Conditions: Psoriatic Arthritis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1
Healthy volunteers: no

Brief summary:
POISE is a two arm interventional trial nested within a cohort (Trials Within Cohorts or TWiCs design). This tests less aggressive early therapy in patients newly diagnosed with low impact oligoarticular PsA. Arm 1 will receive standard step up therapy in the cohort and act as the control group. Arm 2 will receive local steroid injections to active joints and will be able to use non-steroidal anti-inflammatory drugs (NSAIDs) only

Detailed description:
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 and National requirements for the prescription of biologic therapy. 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 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: Symptomatic therapy arm. The intervention will delay standard treatment with disease-modifying anti-rheumatic drugs (DMARDs) and use local glucocorticoid injections to affected joints instead. Oral non-steroidal anti-inflammatory drugs (NSAIDs) will also be allowed as concomitant medication as indicated for individuals. Local glucocorticoid injections will include injections with methylprednisolone or triamcinolone. All active joints will be treated with glucocorticoid injections. Glucocorticoid injections can be either be given as an intra-articular injection to an inflamed joint or as an intra-muscular injection if multiple joints are involved. If any joint requires more than 2 local injections of glucocorticoid within a 6 month period, then the patient is deemed to have failed symptomatic therapy and will be withdrawn from the treatment protocol and be treated as per usual care (in most cases with DMARD therapy). If Participants require DMARD therapy, they will be offered rescue therapy as per usual clinical care but will be asked to continue with data collection for the trial. This is to ensure that sufficient data is collected for the trial but risks in delaying treatment to the individual are mitigated.

Arms:
arm 1: Control 'step-up' therapy in the cohort (MONITOR-PsA study). Therapy for the cohort is defined by standard NHS practice. Commonly Initial therapy will be with methotrexate alone unless this is contraindicated. In cases of non-response or intolerance to methotrexate, participants will have an alternative DMARD (sulfasalazine or leflunomide). 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. If the requisite disease activity is not met or if there are contraindications to biologics, alternative DMARD combinations will be used. arm 2: Symptomatic therapy arm. The intervention will delay standard treatment with disease-modifying anti-rheumatic drugs (DMARDs) and use local injections of methylprednisolone or triamcinolone to affected joints instead. Oral non-steroidal anti-inflammatory drugs (NSAIDs) will also be allowed as concomitant medication. All active joints will be treated with injections. Injections can be either be given as an intra-articular injection or as an intra-muscular injection. If any joint requires more than 2 local injections of glucocorticoid within a 6 month period, then the patient is deemed to have failed symptomatic therapy and will be withdrawn from the treatment protocol and be treated as per usual care (in most cases with DMARD therapy).

Interventions: intervention 1: Methotrexate intervention 2: Sulfasalazine intervention 3: Leflunomide intervention 4: Methylprednisolone intervention 5: Triamcinolone
Intervention descriptions: intervention 1: Methotrexate up to 25mg/week as tolerated po or sc intervention 2: Sulfasalazine up to 3g daily po intervention 3: Leflunomide 10-20mg daily po intervention 4: For IA or IM injection 20-120mg intervention 5: For IA or IM injection 20-120mg

Protocol document:
Prot_SAP_000.pdf: 
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Derived from Clinical Trial Protocol Template version 12.0 © Copyright: The University of Oxford and 
Oxford University Hospitals NHS Foundation Trust 2016 
Trial Title:  Clinical effectiveness of symptomatic therapy compared to standard step up care for the 
treatment of low impact psoriatic oligoarthritis: a 2 arm parallel group feasibility study 
/ Short title: POISE - Psoriatic Oligoarthritis Intervention with Symptomatic thErapy 
Ethics Ref: 18/SC/0261 
EudraCT Number: 2018-001085-42 Date and Version No: 27Aug2019 V6.0 
 
Chief Investigator:
Dr Laura Coates
Nuffield 
Department 
of 
Orthopaedics, 
Rheumatology 
and 
Musculoskeletal Sciences, University of Oxford 
Principal Investigators: 
Dr William Tillett, Royal United Hospital, Bath, UK
Dr Deepak Jadon, University of Cambridge Hospitals NHSFT, Cambridge, 
UK 
Dr Nicola Gullick, Rheumatology, University Hospital, Clifford Bridge 
Road, Coventry, UK  
Ben Thompson, Newcastle, The Newcastle upon Tyne Hospitals NHS 
Foundation Trust , Freeman Hospital, Newcastle upon Tyne , UK 
Sponsor: 
University of Oxford  
Clinical Trials and Research Governance, Boundary Brook House, 
Churchill Drive, Headington, OXON, OX3 7LQ 
Email: ctrg@admin.ox.ac.uk  
Funder: 
National Institute for Health Research CS-2016-16-016
Chief Investigator Signature: 
 
Statistician Signature: 
 
 
Please declare any/no potential conflicts of interest. 
Laura Coates – none 
 
William Tillett – none  
Deepak Jadon – none 
Nicola Gullick - none 
Ben Thompson - none 


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Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, Health Research Authority (HRA), host organisation, and members of the 
Research Ethics Committee (REC), unless authorised to do so. 
TABLE OF CONTENTS 
 
1. 
KEY TRIAL CONTACTS ............................................................................................................................. 5 
2. 
SYNOPSIS ............................................................................................................................................... 6 
3. 
ABBREVIATIONS ..................................................................................................................................... 7 
4. 
BACKGROUND AND RATIONALE .......................................................................................................... 10 
4.1. 
Proposed interventions ............................................................................................................... 11 
Methylprednisolone acetate BP (such as Depo-Medrone®) ............................................................... 12 
Triamcinolone (such as Kenalog®) ....................................................................................................... 12 
5. 
OBJECTIVES AND OUTCOME MEASURES ............................................................................................. 12 
6. 
TRIAL DESIGN ....................................................................................................................................... 14 
7. 
PARTICIPANT IDENTIFICATION ............................................................................................................ 14 
7.1. 
Trial Participants .......................................................................................................................... 14 
7.2. 
Inclusion Criteria .......................................................................................................................... 14 
7.3. 
Exclusion Criteria ......................................................................................................................... 15 
8. 
TRIAL PROCEDURES ............................................................................................................................. 16 
8.1. 
Screening and Eligibility Assessment ........................................................................................... 16 
8.2. 
Recruitment ................................................................................................................................. 16 
8.3. 
Informed Consent ........................................................................................................................ 17 
8.4. 
Randomisation, blinding and code-breaking ............................................................................... 17 
8.5. 
Baseline Assessments .................................................................................................................. 18 
8.6. 
Subsequent Visits ........................................................................................................................ 19 
8.7. 
Sample Handling .......................................................................................................................... 20 
8.8. 
Discontinuation/Withdrawal of Participants from Trial Treatment ............................................ 20 
8.9. 
Discontinuation/Withdrawal of a site ......................................................................................... 21 
8.10. 
Definition of End of Trial.......................................................................................................... 21 
9. 
INVESTIGATIONAL MEDICINAL PRODUCT (IMP) ................................................................................. 21 
9.1. 
IMP Description ........................................................................................................................... 21 


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Methylprednisolone acetate BP .......................................................................................................... 21 
Triamcinolone ...................................................................................................................................... 22 
9.2. 
Storage of IMP ............................................................................................................................. 22 
9.3. 
Compliance with Trial Treatment ................................................................................................ 22 
9.4. 
Accountability of the Trial Treatment ......................................................................................... 22 
9.5. 
Concomitant Medication ............................................................................................................. 22 
9.6. 
Post-trial Treatment .................................................................................................................... 23 
10. 
SAFETY REPORTING ......................................................................................................................... 23 
10.1. 
Definitions ............................................................................................................................... 23 
10.2. 
Causality .................................................................................................................................. 24 
10.3. 
Procedures for Recording Adverse Events .............................................................................. 24 
10.4. 
Reporting Procedures for Serious Adverse Events .................................................................. 25 
10.5. 
Expectedness ........................................................................................................................... 25 
10.6. 
SUSAR Reporting ..................................................................................................................... 25 
10.7. 
Development Safety Update Reports ...................................................................................... 25 
11. 
STATISTICS ....................................................................................................................................... 26 
11.1. 
Description of Statistical Methods .......................................................................................... 26 
11.2. 
Health Economics analysis....................................................................................................... 26 
11.3. 
The Level of Statistical Significance ......................................................................................... 27 
11.4. 
Criteria for the Termination of the Trial .................................................................................. 27 
11.5. 
Procedure for Accounting for Missing, Unused, and Spurious Data. ...................................... 27 
11.6. 
Inclusion in Analysis ................................................................................................................. 27 
11.7. 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan ........................ 27 
12. 
DATA MANAGEMENT ...................................................................................................................... 27 
12.1. 
Source Data ............................................................................................................................. 27 
12.2. 
Access to Data ......................................................................................................................... 28 
12.3. 
Data Recording and Record Keeping ....................................................................................... 28 
13. 
ORGANISATION ............................................................................................................................... 29 
13.1. 
Project timetable and milestones ........................................................................................... 29 
13.2. 
Trial Steering Committee ......................................................................................................... 29 
13.3. 
Trial Management Group ........................................................................................................ 29 
13.4. 
Data Safety and Monitoring Committee ................................................................................. 29 
13.5. 
Local Co-ordination ................................................................................................................. 30 
14. 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 30 


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15. 
SERIOUS BREACHES ......................................................................................................................... 30 
16. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................... 31 
16.1. 
Declaration of Helsinki............................................................................................................. 31 
16.2. 
Guidelines for Good Clinical Practice ...................................................................................... 31 
16.3. 
Approvals ................................................................................................................................. 31 
16.4. 
Reporting ................................................................................................................................. 31 
16.5. 
Participant Confidentiality ....................................................................................................... 31 
16.6. 
Expenses and Benefits ............................................................................................................. 31 
16.7. 
Other Ethical Considerations ................................................................................................... 32 
17. 
FINANCE AND INSURANCE .............................................................................................................. 32 
17.1. 
Funding .................................................................................................................................... 32 
17.2. 
Insurance ................................................................................................................................. 32 
18. 
PUBLICATION POLICY ....................................................................................................................... 32 
19. 
REFERENCES .................................................................................................................................... 32 
20. 
APPENDIX A:  RECRUITMENT AND INCLUSION TO TRIAL ................................................................ 34 
21. 
APPENDIX B:  TRIAL FLOW CHART ................................................................................................... 36 
22. 
APPENDIX C:  SCHEDULE OF PROCEDURES ..................................................................................... 37 
23. 
APPENDIX D:  SAE REPORTING FLOW CHART .................................................................................. 39 
24. 
APPENDIX E:  AMENDMENT HISTORY ............................................................................................. 40 
 
 
 


