Abstract
Objective To determine the annual incidence of psoriatic arthritis (PsA) in a United Kingdom primary care population with preexisting psoriasis (PsO) followed prospectively over 2 years after excluding baseline prevalence of existing disease.
Methods Total Burden of Psoriasis (TUDOR; ISRCTN registry: ISRCTN38877516) was a multicenter, prospective, 2-arm parallel-group cluster randomized controlled trial of the early identification of PsA by annual rheumatological assessment (termed “Enhanced Surveillance”) vs standard care in people with PsO identified in primary care. Incidence of PsA is reported at 12 months and 24 months using patients from the Enhanced Surveillance arm, which allows for the exclusion of patients with prevalent PsA at baseline.
Results Fourteen of 511 participants attending a 12-month screen developed PsA over that interval, giving an incidence of 2.74/100 patient-years (PYs; 95% CI 1.32-4.16). Another 7/444 participants attending the 24-month visit developed PsA, giving an incidence of 1.58/100 PYs (95% CI 0.42-2.74). The combined incidence over 2 years was 2.20/100 PYs (95% CI 1.27-3.13).
Conclusion The estimated annual incidence of PsA over a 2-year period was 2.20/100 PYs, which is in keeping with studies including clinical assessment rather than relying on health records alone. Extended follow-up of the TUDOR cohort with accrual of larger numbers of incident cases will allow risk factors for PsA to be explored in more depth.
Psoriatic arthritis (PsA) is a potentially debilitating form of inflammatory arthritis that affects approximately 20% of the psoriasis (PsO) population worldwide.1 Skin PsO usually precedes the development of PsA by several years,2 affording an opportunity to screen an at-risk group for early detection of PsA. The efficiency and cost effectiveness of screening strategies are dependent on the incidence of the target condition and the potential for alleviating that condition by effective treatment. Studies have shown that delay in diagnosis of PsA is associated with adverse outcomes,3 and patients are now able to access a range of newer, more effective therapeutic agents earlier in the disease pathway.4 Hence, accurate estimates of the incidence of PsA in populations targeted for screening are highly desirable.
Previous studies have shown up to a 10-fold difference in the incidence rate of PsA in PsO populations. A lower incidence rate of around 0.27/100 patient-years (PYs) was found in 2 separate studies that used diagnostic coding records from primary care practices in the United Kingdom.2,5 In a population-based study of clinical records from the United States, the findings were similar, with a 10-year cumulative incidence of 3.1%.6 However, a higher incidence rate of 2.7/100 PYs was reported in a Canadian PsO cohort of 464 patients with PsO who were followed prospectively for at least 1 year and clinically examined for the presence of PsA.7 Other studies have found incidence rates in between the abovementioned values.8
In this work, we use data from the Total Burden of Psoriasis (TUDOR) randomized controlled trial comparing the Enhanced Surveillance arm (involving annual rheumatological assessment) vs standard care for the early detection of PsA in a primary care PsO population. In the Enhanced Surveillance arm, patients with undiagnosed PsA were identified at baseline, and the remaining patients were assessed at 12- and 24-month follow-up, providing a mechanism for estimating the incidence of PsA in a prospective cohort of patients with PsO. We also describe trends for potential risk factors associated with the development of PsA.
METHODS
Study population. The TUDOR trial (ISRCTN registry: ISRCTN38877516) was a multicenter, prospective, 2-arm parallel-group cluster randomized controlled trial of patients with PsO to study the effect of the early detection of PsA.9 Participants in the Enhanced Surveillance arm were recruited from primary care records held in 72 participating practices and were invited to attend a health check that included a screening examination for PsA. Eligible participants were aged 18-70 years at the time of enrollment and did not have a prior diagnosis of PsA, rheumatoid arthritis, or ankylosing spondylitis.
To calculate the yearly incidence of PsA during the study, we solely used data collected as part of the Enhanced Surveillance arm of the trial. Patients who were assigned to the Enhanced Surveillance arm were given clinical assessments at baseline, 12, and 24 months. Clinical assessments included physical examinations, as well as comprehensive questionnaires about their PsO, health-related quality of life, and physical function. All members of the assessment teams had formal training in the instruments used to assess PsA and skin PsO. Those with suspected symptoms of inflammatory arthritis were referred to rheumatology by their general practitioner (GP) for diagnosis. Participants may also have been diagnosed with PsA at any point during the study as a result of routine care by their GP. These patients were identified at their next clinical assessment through medical history questionnaires. Therefore, incident cases were diagnosed either as a result of the clinical assessment and subsequent GP referral, or by GP referral to rheumatology outside of the clinical assessment.
