Title: Early detection to improve outcome in patients with undiagnosed psoriatic arthritis
Funder: Department of Health and Social Care

Abstract: Patient and public involvement Our programme directly stems from key areas identified as major priorities for research by NICE guidelines on assessment and management of psoriasis, focus groups of people with PsA, and our own patient research partners. Patient research partners will have an active role in all aspects of the programme. Background and Rationale Psoriatic arthritis (PsA) affects approximately 1 in 3 people with pre-existing psoriasis. However, screening patients with psoriasis for PsA in primary care/dermatology clinics has revealed a high prevalence (14-29%) of undiagnosed disease. Preliminary studies, including our own, have identified a significant need for the earlier diagnosis of PsA. There is indirect evidence that delay in diagnosis results in unfavourable outcome with increased health costs and work disability. There is solid evidence that early treatment lessens long-term disease burden in rheumatoid arthritis but this has not yet been shown for PsA. As psoriasis precedes PsA in ~70% of cases, this provides a unique opportunity to develop an optimal screening strategy to apply to people with psoriasis and determine whether early diagnosis of PsA is clinically and cost effective. From studies we have led on we know that outcome measures for PsA need to be refined to encompass domains that people with PsA have identified as important, particularly fatigue pain, skin disease and work disability. Aims and objectives We aim to provide an evidence-based framework for recommendations on an effective and acceptable screening strategy for the early identification of PsA in people with psoriasis in primary care and their subsequent management by: Theme One: Screening and Early Diagnosis investigating the clinical effectiveness (1A) and cost-effectiveness (1C) of detecting undiagnosed PsA determining an effective screening strategy for early detection of PsA by using patient questionnaires (1B) investigating the role of modifiable risk factors in the development of PsA in people with psoriasis ( 1D) identifying current barriers to diagnosis of PsA (1E) Theme Two: Outcome Measurement in Early Disease ensuring outcome measures encompass aspects of early disease that are important to people with psoriatic arthritis (2A, 2B) Research Plan Theme one: Screening and Early diagnosis Study 1A. We will undertake a two-arm parallel-group cluster randomised controlled trial of enhanced surveillance for PsA versus standard care to determine whether identifying undiagnosed PsA in primary care leads to improved outcomes. The primary outcome will be physical function measured by the Health Assessment Questionnaire (HAQ) at two years. Secondary outcomes will include quality of life assessments, health resource utilisation and work productivity. A total of 138 patients with PsA (69 per arm) are required to be diagnosed to have 80% power for detecting a difference in HAQ scores of 0.35 units at 5% significance level. After adjustment for the cluster design and anticipated 20% withdrawal we require a sample size of 2000 patients across 80 general practices (40 practices per arm). Study 1B. Participants from practices randomised to the enhanced surveillance arm of 1A will be included in a diagnostic accuracy study of the CONTEST and PEST screening questionnaires. A diagnosis of PsA will be made according to the CASPAR criteria by a rheumatologist who is blinded to the questionnaire responses. With 1000 participants the precision of sensitivity is estimated at &plusmn;11.5% and specificity &plusmn;4.8% taking into account practice clustering. Study 1C. A decision analytic model will be developed to estimate the clinical outcomes and cost-effectiveness of the detection of undiagnosed PsA using data from 1A and to compare the cost-effectiveness of PEST and CONTEST. Study 1D. We will use the Clinical Practice Research Datalink to describe the evolution of musculoskeletal symptoms in people with psoriasis, investigate the role of smoking and obesity in PsA development, and describe primary health care resource utilisation pre-diagnosis. Study 1E. We will undertake qualitative work with participants identified through the enhanced surveillance arm of 1A and from routine rheumatology care. Topic guides will address the healthcare experience relating to diagnosis and screening, perceived delays, barriers or facilitators to diagnosis, as well as experiences regarding screening, and recommendations for future patients. Theme two : Outcome Measurement in Early Disease Study 2A. The patient perspective will be explored in focus groups to identify the most relevant patient reported outcome measures for domains important to patients and to incorporate in revised composite measures of disease activity that will be used as outcome measures in 1A and evaluated in 2B Study 2B. Participants with early disease recruited from routine care will be used to evaluate the ability of new and existing measures to distinguish between active and inactive disease using analysis of variance. Dissemination Our regular multidisciplinary programme management group meetings will provide a platform for advice on governance, research progress, discussion and dissemination of findings, development of recommendations and provision of educational materials for relevant stakeholders.

Lay abstract: Psoriatic arthritis (PsA), an inflammatory arthritis, affects approximately 1 in 3 people with pre-existing psoriasis and up to 400,000 people in England. It causes pain, swelling and stiffness in the joints, is accompanied by chronic disfiguring skin disease, and may result in severe disability and reduced quality of life. Up to half of patients with PsA have some level of work disability and 3 in 10 are unemployed. The burden of undiagnosed PsA is high and there is emerging evidence that delay in diagnosis results in worse outcome. Recent NICE Quality Standards for psoriasis stipulate that people with receiving treatment for psoriasis are offered an annual assessment for PsA. Whilst there is good evidence of clear benefit in the early detection of rheumatoid arthritis there is insufficient evidence to confirm that early identification of PsA leads to better outcome. Moreover, a suitably accurate screening questionnaire is not yet available for use in clinical practice. It is essential that we can measure the impact of PsA on patients in ways that they find important rather than domains solely defined by clinicians. The current methods used to measure disease activity and damage in PsA have not been developed with input from people with PsA. We will improve the current measures by identifying domains that are important to people with PsA. Detection We will perform a randomised controlled trial to investigate the overall benefit of earlier diagnosis of PsA (Studies 1A and 1C). The currently recommended questionnaire for screening (PEST) lacks sufficient sensitivity (i.e. it misses many cases), more so for some types of PsA. We have developed a further questionnaire (CONTEST) and will compare its accuracy for the identification of PsA against PEST and the gold standard of rheumatological assessment in people with psoriasis, including those not receiving treatment for psoriasis (Study 1B). We will investigate the evolution of PsA symptoms, reasons for delay and the barriers to diagnosis of PsA (Studies 1D and 1E). Measurement We will identify outcome measures that are meaningful for people with PsA, for example fatigue, pain, skin disease and performance at work, and determine the best way of measuring them (2A). We will then apply these combined methods including clinician and patient-related outcome measures and test their performance prospectively in patients with newly diagnosed psoriatic arthritis (2B). Recommendations The overall outcome of this programme of work will be to deliver a series of evidence-based practical recommendations on screening, referral and outcome measurement for PsA and the cost-effectiveness of such a strategy. Through programme management group and stakeholder meetings the recommendations will inform educational packages, future guideline development, referral pathways and routine clinical care within the NHS for people with psoriasis.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;7.1 INDIVIDUAL CARE NEEDS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;SKIN