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1. KEY TRIAL CONTACTS 
Chief Investigator
Dr Laura Coates
Nuffield 
Department 
of 
Orthopaedics, 
Rheumatology 
and 
Musculoskeletal Sciences, University of Oxford 
Botnar Research Centre, Windmill Road, Oxford, OX3 7LD 
Tel 01865 737838 
Laura.coates@ndorms.ox.ac.uk  
Sponsor
Ms Heather House
Boundary Brook House, Churchill Drive, Headington, OXON, OX3 7LQ 
Email: ctrg@admin.ox.ac.uk  
Trial 
Management 
Office 
Monitor 
PsA 
Study, 
Nuffield 
Department 
of 
Orthopaedics, 
Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, 
Windmill Road, Oxford, UK, OX3 7LD.  
Email: monitorpsa@ndorms.ox.ac.uk  
Clinical Trials Unit
OCTRU Nuffield Department of Orthopaedics, Rheumatology and 
Musculoskeletal Sciences, Botnar Research Centre, Windmill Road, 
Oxford, UK, OX3 7LD. 
Tel: 01865 223469 ; Email: octrutrialshub@ndorms.ox.ac.uk  
Statistician(s)
Ines Rombach, Medical Statistician
Susan Dutton, Medical Statistician 
OCTRU/Center for Statistics in Medicine, Nuffield Department of 
Orthopaedics, Rheumatology and Musculoskeletal Sciences, University 
of Oxford 
Botnar Research Centre, Windmill Road, Oxford, OX3 7LD 
Ines.rombach@ndorms.ox.ac.uk 
Susan.dutton@ndorms.ox.ac.uk  
Trial Steering 
Committee 
 
Chair – Dr Philip Helliwell, Research Rheumatologist, Leeds Institute of 
Rheumatic and Musculoskeletal Medicine, University of Leeds, 
email:p.helliwell@leeds.ac.uk 
 
Data Safety and 
Monitoring Committee 
Chair – Dr Jon Packham, Consultant Rheumatologist, Staffordshire and 
Stoke 
on 
Trent 
Partnership 
NHS 
Trust, 
Stoke 
on 
Trent. 
Jon.Packham@ssotp.nhs.uk 
 
 
 
 


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2. SYNOPSIS 
 
Trial Title
Clinical effectiveness of symptomatic therapy compared to standard step up 
care for the treatment of low impact psoriatic oligoarthritis:a 2 arm parallel 
group feasibility study. 
Short title
POISE - Psoriatic Oligoarthritis Intervention with Symptomatic thErapy
 
Trial Design
Feasibility study within Trials Within Cohorts (TWiCs) design
Trial Participants
Participants from the MONITOR-PsA cohort with mild psoriatic arthritis 
Planned Sample Size
60, 30 to the cohort as controls and 30 receiving the intervention
Sites
1) Nuffield Orthopaedic Centre, Windmill Rd, Headington, Oxford OX3 7HE. 
Tel: 0300 304 7777 
2) Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, 
Bath, BA1 1RL. Tel: 01225 465941 
3) Addenbrooke’s Hospital, Hills Rd, Cambridge CB2 0QQ. Tel: 01223 
245151 
4) Coventry Rheumatology, University Hospital, Clifford Bridge Road, 
Coventry CV2 2DX, Tel: 024 7696 6705 
5) Newcastle, The Newcastle upon Tyne Hospitals NHS Foundation Trust , 
Freeman Hospital, Newcastle upon Tyne, NE7 7DN. Tel: 0191 233 6161  
Treatment duration
48 weeks
Follow up duration
48 weeks
Planned Trial Period
16thJuly 2018 to 16thJuly 2021
Objectives
Outcome Measures
Primary
 
To determine the feasibility of 
conducting a future definitive 
trial to establish whether a 
subgroup of Participants with 
mild psoriatic arthritis (PsA) can 
be 
safely 
and 
effectively 
managed 
without 
disease-
modifying anti-rheumatic drugs 
(DMARDs).   
 
To 
establish 
the 
acceptability 
of 
conservative management in mild PsA 
and the feasibility of a future definitive 
trial the study will assess  
 
1. The proportion of eligible  
Participants in the cohort over 
the recruitment period for 
POISE 
2. The proportion of Participants  
consenting to the study which 
will indicate that they find the 
intervention acceptable 
3. The proportion of  Participants 
not offered DMARD therapy 
during the 48 week trial period 
(DMARD therapy will be offered 
if Participants have active 
disease despite 2 doses of 
glucocorticoids to the same 


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joint within a 6 month period as 
stated in section 4) 
 
Secondary
 
To develop the design of a future 
definitive 
trial 
to 
establish 
whether 
a 
subgroup 
of 
Participants with mild PsA can be 
safely and effectively managed 
without DMARDs.   
 
The primary outcome of the future study 
will be the proportion of Participants 
achieving 
a 
good 
response 
level 
(reduction from baseline of >1.6 and 
final score of <3.2) in the PsA Disease 
Activity Score (PASDAS)[2].   Descriptive 
data on PASDAS will be collected to 
allow accurate sample size estimations 
for any future trial. 
Exploratory objectives
 
To evaluate exploratory 
outcome measures that may be 
used to generate hypotheses for 
future studies. They may be 
required in later studies on the 
cohort as part of the TWiCs 
approach 
 
They may be required in later 
studies on the cohort as part of 
the TWiCs approach. ACR20, 50 
and 70[23] 
 
Safety (AEs, ADRs and SAEs reported 
during the trial period) 
 
Treatment satisfaction measured by 
the treatment satisfaction 
questionnaire for medication 
(TSQM)[26] 
 
The feasibility of conducting an 
economic evaluation of the delayed 
DMARD therapy group will be 
assessed.  An assessment will be 
made on the best way to express 
cost-effectiveness and most 
appropriate sources of unit cost 
data for potential resource 
consequences. 
 
Investigational 
Medicinal Products with 
Formulation, 
Dose, 
Route of Administration 
Glucocorticoids:
 
Methylprednisolone acetate BP 10-40mg to be given as intra-articular 
injection or 80-120mg to be given as intra-muscular injection as detailed 
in section 9.1 
 
Triamcinolone 10-40mg to be given as intra-articular injection or 80-
120mg to be given as intra-muscular injection as detailed in section 9.1 
 
3. ABBREVIATIONS 
ACPA 
Anti citrullinated peptide antibody 
ACR 
American College of Rheumatology 
ADR 
Adverse Drug Reaction (i.e. ARs and SARS) 
AE 
Adverse event 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
AR  
Adverse reaction 
BASDAI 
Bath ankylosing spondylitis disease activity index 


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BASFI 
The Bath Ankylosing Spondylitis Functional Index 
BASMI 
Bath ankylosing spondylitis metrology index 
BSA 
Body surface area 
CASPAR 
ClASsification criteria for Psoriatic Arthritis 
CI 
Chief Investigator 
CRF/eCRF 
Case Report Form/electronic Case Report Form 
CRP 
C-reactive protein 
CTRG 
Clinical Trials and Research Governance 
DMARD 
Disease-modifying anti-rheumatic drugs 
DMSC 
Data Monitoring and Safety Committee 
DSUR 
Development Safety Update Report 
eGRF 
estimated glomerular filtration rate test 
EMS 
Early Morning Stiffness 
EULAR 
European League Against Rheumatism 
EuroQol 
European Quality of Life 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
GRAPPA 
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 
HAQ 
Health Assessment Questionnaire 
HRQol 
Health-related quality of life 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
IL12/23/17 
Interleukin 
IMP 
Investigational Medicinal Product 
LEF 
Leflunomide 
MHRA 
Medicines and Healthcare products Regulatory Agency 
NSAID 
Non-steroidal anti-inflammatory drugs 
NHS 
National Health Service 
NRES 
National Research Ethics Service  
OCTRU 
Oxford Clinical Trials Research Unit 
PARS 
PsA Ratingen Score 
PASDAS 
Psoriatic arthritis disease activity score 
PASI 
Psoriasis area and severity index 
PI 
Principal Investigator 


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PIS 
Participant/ Patient Information Sheet 
PsA 
Psoriatic Arthritis 
PROMS 
Patient Reported Outcome Measures 
PSAID 
Psoriatic Arthritis Impact of Disease 
RCT 
Randomised Controlled Trial 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
RF 
Rheumatoid factor 
RNHRD 
Royal National Hospital for Rheumatic Diseases 
SAP 
Statistical Analysis Plan 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
 SJC  
 Swollen joint count 
SmPC 
Summary of Medicinal Product Characteristics 
SOP 
Standard Operating Procedure 
SPARCC 
Spondyloarthritis Research Consortium of Canada 
SSZ 
Sulfasalazine 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TJC 
Tender joint count 
TSC 
Trial Steering Committee 
TMF 
Trial Master File 
TMG 
Trial Management Group 
TNF 
Tumour necrosis factor 
TSC 
Trial Steering Committee  
TSQM 
Treatment satisfaction questionnaire for medication 
TWiCs 
Trials within Cohorts 
US 
Ultrasound 
VAS 
Visual Analogue Scale 
WBC 
White Blood Count 
WPAI 
Work productivity and activity impairment 
 
 
 