To ensure incident diagnoses, in this analysis, we exclude patients diagnosed with prevalent PsA at baseline.
Statistical analysis. The yearly incidence of PsA in the study was calculated using the number of patients who developed incident PsA, either through referral resulting from clinical assessment or from routine care, divided by the total number of patients who attended the annual assessment. CIs for the incidence are reported as Wald intervals, using the normal approximation to the binomial distribution at 95% coverage.
We also compare baseline characteristics between the group who developed PsA and the group who did not develop PsA during the study period. These characteristics include age, gender, BMI (calculated as weight in kilograms divided by height in meters squared), PsO duration, nail involvement, Psoriasis Area and Severity Index (PASI) score, Health Assessment Questionnaire–Disability Index (HAQ-DI) score, and the result of the Psoriasis Epidemiology Screening Tool (PEST) questionnaire. For this analysis, we excluded patients lost to follow-up before their 24-month appointment and, for each characteristic, excluded patients with missing data.
We report the mean and SD of continuous variables and compare the means between the 2 groups using Welch t test. For continuous variables with nonnormal distributions, we report the median and compare the groups using a Mann-Whitney U test. For categorical variables, we report the proportions, and compare the difference using a chi-square test.
Ethics. The study had NHS Health Research Authority Ethics approval (reference: 16/SW/0161).
RESULTS
Study population. One thousand one hundred twenty-three patients with PsO were recruited from 72 UK GP practices assigned to the Enhanced Surveillance arm of the trial. Seven hundred ninety-three participants attended the baseline clinical assessment, of whom 43 were diagnosed with prevalent PsA. Twenty-one patients were diagnosed with PsA during the study period, all of whom attended their baseline clinical assessment, confirming these were incident cases.
PsA incidence. Of the 511 patients who attended the 12-month clinical assessment, 14 were found to have developed PsA over that interval, giving an incidence of 2.74/100 PYs (95% CI 1.32-4.16). Nine of these 14 were diagnosed as a result of a referral triggered by the clinical assessment, and 5 were found to have been diagnosed as part of routine care during that period. A further 7/444 participants attending the 24-month clinical assessment developed PsA, giving an incidence during the second year of 1.58/100 PYs (95% CI 0.42-2.74). Four of these were diagnosed as a consequence of the clinical assessment, and 3 patients were diagnosed as part of routine care. The combined incidence over the 2-year study period was 2.20/100 PYs (95% CI 1.27-3.13).
Baseline characteristics. Baseline characteristics of the 21 incident PsA cases were compared to the 417 patients who attended their baseline and 24-month clinical assessments and did not develop PsA (Table). Overall, the number of incident cases at 2 years is not sufficiently large enough at this stage to draw statistically significant conclusions. Those who developed PsA were slightly older, and a higher percentage were male. The 2 groups had very similar BMI, PsO duration, HAQ-DI scores, and PASI scores. Those who developed PsA showed a trend toward increased nail involvement compared to the group who did not develop PsA (61.9% vs 45.6%, respectively; difference of 16.3%, 95% CI −4.99 to 37.70). Notably, the 2 groups had a very similar prevalence of positive PEST scores at baseline (23.8% of those who developed PsA vs 25% in the group who did not; difference of −1.2%, 95% CI −19.90 to 17.50).
Baseline characteristic of incident cases of PsA vs controls with PsO alone.
DISCUSSION
Estimates of the incidence of PsA in people with PsO have varied considerably for many possible reasons, including disease heterogeneity, the classification criteria used, and the study setting. Studies based on primary care records alone tend to find a lower incidence of around 0.27/100 PYs.2,5 Comparatively, the annual incidence from a prospective cohort study, in which individuals with PsO were clinically examined, was 2.7/100 PYs.7 In the latter study, patients were recruited mainly from dermatology clinics and phototherapy centers. The higher incidence may reflect increased PsO severity, a known risk factor for PsA.7,8,10 Therefore, more accurate estimates of incidence in primary care require prospective studies accompanied by adequate screening and assessment.
