Early detection to improve outcome in people with undiagnosed psoriatic arthritis: the PROMPT research programme including RCT

Background Longitudinal observational studies suggest that patients who present early to secondary care with psoriatic arthritis have a better outcome. Outcome needs to be measured including domains important to patients. Objectives To identify disease activity and impact outcomes important to patients with psoriatic arthritis in comparison to existing ones (Patient-Reported Outcome Measurement Study). To assess the validity of new measures of disease activity in psoriatic arthritis derived from patient engagement (ASSESSment of modified composite disease measures study). To explore patients’ experiences of diagnosis in psoriatic arthritis? (Experiences of screening and diaGnosis from the perspective of pAtients with PSoriasis and psoriatic arthritis study). To identify modifiable risk factors for the development of psoriatic arthritis using the Clinical Practice Research Datalink (EPIdemiology of psoriatiC arthritis study). To compare the performance of screening tools for detecting undiagnosed psoriatic arthritis (COMparison of Psoriatic Arthritis scREening tools study). To investigate the clinical effectiveness (Total bUrDen Of psoRiasis trial) and cost-effectiveness (COSt of screening for Psoriatic Arthritis study) of detecting undiagnosed psoriatic arthritis. Design and methods Mixed methods using data from patient focus groups, a multicentre cohort study, primary care health records (Clinical Practice Research Datalink) and a prospective randomised clinical trial (Total bUrDen Of psoRiasis trial, COMparison of Psoriatic Arthritis scREening tools study, COSt of screening for Psoriatic Arthritis study). Setting and participants Focus groups and cohort studies of 221 patients with psoriatic arthritis including newly diagnosed cases (Patient-Reported Outcome Measurement Study, ASSESSment of modified composite disease measures study, experiences of screening and diaGnosis from the perspective of pAtients with PSoriasis and psoriatic arthritis study) and 2225 patients with psoriasis from primary care not known to have psoriatic arthritis from 135 randomised general practices (COMparison of Psoriatic Arthritis scREening tools study, Total bUrDen Of psoRiasis trial randomised clinical trial, COSt of screening for Psoriatic Arthritis study). Intervention Randomised controlled trial comparing the early identification of psoriatic arthritis by annual rheumatological assessment (enhanced surveillance) in people with psoriasis identified in primary care (n = 1123) with standard care (n = 1102). Participants with suspected inflammatory arthritis were referred to the local rheumatology clinic for an assessment of psoriatic arthritis (enhanced surveillance arm: at baseline, 12 and 24 months; standard care arm: at 24 months). Data sources Cohort studies of incident psoriasis (n = 90,189) or psoriatic arthritis (n = 6783) patients from the Clinical Practice Research Datalink (EPIdemiology of psoriatiC arthritis study). Cost-effective analysis using data collected in Total bUrDen Of psoRiasis trial. Modelling exercise to extrapolate screening performance from Total bUrDen Of psoRiasis trial to long-term costs and quality-adjusted life-years (COSt of screening for Psoriatic Arthritis study). Main outcome measure In Total bUrDen Of psoRiasis trial the primary outcome was the Health Assessment Questionnaire Disability Index at 24 months post registration in participants diagnosed with psoriatic arthritis. Results Patient-Reported Outcome Measurement Study: Patients rated pain and fatigue as the most important outcomes when receiving treatment for psoriatic arthritis. ASSESSment of modified composite disease measures study: Shortened versions of visual analogue scales performed well in detecting treatment change and responsiveness over 6 months. Experiences of screening and diaGnosis from the perspective of pAtients with PSoriasis and psoriatic arthritis study: Missed opportunities for psoriatic arthritis diagnosis has implications for well-being including mental health, and there is a need for provision of psychological support and self-management guidance. Screening for psoriatic arthritis was generally regarded as a positive experience. EPIdemiology of psoriatiC arthritis study: Bayesian networks identified clusters of symptoms that can accurately predict the development of psoriatic arthritis (area under the curve 0.73, 95% CI 0.70 to 0.75). Obesity is a modifiable lifestyle factor that increases the risk of developing psoriatic arthritis and diminishes linearly over a 10-year period with a reduction in body mass index. Diabetes, cardiovascular disease, uveitis and Crohn’s disease are associated with psoriatic arthritis and may appear early in the disease course. COMparison of Psoriatic Arthritis scREening tools study: The Psoriasis Epidemiology Screening Tool questionnaire remains the preferred screening tool, given its simplicity with no significant differences in performance (sensitivity: 0.625, specificity: 0.757, area under the curve 0.787) compared to COmparisoN of ThreE Screening Tools to detect psoriatic arthritis in patients with psoriasis. Total bUrDen Of psoRiasis trial: The primary analysis population consisted of 87 participants with a positive diagnosis of psoriatic arthritis: 64 in enhanced surveillance, 23 in standard care (overall mean Health Assessment Questionnaire Disability Index score at 24 months was 0.45). The adjusted odds ratio for achieving a Health Assessment Questionnaire Disability Index score of 0 at 24 months post registration in enhanced surveillance compared to standard care was 0.64 (95% CI 0.17 to 2.38), and the adjusted odds ratio of achieving a higher (non-zero) Health Assessment Questionnaire Disability Index score at 24 months post registration in enhanced surveillance relative to standard care arm was 1.12 (95% CI 0.67 to 1.86), indicating no evidence of a difference between the two treatment groups (p = 0.6612). COSt of screening for Psoriatic Arthritis study: The within-trial cost-effectiveness analysis suggests that enhanced surveillance may be associated with higher mean quality-adjusted life-years, although the difference was very small (+0.002, 95% CI –0.03 to 0.03), and lower mean costs (−£120.54, 95% CI –£540.57 to £288.99). Using the cost-effectiveness model based on the sensitivity, specificity and the psoriatic arthritis incidence from the Total bUrDen Of psoRiasis trial, Psoriasis Epidemiology Screening Tool is the most expensive and has the highest lifetime quality-adjusted life-years with an incremental cost-effectiveness ratio of £14,964 per additional quality-adjusted life-year compared to CONTEST, CONTESTjt and no screening using a lifetime time horizon. Limitations The Total bUrDen Of psoRiasis trial was underpowered due to a lower proportion of patients developing psoriatic arthritis than expected (87 compared to 148) and disruption to follow-up due to the coronavirus pandemic. COSt of screening for Psoriatic Arthritis study analyses were limited by the extent of missing data. Conclusion The benefit of early detection of psoriatic arthritis in a primary care psoriasis population remains unproven. Surveillance for undiagnosed psoriatic arthritis generally detects mild cases as measured by physical function. Patients rate pain and fatigue as the most important outcomes. Future work Five-year follow-up of Total bUrDen Of psoRiasis trial participants to investigate longer-term benefits of earlier diagnosis comparing treatment arms and to assess risk factors for psoriatic arthritis development is underway. Trial registration This trial is registered as Current Controlled Trials ISRCTN38877516. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-1212-20007) and is published in full in Programme Grants for Applied Research; Vol. 13, No. 6. See the NIHR Funding and Awards website for further award information.