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4. BACKGROUND AND RATIONALE 
Psoriatic Arthritis (PsA) is an inflammatory arthritis estimated to occur in 15% of people with psoriasis[3] 
affecting around 150,000 people in the UK[4].  Audit data from Oxford in 2015 shows that 21.5% of patients 
in the early arthritis clinic have PsA.  Two-thirds of people with PsA suffer progressive joint damage with 
associated disability[5, 6].  People with PsA have similar functional and quality of life impairment to 
rheumatoid arthritis[7].  PsA is associated with a reduced life expectancy[8] related to the risk of 
comorbidities, particularly the metabolic syndrome[9].  Direct costs to healthcare are estimated at £2,400 
per patient annually with indirect costs (time lost from work and activities) per patient of over £8,000[10].  
PsA is a highly heterogenous disease[11] with a proportion of patients having mild non-progressive 
disease[12].  Well validated prognostic factors in PsA can identify these patients including number of active 
joints, systemic inflammation levels, radiographic damage and functional ability at presentation[13-15].  
There is little research addressing outcomes and treatment options for mild disease[16-18].  It is likely that 
some patients are over treated with conventional ‘step up’ therapy leading to unnecessary side effects for 
the patient and costs to the healthcare system.  A previous study in undifferentiated peripheral 
spondyloarthritis found that 55% of Participants did not require disease-modifying anti-rheumatic drugs 
(DMARDs) and could be managed with only intra-articular steroid injections and analgesia.  However, only 
4 of 59 Participants had a diagnosis of PsA [16].  In established disease ultrasound (US) inflammation in the 
joints predicts future flare of disease in those already on treatment[19]. 
This trial will investigate the feasibility and acceptability of the study design to establish whether 
Participants with mild PsA can be managed without DMARDs.  Participants with newly diagnosed PsA will 
be eligible if they fulfil the following criteria: 
1. Oligoarthritis (<5 joints involved) 
2.  No poor prognostic markers 
Baseline US may identify a sub-group of Participants for whom conservative treatment is most beneficial.  
This data will enable me to design and power a definitive trial of delayed DMARD treatment for mild PsA. 
The intervention will delay standard treatment with disease-modifying anti-rheumatic drugs (DMARDs) 
and use local steroid injections to affected joints instead.  Oral non-steroidal anti-inflammatory drugs 
(NSAIDs) will also be allowed as concomitant medication as indicated for individuals.  Local steroid 
injections will include injections with methylprednisolone or triamcinolone. 
Potential risks include side effects from NSAIDs, side effects from steroid administration or side effects 
from the intra-articular administration.  All of these will be detailed in the patient information sheet.  In 
case of requirement of more than 2 local injections to any specific joint within a 6 month timeframe,  
Participants will be withdrawn from the treatment protocol and be treated as per usual care (in most cases 
with disease-modifying anti-rheumatic drugs (DMARD) therapy).   This is to ensure that risks in delaying 
treatment are mitigated. 
This trial is nested within a cohort (MONITOR-PsA) forming the basis of a Trials Within Cohorts (TWiCs) 
design.  This method recruits a central cohort having “treatment as usual” with regular observations and 
then adds pragmatic trials of alternative therapies where a random group of eligible Participants are 
selected.  This allows robust generalizability from studies to routine health care, avoids attrition and 
disappointment bias from controls in open label studies as  Participants only receive information relevant 
to their care, aids recruitment to trials, allows routine collection of long term outcomes and increases 


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efficiency with multiple trials within one cohort[20]. This will allow us to address outcomes with a 
pragmatic ‘treat to target’ approach in a real-life cohort and compare other therapeutic interventions.  
This design is particularly suited to open label trials with “treatment as usual” as the comparator.  It is ideal 
for chronic conditions, situations where multiple trials may be performed and where expensive desirable 
treatments are being trialed[20].  Thus Participants in this POISE study will be recruited from and followed 
as part of the MONITOR cohort. 
4.1. Proposed interventions 
A schema of the proposed interventions is shown in appendix B. 
All Participants will be randomized into either arm 1 or 2 of the POISE trial and those randomized to the 
offer of an intervention will also be asked to have a baseline ultrasound (US) scan of key joints and entheses 
to establish the degree of any subclinical inflammation.  Baseline ultrasound scoring of disease activity is 
included as an exploratory outcome.  A baseline ultrasound of 44 joints and 10 entheses will be performed 
as the optimal sites for US in PsA are not yet established.  This allows calculation of the PsA sonographic 
(PsASon) scoring system[21]. 
ARM 1: Control ‘step-up’ therapy in cohort (MONITOR-PsA Cohort study REC REF 17/SC/0556). Therapy 
for the cohort is defined by standard NHS practice in these PsA clinics following current international 
recommendations[22] and National requirements for the prescription of biologic therapy[4, 23-25].  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 (SSZ) or leflunomide (LEF)) added or switched to at the discretion of the rheumatologist.  In 
cases of failure of two disease-modifying anti-rheumatic drugs (DMARDs), treatment can be escalated to 
biologic therapy as per National Institute for Health and Clinical Excellence (NICE) recommendations[4, 23-
25] usually with a tumour necrosis factor (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 Cohort 
protocol. 
ARM 2: Symptomatic therapy arm.  The intervention will delay standard treatment with disease-modifying 
anti-rheumatic drugs (DMARDs) and use local glucocorticoid injections to affected joints instead.  Oral non-
steroidal anti-inflammatory drugs (NSAIDs) will also be allowed as concomitant medication as indicated 
for individuals.  Local glucocorticoid injections will include injections with methylprednisolone or 
triamcinolone.   Participants will be reviewed at weeks 12, 24, 36 and 48 routinely.  They will also have a 
trial helpline contact so that if their disease flares between these visits they can contact the team to be 
reviewed at an extra visit in between these.  All active joints will be treated with glucocorticoid injections.  
Glucocorticoid injections can be either be given as an intra-articular injection to an inflamed joint or as an 
intra-muscular injection if multiple joints are involved.  The choice of glucocorticoid will be left to the 
treating physician depending on the joint involved and local routine practice.  If any joint requires more 
than 2 local injections of glucocorticoid within a 6 month period, then the patient is deemed to have failed 
symptomatic therapy and will be withdrawn from the treatment protocol and be treated as per usual care 
(in most cases with DMARD therapy).   If Participants require DMARD therapy, they will be offered rescue 
therapy as per usual clinical care but will be asked to continue with data collection for the trial. This is to 
ensure that sufficient data is collected for the trial but risks in delaying treatment to the individual are 
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Methylprednisolone acetate BP (such as Depo-Medrone®) 
This will be supplied as a sterile aqueous suspension in vials containing 40 mg methylprednisolone acetate, 
macrogol, sodium chloride, myristyl-gamma-picolinium chloride and sterile water for injections. 
This drug will be used for local injections given as intra-articular injections to inflamed joints or local 
injections to active enthesitis around tendon insertions.  In the case of multiple active joints, an 
intramuscular injection of methylprednisolone acetate can be used instead of intra-articular injections.  
Each vial of methylprednisolone acetate will be used as supplied. Doses of between 10 and 120mg of 
methylprednisolone will be used according to the table below: 
Joint
Dose
Small joint/enthesis e.g. fingers
10-20 mg
Medium joint/enthesis e.g. wrist
20-40 mg
Large joint e.g. knee
40-80 mg
Intramuscular injection
80-120 mg
Details of how these will be used are given further in section 4.1 on interventions. 
Triamcinolone (such as Kenalog®) 
This will be supplied as a sterile aqueous suspension in vials containing 40mg triamcinolone, benzyl alcohol, 
polysorbate 80m sodium carboxymethylcellulose, sodium chloride and sterile water for injections. 
This drug will be used for local injections given as intra-articular injections to inflamed joints or local 
injections to active enthesitis around tendon insertions.  In the case of multiple active joints, an 
intramuscular injection of triamcinolone can be used instead of intra-articular injections.  Each vial of 
triamcinolone will be used as supplied.  Doses of between 10 and 80mg of triamcinolone will be used 
according to the table below: 
Joint
Dose
Small joint/enthesis e.g. fingers
10-20 mg
Medium joint/enthesis e.g. wrist
20-40 mg
Large joint e.g. knee
40 mg
Intramuscular injection
80-120 mg
Details of how these will be used are given further in section 4.1 on interventions. 
5. OBJECTIVES AND OUTCOME MEASURES 
Objectives
Outcome Measures
Timepoint(s) of evaluation of 
this 
outcome 
measure 
(if 
applicable) 
Primary Objective
To determine the feasibility of 
conducting 
of 
a 
future 
definitive trial to establish 
whether 
a 
subgroup 
of 
Participants with mild PsA can 
To establish the acceptability of 
conservative management in mild 
PsA and the feasibility of a future 
definitive trial the study will assess  
1 & 2: Baseline assessment in 
MONITOR-PsA cohort  
3: follow-up at 48 weeks 


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be 
safely 
and 
effectively 
managed without DMARDs.   
 
1. The proportion of eligible 
Participants in the cohort 
over the recruitment 
period for POISE 
2. The proportion of 
Participants  consenting to 
the study which will 
indicate that they find the 
intervention acceptable 
3. the proportion of  
Participants not offered 
DMARD therapy during the 
48 week trial period 
(DMARD therapy will be 
offered if Participants have 
active disease despite 2 
doses of glucocorticoids to 
the same joint within a 6 
month period, as in section 
Secondary Objectives
To develop the design of a 
future 
definitive 
trial 
to 
establish whether a subgroup 
of Participants with mild PsA 
can be safely and effectively 
managed without DMARDs.   
 
The primary outcome of the future 
study will be the proportion of 
Participants 
achieving 
a 
good 
response level (reduction from 
baseline of ≥1.6 and final score of 
≤3.2[1]) in the PsA Disease Activity 
Score (PASDAS)[2].   Descriptive 
data on PASDAS will be collected to 
allow 
accurate 
sample 
size 
estimations for any future trial. 
 All 
follow-up 
visits 
where 
measured - as detailed in 
Appendix 
C 
schedule 
of 
procedures. 
Baseline US assessment will be 
related to future requirement of 
DMARD therapy to consider if 
baseline US should be stratified for 
in the randomisation of a future 
trial.   
US of joints and entheses at 
baseline 
Exploratory objectives
To evaluate exploratory 
outcome measures that may 
be used to generate 
hypotheses for future studies. 
They may be required in later 
 
ACR20, 50 and 70[23] 
 
Safety (AEs, ADRs and SAEs 
reported during the trial period)
 
Treatment satisfaction 
measured by the treatment 
All 
follow-up 
visits 
where 
measured - as detailed in 
Appendix 
C 
schedule 
of 
procedures.  


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studies on the cohort as part 
of the TWiCs approach 
 
satisfaction questionnaire for 
medication (TSQM)[26] 
The feasibility of conducting an 
economic evaluation of the 
delayed DMARD therapy group will 
be assessed.  An assessment will be 
made on the best way to express 
cost-effectiveness and most 
appropriate sources of unit cost 
data for potential resource 
consequences. 
 
 
6. TRIAL DESIGN 
A flowchart of the study is shown in Appendix A. 
This is a randomised open-label feasibility trial assessing the acceptability of conservative management in 
mild PsA and the feasibility of a future definitive trial within a cohort in a “Trials within Cohorts” or TWiCs 
design.  A maximum of 60 Participants will be recruited (30 to the cohort, arm 1 as controls and 30, arm 2 
receiving the intervention). The number is an estimate, as at present we do not know how many 
Participants with mild disease will be eligible and willing to participate. It is estimated that around 15% of 
Participants referred with new PsA may be eligible.  Each participant will be followed for 48 weeks within 
this trial and will then revert to standard care within the cohort. 
 Participants in this study will attend for study visits at baseline and weeks 12, 24, 36 and 48.   Participants 
in the intervention arm will also be able to attend for joint injections as required in between these visits 
via a trial helpline.  At all visits, Participants will be assessed clinically for disease activity and will be asked 
to complete patient reported outcomes via questionnaires. 
Data collected from all Participants will be entered within the cohort study (MONITOR-PsA) data recording 
systems. The data consists of clinical assessments, patient reported questionnaires and documentation of 
routine efficacy and safety blood tests. These assessments are detailed in section 8. 
7. PARTICIPANT IDENTIFICATION 
7.1. Trial Participants 
This trial will recruit adult Participants from MONITOR-PsA with newly diagnosed PsA who have not 
previously received treatment with DMARDs for their articular disease.  For this trial, only Participants with 
mild disease defined as low disease activity and impact will be eligible (see below). 
7.2. Inclusion Criteria 


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 
 Participants consented to the PsA inception cohort (MONITOR-PsA) and to be approached for 
alternate interventional therapies. 
 