All participants in the TUDOR trial were recruited from primary care and identified as having skin PsO but not PsA from their primary care record code. Those entering the Enhanced Surveillance arm had a baseline assessment that included a screening tool (PEST) for the presence of PsA, and the GP of anyone who was either PEST positive or otherwise suspected of having PsA was asked to refer the participant to secondary care for confirmation of the diagnosis of PsA. Accordingly, 43 cases of prevalent PsA at baseline were identified and eliminated from any subsequent contribution to the calculation of PsA incidence. The PEST as a screening tool is not specific for PsA and was positive at baseline in around one-quarter of cases for both incident cases and those known not to have developed PsA at the 12- and 24-month follow-up, hence providing further reassurance that prevalent cases of PsA had been eliminated at baseline. Together with the low level of physical disability documented at baseline in incident cases (median HAQ-DI score of 0), we can be more confident that the 21 cases of PsA detected at follow-up represent genuine incident cases.
Our combined incidence of PsA over the 2-year study period was 2.20/100 PYs, which was slightly less than the 2.7/100 PYs reported by Eder et al,7 possibly reflecting the differences in the severity of skin PsO between the studies. Indeed, the median PASI score in participants in our study was 2.4, well within the range of mild disease severity, with only 1 of 19 incident cases (5.3%) having moderate/severe PsO. In contrast, 22% of incident cases in the Toronto cohort had PASI scores greater than 10, indicating moderate or severe PsO.7 In both our study and that of Eder et al,7 the incidence rate was about 10-fold higher than that reported in studies relying on coding of health records alone. There may be potential underrecording from health records for several reasons, including the difficulty of applying the full Classification for Psoriatic Arthritis (CASPAR) criteria without access to certain investigations (eg, radiology), misclassification (eg, fibromyalgia), or, importantly, the presence of milder disease that need not trigger a referral for confirmation of diagnosis. Nonetheless, all 21 incident cases had PsA confirmed by a rheumatologist in a hospital setting, suggesting that our incidence rate represents the full spectrum of PsA found in a primary care setting.
A limitation of our study is the relatively short time of follow-up to allow accrual of sufficiently large numbers of incident cases to assess the importance of risk factors. We were underpowered to investigate known risk factors such as PsO severity,7,8,10 obesity,11 or the presence of nail disease,6 although in the current study, there was a trend for incident cases to have a higher frequency of psoriatic nail disease at baseline. It is also possible that participants in the TUDOR trial may not be fully representative of a primary care PsO population, and although they were not alerted to the primary purpose of the trial (early identification of PsA), there may still be an element of selection bias in favor of the presence of PsA. For instance, the prior presence of musculoskeletal symptoms, other healthcare-seeking behavior, educational background, and socioeconomic and employment status are all examples of factors that may have influenced participation in the trial. Some of these limitations can be overcome with extended follow-up of the TUDOR participants. This is currently underway and should provide a valuable resource for future research.
In conclusion, we have found the incidence of PsA in a prospectively studied primary care population of patients with PsO to be 2.20 per 100 PYs, in line with other studies where the patients have had a full rheumatological assessment. Extended follow-up of the cohort will allow baseline predictors for the development of PsA to be more fully explored.
ACKNOWLEDGMENT
We wish to acknowledge the noncontributing authors of the PROMPT (Early Detection to Improve Outcome in People With Undiagnosed Psoriatic Arthritis) study group who have been responsible for the acquisition of funding and general supervision of the research group: Laura Bjoke, Laura Coates, Emma Dures, Jana James, Vishnu Madhok, Catherine Smith, Eldon Spackman, Andrew Parkinson, and Mel (Brooke) Turfrey.
Footnotes
This report is independent research funded by the National Institute for Health Research (NIHR), Programme Grants for Applied Research (Early Detection to Improve Outcome in Patients With Undiagnosed Psoriatic Arthritis [PROMPT], RP-PG-1212-20007). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
The authors declare no conflicts of interest relevant to this article.
- Accepted for publication July 30, 2024.
- Copyright © 2024 by the Journal of Rheumatology
