatment groups receiving: (1) the standard ‘step-up’ of arthritis drugs – receiving the standard drugs before the stronger biologics; (2) two standard arthritis drugs together; (3) stronger biologic therapy at the start. They have 12 weekly appointments up to 48 weeks which include clinical assessments of their PsA, blood tests and completion of questionnaires.
What are the possible benefits and risks of participating?
The drugs to be used are all current standard treatments for PsA, each with known safety profiles and side effects. The difference for participants is the timing of treatment and therefore the risk of side effects of the treatments received. The potential benefit is an improvement in symptoms and quality of life at an earlier timepoint but this is exploratory as yet.
Where is the study run from?
1. Oxford University Hospitals NHS Foundation Trust
2. Royal United Hospitals Bath NHS Foundation Trust
3. Cambridge University Hospitals NHS Foundation Trust
When is the study starting and how long is it expected to run for?
March 2017 to February 2023
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Laura Coates
Dr Laura Coates
Botnar Research Centre
Nuffield Department of Orthopaedics
Rheumatology & Musculoskeletal Sciences
University of Oxford
+44 (0)1865 737905
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.
To compare the initial effectiveness of early combination DMARD therapy (arm 2) and early use of TNF inhibitors (arm 3) with standard step up care (received in the TWiCs cohort; arm 1).
Approved 01/05/2018, South Central- Oxford B Research Ethic Committee (Whitefriars, Level 3, Block B, Lewin's Mead, Bristol, BS1 2NT, Tel: +44 (0)2071048058, Email: email@example.com), ref: 18/SC/0107
Interventional randomised controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
This is a randomised open-label clinical trial assessing three treatment regimens for PsA:
1. Standard care
2. Early combination DMARD therapy
3. Early biologics (TNF inhibitor) therapy
The trial forms part of a “Trials within Cohorts” or TWiCs design where participants in the cohort may be offered interventional studies subject to meeting the relevant inclusion/exclusion criteria. Consent is requested in the cohort study for data from any control arm to be used without further approach.
A maximum of 315 newly diagnosed patients will be recruited (105 per arm) over a 3 year period. Each participant will be followed for 48 weeks within this trial, all arms will then revert to standard care within the cohort. Participants will attend for study visits at baseline and weeks 12, 24, 36 and 48 in their normal healthcare clinic. At each visit they will be assessed clinically for disease activity, including blood tests, and will be asked to complete patient-reported outcomes questionnaires. Adverse event information will be sought at each visit and recorded, assessed and reported as required by the protocol.
Data will be entered into an electronic CRF and appropriate validation checks carried out. Data will be analysed in accord with a statistical analysis plan starting with the null hypothesis that there is no difference in the proportion of participants achieving a PASDAS good response at week 24 between any of the three treatment arms. If this is significant at the 5% level further analyses will compare each intervention against the control arm.
Primary outcome measure
Response according to PASDAS. This will be reported as the proportion achieving a PASDAS good response (reduction from baseline of ≥1.6 and final score of ≤3.2) in each of the three treatment groups (standard step up therapy in the cohort, early combination DMARD or early TNF inhibitor therapy) at week 24.
Secondary outcome measures
1. Time to achievement of minimal disease activity (MDA), assessed every 12 weeks
2. The proportion of patients achieving a PASDAS good response at week 48; proportion achieving PASDAS moderate response at week 24 and 48
3. Change in PsA impact of disease (PSAID) score from baseline to follow up
4. Proportion achieving PSAID patient acceptable symptom state (≤4) at follow up
5. Change in work productivity (absenteeism, presenteeism and productivity loss) as measured by WPAI at follow up.
6. Cost per QALY in each treatment arm to calculate ICER
7. Clinical assessment, patient questionnaires and blood tests all performed at weeks 0, 24 and 48
8. Healthcare resource use data and health-related quality of life throughout the study
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. Participant is willing and able to give informed consent for participation in the trial.
2. Male or Female, aged 18 years or above.
3. Participants consented to the PsA inception cohort (MONITOR-PsA REC Ref 17/SC/0556) and to be approached for alternate interventional therapies.
4. Poor prognostic factors at baseline. Either:
4.1 Polyarticular disease with > = 5 active joints at baseline assessment OR
4.2 Oligoarticular disease with < 5 active joints at baseline but with one or more of the following poor prognostic factors: raised C reactive protein, radiographic damage, health assessment questionnaire> 1
5. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter (or 2 years if received leflunomide unless treated with washout therapy) as in standard practice.
6. Participant has clinically acceptable laboratory results within 28 days of baseline:
6.1 Haemoglobin count > 8.5 g/dL
6.2 White blood count (WBC) > 3.5 x 109/L
6.3 Absolute neutrophil count (ANC) > 1.5 x 109/L
6.4 Platelet count > 100 x 109/L
6.5 AST or ALT and alkaline phosphatase levels < 3 x upper limit of normal
7. In the Investigator’s opinion, is able and willing to comply with all trial requirements.
8. Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the trial.
Target number of participants
Planned Sample Size: 315; UK Sample Size: 315
Participant exclusion criteria
1. Previous treatment for articular disease with disease modifying drugs (DMARDs) including, but not limited to, methotrexate, sulfasalazine, leflunomide and ciclosporin
2. Female patient who is pregnant, breast-feeding or planning pregnancy during the course of the trial.
3. Significant renal or hepatic impairment.
4. Patients who test positive for Hepatitis B, C or HIV.
5. Contraindication to any of the investigative drugs.
6. Currently abuse drugs or alcohol
7. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
8. Life expectancy of less than 6 months.
9. Any other significant disease or disorder which, in the opinion of the Investigator, may either put patients at risk because of participation in the trial, or may influence the result of the trial, or their ability to participate in the trial.
10. Participation in another research trial involving an investigational product in the past 12 weeks.
11. Additional exclusion criteria apply to patients randomised to arm 3 and receiving adalimumab therapy:
11.1 Active tuberculosis (TB), chronic viral infections, recent serious bacterial infections, those receiving live vaccinations within 3 months of the anticipated first dose of study medication, or those with chronic illnesses that would, in the opinion of the investigator, put the participant at risk.
11.2 Latent TB unless they have received appropriate anti-tuberculous treatment as per local guidelines
11.3 History of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ.
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital Headley Way Headington
Trial participating centre
Royal United Hospitals Bath NHS Foundation Trust
Trial participating centre
Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital Hills Road
University of Oxford
Joint Research Office
NIHR Academy; Grant Codes: CS-2016-16-016
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
1. The researchers intend to publish the methodology of this study in a protocol paper.
2. Peer reviewed scientific journals
3. Conference presentation
4. Publication on website
5. The researchers will also be working with their PPI contributors in case there are any further dissemination routes that should be pursued
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
Participant level data
To be made available at a later date
Basic results (scientific)