 Participants with mild disease as defined by: 
 
Oligoarticular disease with <5 active joints at baseline assessment.Participant is willing and able to 
give informed consent for participation in the trial. 
 
Male or female. 
 
Aged 18 years or above. 
 
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 (defined as 
true abstinence, oral contraceptives, implants, intrauterine device, barrier method with spermicide, 
or surgical sterilization)  during the trial and for 3 months thereafter  (or 2 years if received leflunomide 
unless treated with washout therapy) as in standard practice. 
 
Participant has clinically acceptable laboratory results within 6 weeks of enrolment: 
o Haemoglobin count > 8.5 g/dL 
o White blood count (WBC) > 3.5 x 109/L 
o Absolute neutrophil count (ANC) > 1.5 x 109/L 
o Platelet count > 100 x 109/L 
o ALT and alkaline phosphatase levels <3 x upper limit of normal 
o eGFR 
 
 
In the Investigator’s opinion, is able and willing to comply with all trial requirements. 
 
Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the 
trial. 
7.3. Exclusion Criteria 
The patient may not enter the trial if ANY of the following apply: 
 
≥1 poor prognostic factors for psoriatic arthritis, from 
o raised C reactive protein (CRP) defined as > 4g/dl for standard non-hsCRP 
o radiographic damage defined as the presence of ≥ 1 erosion on plain radiographs of the 
hands and feet 
o health assessment questionnaire (HAQ) score > 1 
 
Contraindications to non-steroidal anti-inflammatory drugs 
 
Previous treatment for articular disease with synthetic DMARDs (including methotrexate, 
leflunomide or sulfasalazine) or biologic DMARDs (including TNF, IL12/23 or IL17 inhibitor 
therapies) or targeted synthetic DMARDs (PDE4 of JAK inhibitor therapies). 


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 
Female patient who is pregnant, breast feeding or planning pregnancy during the course of the 
trial. 
 
Significant renal or hepatic impairment. 
 
Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. 
 
Any other significant disease or disorder which, in the opinion of the Investigator, may either put 
the patients at risk because of participation in the trial, or may influence the result of the trial, or 
the participant’s ability to participate in the trial. 
 
Patients who have participated in another research trial involving an investigational product in the 
past 12 weeks. 
 
8. TRIAL PROCEDURES 
A flowchart for recruitment and inclusion in this TWiCs cohort is shown in appendix B.  
8.1. Screening and Eligibility Assessment 
Potential Participants will be identified from the MONITOR-PsA cohort which is recruited from new 
referrals to the rheumatology service particularly those referred to the early arthritis clinic. Participants 
will be identified and approached initially by their reviewing/treating clinical care team and will be given 
brief information about the cohort.  If they are interested, a Participant Information Sheet and consent 
form will be given to them and explained.  If they are happy to consent to the observational study, then 
this can be performed on the same day.  However as stated in 8.2, they will be allowed as much time as 
they wish to consider their participation. 
As part of the consent process for the MONITOR-PsA Cohort Participants will be asked to consent to the 
following items as part of the Trials Within Cohorts design.  
1. To be contacted by the research team about future interventional studies 
2. To be randomised by the research team for an invitation to participate in these future 
interventional studies 
3. For anonymized data to be used as comparison as a control group for these future interventional 
studies. 
If they consent to the cohort and also consent to be contacted about future interventional studies, then 
their baseline data will be reviewed to see if they fulfil the inclusion/exclusion criteria for this study.  If 
they are potentially eligible and have consented to be randomised to an invitation to participate in further 
interventional studies then they will be randomised either to remain in the cohort as a control subject or 
to be offered one of the two interventions.  If they are randomised to be offered an intervention, further 
information will be given as detailed below in section 8.2 and appropriate time will be given for the 
participant to consider the invitation and discuss participation with friends/family. 
8.2. Recruitment 
If Participants are randomised to be offered the intervention then they will be approached initially by their 
reviewing/treating clinical care team within the cohort study and will be given brief information about the 


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intervention.  If they are interested they will be given the full patient information sheet (PIS) and informed 
consent form (ICF) for this trial as well as a verbal explanation of the trial.  They will be allowed as much 
time as they wish to consider their participation as stated in 8.3.  If they decline to consent then they will 
be followed only in the cohort (in line with their previous cohort consent). If they are happy to consent to 
the intervention, then they will be asked to sign the consent form prior to any study related procedures 
occurring.  
8.3. Informed Consent 
The participant must personally sign and date the latest approved version of the Informed Consent form 
before any trial specific procedures are performed. 
Written and verbal versions of the PIS and ICF will be presented to the Participants detailing no less than: 
the exact nature of the trial; what it will involve for the participant; the implications and constraints of the 
protocol; the known side effects and any risks involved in taking part. It will be clearly stated that the 
participant is free to withdraw from the trial at any time for any reason without prejudice to future care, 
without affecting their legal rights and with no obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will participate 
in the trial. Written Informed Consent will then be obtained by means of participant dated signature and 
dated signature of the person who presented and obtained the Informed Consent. The person who 
obtained the consent must be suitably qualified and experienced, and have been authorised to do so by 
the Chief/Principal Investigator (CI/PI). A copy of the completed ICF will be retained by the Participants 
and one will be retained in the healthcare record. The original will be retained at the sites. 
The PIS will outline that the Participants name and contact details (including mobile, phone and email), 
will be collected to facilitate follow up and full data collection. A copy will sent to the study coordinating 
team in Oxford using secure encrypted electronic transfer.  These details may be used by the study team 
to check contact details using the NHS Digital and other central UK NHS bodies, and to provide other basic 
study-related information that may be needed for follow up and to allow possible telephone contact if 
they do not attend clinic visits.  The ICF will also ask for permission to allow access to participant data by 
responsible members of the University of Oxford or the NHS Trust for monitoring and/or audit of the study 
to ensure we are complying with regulations. 
8.4. Randomisation, blinding and code-breaking 
As described in section 8.1, randomisation will be carried out if Participants have indicated a willingness 
to be contacted about and randomised into additional interventional trials and if they meet the 
inclusion/exclusion criteria based on the baseline cohort data collection.   
Randomisation to the interventions will be undertaken via a centralised randomisation service run through 
the Oxford Clinical Trials Research Unit (OCTRU). Computer-generated randomisation allocations using a 
minimisation approach including a random element will ensure balanced allocations across the treatment 
groups.  The following minimisation factors will be used: 
 
Recruiting trial site 
 
Duration of disease prior to diagnosis (<12 months, ≥12 months) 
The randomisation schedule will be designed by the statistician from OCTRU and will be held within the 
database system.   


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The treatment received is open-label so there is no necessity for code breaking. 
A member of the research team will undertake disease activity assessments blinded. 
8.5. Baseline Assessments 
Baseline assessments must be performed before Participants start on treatment. The intervention will 
delay standard treatment with DMARDS and use local glucocorticoid injections to affected joints if and 
when required. See Appendix C ‘Schedule of procedures’ for the time points of when the corticosteroids 
are dispensed. The following will be assessed for all Participants within the cohort study (MONITOR-PsA) 
so this data will already be available: 
 
Medical history 
 
Medication (glucocorticoids and non-steroidal anti-inflammatory drugs only) 
 
Physical examination: pulse; blood pressure; height; weight 
 
Safety bloods: haemoglobin, WBC, platelet count, neutrophils, ALT.  
 
Antibody markers: anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) 
 
*Efficacy bloods: CRP and eGFR 
 
PsA history: PsA type; symptom onset; diagnosis date; peripheral and axial early morning 
stiffness (EMS); inflammatory axial pain. 
 
Classification Criteria for Psoriatic Arthritis (CASPAR) Criteria:  
o Evidence of current psoriasis  
o Personal history of psoriasis  
o Family history of psoriasis nail dystrophy including onycholysis, pitting, and 
hyperkeratosis  
o Evidence of current or documented history of dactylitis 
o Personal history or dactylitis 
o Rheumatoid factor negative 
o Evidence of new bone formation on radiographs. 
 
Full clinical disease assessment:  
o *TJC and SJC: a full 68 tender and 66 swollen joint count will be performed. Replaced 
joints will not be counted 
o *Dactylitis Assessment using count of tender dactylitic digits  
o *Enthesitis Assessment using Leeds[27] and Spondyloarthritis Research Consortium of 
Canada (SPARCC)[28] enthesitis index 
o Psoriasis Area Severity Index (PASI)  and body surface area (BSA) 
o *Physician’s visual analogue scale (VAS) of overall disease activity 
o  (BASMI) (only if clinical/imaging evidence of axial involvement) 
 
Copies of radiographs will be saved for the modified Sharp-van der Heijde radiographic score for 
PsA [29] and PsA Ratingen Score (PARS) [30].  
Specific to this study protocol, patients will be randomized into either arm 1 or 2 of the POISE trial  and 
those randomized to the offer of an intervention will also be asked to have a baseline ultrasound (US) scan 
of key joints and entheses to establish the degree of any subclinical inflammation.  Baseline ultrasound 
scoring of disease activity is included as an exploratory outcome.  A baseline ultrasound of 44 joints and 
10 entheses will be performed as the optimal sites for US in PsA are not yet established.  This allows 
calculation of the PsA sonographic (PsASon) scoring system[21]. 


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Participants will be asked to complete the following patient reported outcomes: 
 
*Global disease activity visual analogue scale (VAS) 
 
Patient pain VAS 
 
Health assessment questionnaire (HAQ)[31] 
 
PsA impact of disease (PSAID)[32] 
 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
 
*SF36[33] 
 
EQ-5D-5L[34] 
 
Work productivity and activity impairment (WPAI)[35] 
 
BASFI 
 
The primary outcome of a future proposed trial would be the proportion of Participants maintaining low 
disease activity as measured by the PASDAS (≤3.2) at week 48.  The PASDAS is a composite score including 
both clinical assessment and patient reported outcomes.  It is calculated as (((0.18√physician global VAS) 
+ (0.159√patient global VAS) – (0.253 x √SF36-PCS) + (0.101 x LN (SJC+1)) + (0.048 x LN (TJC+1)) + (0.23 x 
LN (Leeds enthesitis index +1)) + (0.37 LN (tender dactylitis count+1)) + (0.102 x LN (CRP+1)) +2) x 1.5.  The 
items in the PASDAS are marked above in the list of outcomes with an asterisk.  Descriptive data on the 
PASDAS will be collected in this feasibility study to allow for estimation of appropriate sample size for a 
future definitive trial. 
8.6. Subsequent Visits 
Follow up will be for 48 weeks with data to be collected at 12, 24, 36 and 48 weeks for this trial. Local 
glucocorticoid injections will include injections with methylprednisolone or triamcinolone. See Appendix 
C ‘Schedule of procedures’ for the time points of when the corticosteroids are dispensed in the case of 
active arthritis requiring treatment. Participants receiving the intervention will also be able to contact the 
trials team via a helpline if they require steroid injections in between these visits. All active joints will be 
treated with glucocorticoid injections which are either given as an intra-articular to an inflamed joint or as 
an intra-muscular injection if multiple joints are involved.  
At each visit the following assessments will be performed in line with the cohort study: 
 
Medical history (update) 
 
Current treatment for psoriatic arthritis  
 
Concomitant medication history (glucocorticoids and non-steroidal anti-inflammatory drugs 
only) 
 
Treatment tolerability 
 
Physical examination: pulse; blood pressure; weight 
 
Safety bloods: haemoglobin, WBC, platelet count, neutrophils, ALT.  
 
Efficacy bloods: CRP and eGFR 
 
Full clinical disease assessment:  
o TJC and SJC: a full 68 tender and 66 swollen joint count will be performed. Replaced 
joints will not be counted 
o Dactylitis Assessment using count of tender dactylitic digits  
o Enthesitis Assessment using Leeds[27] and (SPARCC)[28] enthesitis index 
o  (PASI)  (BSA) 


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o Physician’s VAS of overall disease activity 
Participants will be asked to complete the following patient reported outcomes: 
 
Global disease activity visual analogue scale (VAS) 
 
Patient pain VAS 
 
Health assessment questionnaire (HAQ)[31] 
 
PsA impact of disease (PSAID)[32] 
 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
 
SF36[33] 
 
Work productivity and activity impairment (WPAI)[35] 
 
Health system utilisation data 
 
Treatment satisfaction measured by the treatment satisfaction questionnaire for medication 
(TSQM)[26] 
 
BASFI 
 
Compliance with treatment 
At certain visits additional assessments will be performed: 
 
Week 24 and 48 
o EQ-5D-5L[34] 
o Health system utilisation data 
 
Week 48 
o Copies of radiographs will be saved for the modified Sharp-van der Heijde radiographic 
score for PsA [29] and PsA Ratingen Score (PARS) [30]. 
At baseline and 48 weeks 
o (BASMI) (only if clinical/imaging evidence of axial involvement) 
 
8.7. Sample Handling 
Routine safety and efficacy blood tests will be performed for all Participants receiving disease-modifying 
therapy as done in standard NHS care.  The results of the routine NHS blood tests will be recorded to 
monitor safety of the treatment and calculate composite measures of efficacy. Any unusual values will be 
reported as AEs/SAEs where appropriate and values of CRP will be recorded at each visit to allow 
calculation of composite measures of efficacy 
8.8. Discontinuation/Withdrawal of Participants from Trial Treatment 
Each participant has the right to withdraw from the trial at any time, with data collected up to the point 
of withdrawal will be retained and used in the analysis as stated in the PIS. If appropriate they may remain 
in the cohort study unless they wish to be withdrawn from MONITOR as well.   
In addition, the Investigator may discontinue a participant from the trial treatment at any time if the 
Investigator considers it necessary for any reason including: 
 
Pregnancy 
 
Ineligibility (either arising during the trial or retrospectively having been overlooked at screening) 


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 
Significant protocol deviation 
 
Significant non-compliance with treatment regimen or trial requirements 
 
An adverse event which requires discontinuation of the trial medication or results in inability to 
continue to comply with trial procedures 
 
Disease progression which requires discontinuation of the trial medication or results in inability to 
continue to comply with trial procedures 
 
Withdrawal of Consent 
 
Loss to follow up 
 
Requirement of more than 2 local intra-articular injections of steroid to a single joint within a 24 
week time period 
If the participant withdraws from active treatment in the study, Participants will still be asked to complete 
follow up with data collected at planned time points, unless they indicate that they wish to withdraw from 
follow-up.   
If Participants require DMARD therapy, they will be offered rescue therapy as per usual clinical care but 
will be asked to continue with data collection for the trial. Withdrawn Participants will not be replaced.  
The reason for withdrawal will be recorded in the Case Report Form (CRF).  If the participant is withdrawn 
from treatment due to an adverse event, the Investigator will arrange for additional follow-up visits or 
telephone calls as required until the adverse event has resolved or stabilised. 
8.9. Discontinuation/Withdrawal of a site 
Recruitment and screening data will be monitored by the trial team.  This will also be reviewed by the Trial 
Management Group (TMG) and the Trial Steering Committee (TSC).  Where necessary, after appropriate 
support, if a site has persistent low recruitment a site may be required to close and resources used to 
establish another site. 
8.10. Definition of End of Trial 
The end of study is when all participant visits are complete and all data has been entered and queries 
closed. 
9. INVESTIGATIONAL MEDICINAL PRODUCT (IMP) 
9.1. IMP Description 
 Methylprednisolone Acetate and Triamcinolone are NHS supply and will be provided by the NHS 
pharmacy. Pharmacy will be responsible for labelling the IMPs in accordance with the requirements of the 
Medicines for Human Use (Marketing Authorisations Etc.) Regulations 1994. 
Formulation and storage of IMPs are in line with the manufacturers’ recommendations. For further details 
refer to the SmPC for each IMP. A reference copy can be found in the Investigator and Pharmacy Site Files. 
OCTRU will provide labels for all IMPs (non-trial stock) for use in accordance with the requirements of the 
Medicines for Human Use (Clinical Trials) Regulations 2004 (and amended in 2006). The pharmacy at each 
NHS site will be responsible for applying the labels the drug in accordance with the above legislation. 
Methylprednisolone acetate BP  


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This will be supplied as a sterile aqueous suspension in vials containing 40 mg methylprednisolone acetate, 
macrogol, sodium chloride, myristyl-gamma-picolinium chloride and sterile water for injections. 
This drug will be used for local injections given as intra-articular injections to inflamed joints or local 
injections to active enthesitis around tendon insertions.  In the case of multiple active joints, an 
intramuscular injection of methylprednisolone acetate can be used instead of intra-articular injections.  
Each vial of methylprednisolone acetate will be used as supplied.  Doses of between 10 and 120mg of 
methylprednisolone will be used according to the table below: 
Joint
Dose
Small joint/enthesis e.g. fingers
10-20 mg
Medium joint/enthesis e.g. wrist
20-40 mg
Large joint e.g. knee
40-80 mg
Intramuscular injection
80-120 mg
Details of how these will be used are given further in section 4.1 on interventions. 
Triamcinolone  
This will be supplied as a sterile aqueous suspension in vials containing 40mg triamcinolone, benzyl alcohol, 
polysorbate 80m sodium carboxymethylcellulose, sodium chloride and sterile water for injections. 
This drug will be used for local injections given as intra-articular injections to inflamed joints or local 
injections to active enthesitis around tendon insertions.  In the case of multiple active joints, an 
intramuscular injection of triamcinolone can be used instead of intra-articular injections.  Each vial of 
triamcinolone will be used as supplied.  Doses of between 10 and 80mg of triamcinolone will be used 
according to the table below: 
Joint
Dose
Small joint/enthesis e.g. fingers
10-20 mg
Medium joint/enthesis e.g. wrist
20-40 mg
Large joint eg knee
40 mg
Intramuscular injection
80-120 mg
Details of how these will be used are given further in section 4.1 on interventions. 
9.2. Storage of IMP 
Vials of methylprednisolone acetate and triamcinolone will be stored at room temperature and do not 
need to be protected from light. 
9.3. Compliance with Trial Treatment 
The methylprednisolone acetate or triamcinolone will be given by one of the study doctors or nurses in 
the form of an intra-articular or intra-muscular injection.  The dose of glucocorticoid actually given will be 
recorded. 
9.4. Accountability of the Trial Treatment 
Methylprednisolone and Triamcinolone supplied and used for the trial will be recorded in the trial eCRF.  
9.5. Concomitant Medication 
There are no specifically excluded concomitant medications although some drugs are contraindicated 
alongside IMPs in this protocol (e.g. sulphonamides).  Any new therapies for other conditions should only 


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be prescribed if safe alongside any DMARD therapy supplied as rescue therapy within the trial.  Participants 
will be aware of their treatments as this trial is open label as will their general practitioner.  We expect 
that the majority of Participants will take non-steroidal anti-inflammatory drugs or other analgesics for 
joint pain and the doses of these will be recorded. 
9.6. Post-trial Treatment 
All therapies used within this trial are routinely used in NHS practice.  Any participant who has responded 
well to an IMP in the study (e.g. NSAIDs or steroid injections) will be eligible to continue with these as 
standard NHS supply. 
 
10. SAFETY REPORTING 
10.1. Definitions 
Adverse Event (AE) 
Any untoward medical occurrence in a participant to whom a medicinal 
product has been administered, including occurrences which are not 
necessarily caused by or related to that product. 
Adverse Reaction (AR) 
 
An untoward and unintended response in a participant to an investigational 
medicinal product which is related to any dose administered to that 
participant. 
The phrase "response to an investigational medicinal product" means that 
a causal relationship between a trial medication and an AE is at least a 
reasonable possibility, i.e. the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional or 
the Sponsor as having a reasonable suspected causal relationship to the 
trial medication qualify as adverse reactions. 
Serious Adverse Event 
(SAE) 
A serious adverse event is any untoward medical occurrence that: 
 results in death 
 is life-threatening 
 requires inpatient hospitalisation or prolongation of existing 
hospitalisation 
 results in persistent or significant disability/incapacity 
 consists of a congenital anomaly or birth defect. 
Other ‘important medical events’ may also be considered serious if they 
jeopardise the participant or require an intervention to prevent one of the 
above consequences. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an 
event in which the participant was at risk of death at the time of the event; 
it does not refer to an event which hypothetically might have caused death 
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Serious Adverse Reaction 
(SAR) 
An adverse event that is both serious and, in the opinion of the reporting 
Investigator, believed with reasonable probability to be due to one of the 
trial treatments, based on the information provided. 
Suspected Unexpected 
Serious Adverse Reaction 
(SUSAR) 
A serious adverse reaction, the nature and severity of which is not 
consistent with the information about the medicinal product in question 
set out: 
 in the case of a product with a marketing authorisation, in the summary 
of product characteristics (SmPC) for that product 
 
NB: to avoid confusion or misunderstanding of the difference between the terms “serious” and “severe”, 
the following note of clarification is provided: “Severe” is often used to describe intensity of a specific 
event, which may be of relatively minor medical significance. “Seriousness” is the regulatory definition 
supplied above. 
Any pregnancy occurring during the clinical trial and the outcome of the pregnancy should be recorded 
and followed up for congenital abnormality or birth defect, at which point it would fall within the definition 
of “serious”. 
10.2. Causality 
The relationship of each adverse event to the trial medication must be determined by a medically qualified 
individual according to the following definitions: 
Related: The adverse event follows a reasonable temporal sequence from trial medication administration. 
It cannot reasonably be attributed to any other cause. 
Not Related: The adverse event is probably produced by the participant’s clinical state or by other modes 
of therapy administered to the participant. 
10.3. Procedures for Recording Adverse Events 
All adverse events will not be collected in this trial as all the IMPs are licenced, currently used in PsA and 
have well documented safety profiles. Only adverse events of special interest (either extra-articular 
manifestations of the disease or those likely to be related to the therapy used for PsA) occurring during 
the study will be collected at each study visit by patient questionnaire and physician report as below: 
 
 Participant reported 
o Nausea/vomiting 
o Heartburn/dyspepsia 
o Diarrhoea 
o Fatigue 
o Hair loss 
o Injection site reaction 
 
Physician reported 
o Infections 
o Liver function test abnormalities 


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o Neutropenia/leucopenia 
o Uveitis 
The following information will be recorded: date of onset and end date, severity, assessment of 
relatedness to trial medication and action taken.  The severity of events will be assessed on the following 
scale:  1 = mild, 2 = moderate, 3 = severe.  Follow-up information should be provided as necessary. 
It will be left to the Investigator’s clinical judgment to decide whether or not an AE is of sufficient severity 
to require the participant’s removal from treatment.  A participant may also voluntarily withdraw from 
treatment due to what he or she perceives as an intolerable AE.  If either of these occurs, the participant 
would be asked to continue follow up for the study.  If they also withdraw from all trial follow up, we would 
request that they undergo an end of trial assessment and be given appropriate care under medical 
supervision until symptoms cease, or the condition becomes stable. 
10.4. Reporting Procedures for Serious Adverse Events 
All SAEs occurring during the trial and until 4 weeks after the final visit that are observed by the Investigator 
or reported by the participant, will be recorded. 
All SAEs must be reported on the SAE reporting form to OCTRU and the study team within 24 hours of the 
Site Study Team becoming aware of the event.  They will perform an initial check of the report, request 
any additional information, and ensure it is reviewed by the Medical Monitor.  It will also be reviewed in 
the safety report at the next meeting of the Data Safety and Monitoring Committee.  All SAE information 
must be recorded on an SAE form and faxed, or scanned and emailed, to OCTRU.  Additional and further 
requested information (follow-up or corrections to the original case) will be detailed on a new SAE Report 
Form and faxed/emailed to OCTRU.  Any SAEs that are considered related to drug and unexpected (i.e. 
suspected unexpected serious adverse reactions or SUSARs) will also be reported to the sponsor (the 
Clinical Trials and Research Governance or CTRG at the University of Oxford). 
10.5. Expectedness 
The SAE form will be reviewed by the CI, who together with the trial management team in the OCTRU 
office will make an independent assessment of causality and will perform an assessment of expectedness, 
determined according to the Summary of Product Characteristics. Additional and further requested 
information (follow-up or corrections to the original case) will be detailed on a new SAE Report Form and 
faxed or scanned and emailed to the trial office. 
10.6. SUSAR Reporting 
All SUSARs will be reported by OCTRU on behalf of the CI to the MHRA and to the REC and other parties as 
applicable. For fatal and life-threatening SUSARS, this will be done no later than 7 calendar days after 
OCTRU is first aware of the reaction. Any additional relevant information will be reported within 8 calendar 
days of the initial report. All other SUSARs will be reported within 15 calendar days. 
PIs will be informed of all SUSARs for the relevant IMP for all studies with the same Sponsor, whether or 
not the event occurred in the current trial. 
 
10.7. Development Safety Update Reports 


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The DSUR will be submitted in accordance with the OCTRU SOP, on behalf of the CI  once a year throughout 
the clinical trial, or on request, to the MHRA, RES, HRA (where required)and Sponsor. 
11. STATISTICS 
Full details of the statistical analysis will be provided in a separate statistical analysis plan (SAP) which will 
be drafted early in the trial and finalised prior to the primary analysis data lock. Stata (StataCorp LP) or 
other appropriate validated statistical software will be used for analysis. A summary of the planned 
statistical analysis is included here. 
11.1. Description of Statistical Methods 
Specific feasibility analyses include the calculation of the proportions of:  
 
eligible  Participants in the cohort over the recruitment period for POISE 
 
eligible  Participants consenting into the POISE trial 
 
Participants requiring escalation to DMARD therapy within the first 48 weeks. 
If feasibility of such a trial is confirmed based on the assessments above, then the other data collected 
within the study will be used to plan and design a future RCT.  This would be an independent study that 
would not reuse data from these participants.  However the data from this feasibility study will allow us to 
examine the descriptive statistics around the different outcome measures to allow development of a 
sample size and to plan which outcomes would be chosen as primary and secondary key outcomes.  To aid 
design of a future RCT, analysis will focus on descriptive statistics and confidence interval estimation rather 
than formal hypothesis testing as this is not a powered study. Descriptive statistics will be produced by 
trial arm for baseline data assessing PsA phenotype and disease activity. Outcome measures, including 
PASDAS and PSAID, will be summarized at the different follow-up time points. Estimates of the differences 
in outcomes between the groups and corresponding 95% confidence intervals will be presented for the 48 
weeks follow-up time point. Estimates of the PASDAS outcomes at 48 weeks will be used to power any 
future definitive trial.  Reported tolerance, particularly those side effects related to treatments will be 
presented for both groups  
Reasons for non-consent and any suggestions for improving the study design as well as the feasibility of 
outcomes will be considered when designing any future definitive trial. 
11.2. Health Economics analysis 
The economic evaluation will estimate the cost effectiveness of the proportion of Participants not offered 
DMARD therapy during the 48 week trial period in adults with mild non-progressive disease. Primary, 
Community and Social care service use will be collected at 24 weeks and 48 weeks post randomisation 
using patient self-reported questionnaires. The data collected will also record indirect costs as well as 
direct non-medical costs. Unit cost data will be obtained from national databases such as the British 
National Formulary and PSSRU Costs of Health and Social Care[39]. 
HRQoL will be estimated using the EuroQol (EQ-5D-5L[36]). Trial Participants will be asked to complete 
EuroQol (EQ-5D) at baseline, 24 weeks and 48 weeks post randomisation. Responses to the EQ-5D will be 
converted into multi-attribute utility scores using established algorithm[40, 41].  A within trial comparison 
will be conducted from a UK NHS and Personal Social Services perspective (PSS) using the trial data[42]. 
The outputs of the cost-effectiveness analysis will be descriptive only given the sample size in this 


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feasibility study and presented in terms of expected Incremental Cost Effectiveness Ratios (ICERs); ΔCosts/ 
ΔQALY , where , ΔCosts is the difference in total costs between the interventions  and  ΔQALY is the 
difference in utility between interventions),The Number of Participants 
As a feasibility study, one of our key outcomes is the recruitment rate itself.  Publications suggest a sample 
size of 12-30 patients per arm for a feasibility study [36, 37] and therefore a maximum of 60 Participants 
will be randomised in this study in a 1:1 ratio.   
11.3. The Level of Statistical Significance 
To aid design of a future RCT, analysis will focus on descriptive statistics and confidence interval estimation 
rather than formal hypothesis testing.  
11.4. Criteria for the Termination of the Trial 
In the light of the interim data and other evidence from relevant studies, the DSMC will inform the TSC if 
there is proof beyond reasonable doubt that the data indicate the trial should be terminated. A decision 
to inform the TSC of such a finding will in part be based on statistical considerations (appropriate proof 
beyond reasonable doubt cannot be specified precisely). Both the DSMC and TSC will follow appropriate 
charters drawn up prior to the start of the trial. 
11.5. Procedure for Accounting for Missing, Unused, and Spurious Data. 
Missing data will be reported but not taken into account when presenting descriptive statistics.  Any 
pattern to missing data (suggesting that certain outcomes are not recorded well) will be investigated to 
inform a future trial design. 
11.6. Inclusion in Analysis 
The intention to treat population will include those who have been offered the treatment intervention or 
those randomised to stay in the cohort as controls, regardless of whether they accepted the offered 
treatment or received the intervention. Participants will be analysed based on their randomised groups. 
Numbers of Participants who actually received the intervention will also be summarised as this will provide 
additional information to power the future definitive study. 
Information on eligibility and willingness to consent to the feasibility study will be taken from the 
MONITOR PsA cohort study. 
11.7. Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
A detailed statistical analysis plan will be drawn up prior to participant recruitment or early in the trial with 
review and appropriate sign-off following OCTRU SOPs. Any changes to the statistical analysis plan during 
the trial will be subject to the same review and sign-off procedure with details of changes being included 
in the new version. Any changes/deviations from the final SAP will be described and justified in protocol 
and/or in the final report, as appropriate. 
12. DATA MANAGEMENT 
12.1. Source Data 
Source documents are where data are first recorded, and from which Participants’ CRF/eCRF data are 
obtained. These include, but are not limited to, hospital records (from which medical history and previous 


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and concurrent medication may be summarised into the CRF/eCRF), clinical and office charts, laboratory 
and pharmacy records, diaries, microfiches, radiographs, and correspondence. 
CRF/eCRF entries will be considered source data if the CRF/eCRF is the site of the original recording (e.g. 
there is no other written or electronic record of data).  All documents will be stored safely in confidential 
conditions. On all trial-specific documents, other than the signed ICF, the participant will be referred to by 
the trial participant number/code, not by name. 
12.2. Access to Data 
Direct access will be granted to authorised representatives from the Sponsor, host institution and the 
regulatory authorities to permit trial-related monitoring, audits and inspections. All data and 
documentation will be stored in accordance with regulatory requirements and access to the data will be 
restricted to authorised study personnel.  (OCTRU) will securely hold the database. 
12.3. Data Recording and Record Keeping 
Data collection will be performed alongside clinical NHS appointments and data will be inputted directly 
to the electronic clinical record form (eCRF).  Baseline data will be collected from Participants and/or the 
research team and recorded on eCRF.  Data will also be collected for the study follow up time frames, and 
will be via eCRF or via telephone call for collection of core data. Where telephone follow up is used, a 
member of the central study team will carry out data collection directly onto the follow up eCRF. 
Upon receipt of questionnaires/CRFs, appropriate data quality and validation checks will be carried out.   
Study documentation will be retained for a minimum of 15 years after completion of study-related 
activities.  Collaborating sites are delegated the responsibility of archiving local essential documents 
(including the ISF) in an appropriate secure environment. The study office will archive the central Trial 
Master File (TMF) and associated documents according to University of Oxford policy and this may include 
the use of an external professional archiving site. 
All data will be processed according to the compliance with applicable data protection legislation, and all 
documents will be stored safely in confidential conditions.  On all study-specific documents, other than 
the signed ICF, the participant will be referred to by their study number/code, not by name.  Identifiable 
contact information will be stored separately from study data. 
Oxford, Coventry and Newcastle:  Participants will complete their PROMs on a tablet computer using a 
software developed by the OCTRU.  This will securely store the data on a secure server within a university 
of Oxford facility at the John Radcliffe Hospital alongside data entered by the healthcare team.   Participant 
level permissions will allow access to their data only.  Clinical history, examination and medication data 
will be recorded directly into the same system by the clinical assessor. 
Bath:  Participants will complete their PROMs on a tablet computer using a software called Meridian 
developed for the Royal National Hospital for Rheumatic Diseases (RNHRD).  This will securely store the 
data on a secure server within the locked Rheumatology Department’s Facilities at the RNHRD alongside 
data entered by the healthcare team.  Participant level permissions will allow access to their data 
only.  Clinical history, examination and medication data will be recorded directly into Meridian by the 
clinical assessor. The entirety of the study-related clinical data can be securely sent from Meridian to the 
sponsor in Oxford for storage and analysis. 


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Cambridge:  Participants will complete their PROMs on a tablet computer using a software called MyChart, 
that is an extension of EPIC; a fully integrated electronic participant record system. MyChart transmits 
PROMS data securely to EPIC. Clinical history, examination and medication data will be recorded directly 
into EPIC by the clinical assessor. The entirety of the study-related clinical data can be securely sent from 
EPIC to the sponsor in Oxford for storage and analysis. EPIC and MyChart are regulated by the Caldicott 
Guardian and Data Protection Officer at Cambridge University Hospitals NHSFT.  
Data will be transferred to OCTRU as the coordinating centre from other centres via the secure e-CRF. Any 
other material transferred (e.g. consent forms) will be done using secure encrypted data transfer portals 
in compliance with OCTRU SOPs.  
A data management and sharing plan will be drawn up which will fully explain all aspects of data 
management. 
13. ORGANISATION 
13.1. Project timetable and milestones 
The aim is to recruit a maximum of 60 Participants to the trial over a period of 30 months.   
13.2. Trial Steering Committee  
The Trial Steering Committee (TSC) provides overall supervision of the cohort and the trial on the behalf 
of the funder and is chaired by an Independent Member.  The TSC abides by the OCTRU Standard Operating 
Procedure and the OCTRU TSC Charter which is based on the MRC Clinical Trials Unit template.  The TSC 
will monitor study progress and conduct and advise on scientific credibility.  Meetings of the TSC will take 
place at least once a year during the participant recruitment period. 
13.3. Trial Management Group 
The Trial Management Group (TMG) is made up of the Investigators listed on the front of this protocol, 
and staff working on the project within OCTRU and NDORMS.  This group will oversee the day-to-day 
running of the trial and will meet regularly.   
13.4. Data Safety and Monitoring Committee 
A Data Safety and Monitoring Committee (DSMC) will be appointed to safeguard the interests of the trial 
Participants to assess the safety and efficacy of the interventions during the trial, and to monitor the 
overall conduct of the trial, protecting its validity and credibility. The DSMC will be independent of the trial 
investigators and sponsor and will adopt a charter that defines its terms of reference and operation in 
relation to oversight of the trial. It will meet at least every 12 months over the duration of the trial. The 
DSMC will not be asked to perform any formal interim analyses of effectiveness. It will, however, review 
accruing data and summaries of that data presented by treatment group and will assess the screening 
algorithm against the eligibility criteria. It will also consider emerging evidence from other related trials or 
research and review any related SAEs that have been reported. The DSMC may advise the chair of the Trial 
Steering Committee at any time if, in its view, the trial should be stopped for ethical reasons, including 
concerns about participant safety or clear evidence of the effectiveness of one of the treatments. The 
DSMC will comprise an independent medically qualified clinician, statistician, and other researchers. 


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The DSMC for this study will also cover the cohort study MONITOR-PsA to allow cohesive review of any 
safety issues in this TWiCs study. 
13.5. Local Co-ordination 
Each participating site will identify a local PI and local research clinician (as necessary).  The responsibility 
of local research clinicians will be to: 
1. Be familiar with the trial 
2. Liaise with the coordinating team in Oxford 
3. Disseminate MONITOR PsA and POISE protocols and information to staff involved in the trial 
locally 
4. Ensure mechanisms are in place to facilitate the recruitment of eligible  Participants, monitor 
recruitment locally and identify barriers to recruitment and work towards solving them 
5. Ensure timely consenting of  Participants 
6. Work with local Research and Development staff to facilitate approvals  
7. Deal promptly with missing data queries and return these to the study office 
8. Facilitate other aspects of local collaboration as appropriate 
9. Make all data available for verification, audit and inspection purposes as necessary  
10. Ensure participant confidentiality is respected by all persons at all times 
11. The PI at each site will identify local staff who will be responsible for delegated duties.  The 
Delegation Log should be updated accordingly.  New staff should be trained and added to 
the log as the study progresses.  When the Delegation Log is updated, a copy should be sent 
to the study coordinating office in Oxford.  The Delegation Log is part of the working file and 
must be updated when any responsibilities are delegated locally.  A copy of the updated 
version of the log must be sent to the study office. 
14. QUALITY ASSURANCE PROCEDURES 
The trial will be conducted in accordance with the current approved protocol, GCP, relevant regulations 
and SOPs. 
Regular monitoring will be performed according to GCP. Data will be evaluated for compliance with the 
protocol and accuracy in relation to source documents. Following written standard operating procedures, 
the team within OCTRU will verify that the clinical trial is conducted and data are generated, documented 
and reported in compliance with the protocol, GCP and the applicable regulatory requirements.  A 
Monitoring Plan will be developed according to OCTRU’s SOPS which involves a risk assessment.  The 
monitoring activities are based on the outcome of the risk assessment and may involve central monitoring 
and site monitoring. 
A Data Safety and Monitoring Committee (DSMC) will be appointed to safeguard the interests of the trial 
Participants to assess the safety and efficacy of the interventions during the trial, and to monitor the 
overall conduct of the trial, protecting its validity and credibility.   Details of the DSMC are found in section 
13.4. 
15. 
SERIOUS BREACHES 


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The Medicines for Human Use (Clinical Trials) Regulations contain a requirement for the notification of 
"serious breaches" to the MHRA within 7 days of the Sponsor becoming aware of the breach. 
A serious breach is defined as “A breach of GCP or the trial protocol which is likely to affect to a significant 
degree –  
(a) the safety or physical or mental integrity of the subjects of the trial; or 
(b) the scientific value of the trial”. 
In the event that a serious breach is suspected the Sponsor must be contacted within 1 working day. In 
collaboration with the C.I., the serious breach will be reviewed by the Sponsor and, if appropriate, the 
Sponsor will report it to the REC committee, MHRA and the NHS host organisation within seven calendar 
days. 
16. 
ETHICAL AND REGULATORY CONSIDERATIONS 
16.1. Declaration of Helsinki 
The Investigator will ensure that this trial is conducted in accordance with the principles of the Declaration 
of Helsinki.  
16.2. Guidelines for Good Clinical Practice 
The Investigator will ensure that this trial is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
16.3. Approvals 
The protocol, ICF, PIS and any proposed advertising material will be submitted to an appropriate (REC), 
HRA MHRA, and host institution(s) for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
16.4. Reporting 
The CI shall submit once a year throughout the clinical trial, or on request, an Annual Progress Report to 
the REC, HRA (where required), host organisation and Sponsor.  In addition, an End of Trial notification and 
final report will be submitted to the MHRA, the REC, host organisation and Sponsor. 
16.5. Participant Confidentiality 
The trial staff will ensure that the Participants’ anonymity is maintained.  The Participants will be identified 
only by a participant ID number on all trial documents and any electronic database, with the exception of 
the CRF/eCRF, where participant initials may be added.  All documents will be stored securely and only 
accessible by trial staff and authorised personnel. The trial will comply with applicable data protection 
legislation,  which requires data to be anonymised as soon as it is practical to do so. Electronic data transfer 
will be encrypted means. 
16.6. Expenses and Benefits 


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Reasonable travel expenses for any visits additional to normal care will be reimbursed on production of 
receipts, or a mileage allowance provided as appropriate. 
16.7. Other Ethical Considerations 
Vulnerable Participants and Participants who are unable to consent for themselves will not be recruited to 
this study. 
17. 
FINANCE AND INSURANCE 
17.1. Funding 
This study is funded by a National Institute of Health Research Clinician Scientist Award for Dr Laura Coates 
(ref CS-2016-16-016) through the University of Oxford. 
17.2. Insurance 
The University has a specialist insurance policy in place which would operate in the event of any participant 
suffering harm as a result of their involvement in the research (Newline Underwriting Management Ltd, at 
Lloyd’s of London).  NHS indemnity operates in respect of the clinical treatment that is provided. 
18. 
PUBLICATION POLICY 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any 
other publications arising from the study.  Authors will acknowledge that the study was funded by the 
NIHR. Authorship will be determined in accordance with the ICMJE guidelines and other contributors will 
be acknowledged. 
19. 
REFERENCES 
 
1. 
Helliwell, P.S., O. FitzGerald, and J. Fransen, Composite disease activity and responder indices for 
psoriatic arthritis: a report from the GRAPPA 2013 meeting on development of cutoffs for both 
disease activity states and response. J Rheumatol, 2014. 41(6): p. 1212-7. 
2. 
Helliwell, P.S., et al., The development of candidate composite disease activity and responder 
indices for psoriatic arthritis (GRACE project). Annals of the Rheumatic Diseases, 2012(online first 
17/07/2012). 
3. 
Villani, A.P., et al., Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: 
Systematic review and meta-analysis. J Am Acad Dermatol, 2015. 73(2): p. 242-8. 
4. 
National Institute for Health and Care Excellence, Psoriatic arthritis - etanercept, infliximab and 
adalimumab. 2010. 
5. 
Kane, D., et al., A prospective, clinical and radiological study of early psoriatic arthritis: an early 
synovitis clinic experience. Rheumatology, 2003. 42(12): p. 1460-8. 
6. 
Gladman, D.D., et al., Longitudinal study of clinical and radiological progression in psoriatic 
arthritis. Journal of Rheumatology, 1990. 17(6): p. 809-12. 
7. 
Sokoll, K.B. and P.S. Helliwell, Comparison of Disability and Quality of Life in Rheumatoid and 
Psoriatic Arthritis. Journal of Rheumatology, 2001. 28(8): p. 1842-1846. 
8. 
Gladman, D.D., et al., Mortality studies in psoriatic arthritis: results from a single outpatient center. 
II. Prognostic indicators for death. Arthritis & Rheumatism, 1998. 41(6): p. 1103-10. 


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9. 
Haroon, M., et al., High prevalence of metabolic syndrome and of insulin resistance in psoriatic 
arthritis is associated with the severity of underlying disease. J Rheumatol, 2014. 41(7): p. 1357-
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Huscher, D., et al., Cost of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis 
and systemic lupus erythematosus in Germany. Annals of the Rheumatic Diseases, 2006. 65(9): p. 
1175-83. 
11. 
Helliwell, P.S. and V. Wright, Psoriatic arthritis: clinical features, in Rheumatology, J.H. Klippel and 
P.A. Dieppe, Editors. 1998, Mosby: London. p. 6.21.1 - 6.21.8. 
12. 
Gladman, D.D., Natural history of psoriatic arthritis. Baillieres Clin Rheumatol, 1994. 8(2): p. 379-
94. 
13. 
Bond, S.J., et al., Predictors for radiological damage in psoriatic arthritis: results from a single 
centre. Annals of the Rheumatic Diseases, 2007. 66(3): p. 370-6. 
14. 
Gladman, D.D. and V.T. Farewell, Progression in psoriatic arthritis: role of time varying clinical 
indicators. Journal of Rheumatology, 1999. 26(11): p. 2409-13. 
15. 
Gladman, D.D., V.T. Farewell, and C. Nadeau, Clinical indicators of progression in psoriatic arthritis: 
multivariate relative risk model. Journal of Rheumatology, 1995. 22(4): p. 675-9. 
16. 
Marzo-Ortega, H., et al., A randomized controlled trial of early intervention with intraarticular 
corticosteroids followed by sulfasalazine versus conservative treatment in early oligoarthritis. 
Arthritis Rheum, 2007. 57(1): p. 154-60. 
17. 
Marzo-Ortega, H., L. Cawkwell, and M.J. Green, Early oligoarthritis. Rheum Dis Clin North Am, 
2005. 31(4): p. 627-39. 
18. 
Coates, L.C., et al., Reduced joint counts misclassify patients with oligoarticular psoriatic arthritis 
and miss significant numbers of patients with active disease. Arthritis Rheum, 2013. 65(6): p. 1504-
9. 
19. 
Marin, J., et al., Utility of Power Doppler Ultrasound-Detected Synovitis for the Prediction of Short 
Term Flare in Psoriatic Arthritis Patients in Clinical Remission. Arthritis Rheumatol, 2015. 67 (suppl 
10). 
20. 
Relton, C., et al., Rethinking pragmatic randomised controlled trials: introducing the "cohort 
multiple randomised controlled trial" design. BMJ, 2010. 340: p. c1066. 
21. 
Ficjan, A., et al., Ultrasound composite scores for the assessment of inflammatory and structural 
pathologies in Psoriatic Arthritis (PsASon-Score). Arthritis Res Ther, 2014. 16(5): p. 476. 
22. 
Gossec, L., et al., European League Against Rheumatism (EULAR) recommendations for the 
management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis, 
2016. 75(3): p. 499-510. 
23. 
National Institute for Health and Care Excellence, Golimumab for the treatment of psoriatic 
arthritis. 2011. 
24. 
National Institute for Health and Care Excellence, Ustekinumab for treating active psoriatic 
arthritis. 2015. 
25. 
National Institute for Health and Care Excellence, Apremilast for treating active psoriatic arthritis. 
2017. 
26. 
Atkinson, M.J., et al., Validation of a general measure of treatment satisfaction, the Treatment 
Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. 
Health Qual Life Outcomes, 2004. 2: p. 12. 
27. 
Healy, P.J. and P.S. Helliwell, Measuring clinical enthesitis in psoriatic arthritis: assessment of 
existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum, 
2008. 59(5): p. 686-91. 
28. 
Maksymowych, W.P., et al., Development and validation of the Spondyloarthritis Research 
Consortium of Canada (SPARCC) Enthesitis Index. Annals of the Rheumatic Diseases, 2009. 68(6): 
p. 948-53. 
29. 
van der Heijde, D., et al., Psoriatic arthritis imaging: a review of scoring methods. Annals of the 
Rheumatic Diseases, 2005. 64 Suppl 2: p. ii61-4. 


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30. 
Wassenberg, S., et al., A method to score radiographic change in psoriatic arthritis. Z Rheumatol, 
2001. 60(3): p. 156-66. 
31. 
Fries, J.F., et al., Measurement of patient outcome in arthritis. Arthritis Rheum, 1980. 23(2): p. 137-
45. 
32. 
Gossec, L., et al., A patient-derived and patient-reported outcome measure for assessing psoriatic 
arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) 
questionnaire, a 13-country EULAR initiative. Ann Rheum Dis, 2014. 73(6): p. 1012-9. 
33. 
Husted, J.A., et al., Validating the SF-36 health survey questionnaire in patients with psoriatic 
arthritis. J Rheumatol, 1997. 24(3): p. 511-7. 
34. 
Herdman, M., et al., Development and preliminary testing of the new five-level version of EQ-5D 
(EQ-5D-5L). Qual Life Res, 2011. 20(10): p. 1727-36. 
35. 
Zhang, W., et al., Validity of the work productivity and activity impairment questionnaire--general 
health version in patients with rheumatoid arthritis. Arthritis Res Ther, 2010. 12(5): p. R177. 
36. 
Julious, S.A., Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat, 2005. 4(4): p. 
287-291. 
37. 
Lancaster, G.A., S. Dodd, and P.R. Williamson, Design and analysis of pilot studies: 
recommendations for good practice. J Eval Clin Pract, 2004. 10(2): p. 307-12. 
20. APPENDIX A:  RECRUITMENT AND INCLUSION TO TRIAL 
 
 


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21. 
APPENDIX B:  TRIAL FLOW CHART 
 
 
 
 


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22. 
APPENDIX C:  SCHEDULE OF PROCEDURES 
 
Procedures
Baseline 
cohort/ Trial 
Screening 
Visits 
Baseline  
 
 
 
 
Week -4 to 0
Week 0 
Week 12 
Week 24 
Week 36 
Week 48 
Informed consent 
 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Medical history 
 
X 
X 
X 
X 
X 
Inclusion/exclusion 
criteria assessment 
 
X 
 
 
 
 
Medication 
 
X 
X 
X 
X 
X 
Physical examination 
 
X 
X 
X 
X 
X 
Routine blood tests 
(FBC, U&Es, LFTs, CRP) 
 
X 
X 
X 
X 
X 
Immunology (RF, ACPA) 
 
X 
 
 
 
 
Radiographs of 
hands/feet/spine 
 
X 
 
 
 
X 
Eligibility assessment 
 
X 
 
 
 
 
Randomisation 
X 
 
 
 
 
 
Dispensing of drugs 
within Medication (IA or 
IM corticosteroids 
given) 
 
X 
X 
X 
X 
 
 Adherence  
 
 
X 
X 
X 
X 
68/66 Joint count 
 
X 
X 
X 
X 
X 
Leeds and SPARCC 
enthesitis index 
 
X 
X 
X 
X 
X 
Dactylitis count 
 
X 
X 
X 
X 
X 
Psoriasis assessment 
(PASI and BSA) 
 
X 
X 
X 
X 
X 
Physician VAS 
 
X 
X 
X 
X 
X 
Metrology with BASMI 
(if axial involvement) 
 
X 
 
 
 
X 
Patient questionnaires 
(VAS, HAQ, SF36, PsAID, 
WPAI, BASDAI, BASFI) 
 
X 
X 
X 
X 
X 
TSQM questionnaire 
 
 
X 
X 
X 
X 
EQ-5D-5L questionnaire 
 
X 
 
X 
 
X 
Healthcare utilisation 
data 
 
 
 
X 
 
X 


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US of joints 
(interventional arm 
only) 
 
X 
 
 
 
 
Adverse event 
assessments  
 
X 
X 
X 
X 
X 
Radiographs will be obtained from patient healthcare records as normal care  
 


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23. APPENDIX D:  SAE REPORTING FLOW CHART 
 
 


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24. 
APPENDIX E:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version No.
Date issued
Author(s) 
of 
changes 
Details of Changes made
1 (non 
substantial) 
V2.1
03 July 2018
Laura Coates
1. Section on Contraception  
2. Methylprednisolone Acetate and 
Triamcinolone will be used as 
supplied and not diluted 
2 (Substantial 
Amendment)   
V3.0
05 
Nov 
2018 
Laura Coates
Not approved
3 (Non 
substantial) 
V3.1
10 Jan 2019
Laura Coates
1. Update to CTRG address
2. Terminology 
update 
from 
‘Participants’ to ‘Patients’ 
3. Update Dr Coates phone number 
4. Added eGFR to the inclusion 
criteria section 
5. Clarification to section 4.1 and 8.5 
- Patients in Arm1 will not receive 
an Ultrasound scan.  
6. Clarification provided in the 
Inclusion 
criteria 
section 
on 
contraception. 
7. Addition of eGFR to the efficacy 
bloods 
within 
the 
baseline 
assessment section. 
8. Removal of dilution wording from 
section 4.1 to be consistent with 
section 9.1. 
4 (Substantial 
amendment) 
V5.0
21Mar 2019
Laura 
Coates/Yvonne 
Sinomati 
9. Changes to Data Protection, 
addition 
of 
Coventry 
and 
Newcastle sites, name changed 
from Concomitant Medication to 
Medication 
CRF 
which 
is 
referenced throughout the text 
and in Appendix C. Reference of 
BASMI removed from each of the 
patient 
visits 
to 
only 
be 
performed at baseline, 48 weeks 
and yearly thereafter, BASMI 
section of appendix C updated. 
The two new sites will be using 
OCTRU’s systems under the data 
recording section. 
5 (Substantial 
amendment) 
V6.0
27Aug2019
Laura 
Coates/Yvonne 
Sinomati 
1. Low disease activity (PASDAS) 
and Low impact of disease 
(PSAID) 
removed 
from 
Section 4 and 7.2. ‘A member 
of the research team will 


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undertake
disease activity
assessments blinded’ added 
to section 8.4. 
 
Protocol amendments will be submitted to the Sponsor for approval prior to submission to the REC 
committee or MHRA.