Impairment in work and activities of daily life in patients with psoriasis: results of the prospective BioCAPTURE registry.

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors.Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations.Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning.Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

Development of a New Referral Tool to Identify Psoriasis Patients with Concomitant Psoriatic Arthritis: Results of the Prospective DAPPER Cohort.

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to joint damage. While screening questionnaires have been developed, their performance varies. The objective of this study was to develop a referral tool for dermatologists to identify psoriasis patients with concomitant psoriatic arthritis for rheumatological referral. This study used data from the DAPPER study, in which psoriasis patients were screened by a rheumatologist for the presence of concomitant psoriatic arthritis. Multivariable regression analysis was used to identify predictive variables for the presence of concomitant psoriatic arthritis: treatment history with conventional systemic drugs (odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.01-8.74, p = 0.04), treatment history with biologicals/small molecule inhibitors (OR 2.90, 95% CI 1.52-5.53, p = 0.01), patient-reported history of joint pain not caused by trauma (OR 4.23, 95% CI 1.21-14.79, p = 0.01), patient-reported history of swollen joints (OR 4.25, 95% CI 2.17-8.32, p < 0.001), and patient-reported history of sausage-like swollen digits (OR 2.38, 95% CI 1.25-4.55, p = 0.01). Based on these variables, a referral tool was created with an area under the curve of 0.82. This referral tool could be used to aid dermatologists to identify psoriasis patients with concomitant psoriatic arthritis, who may benefit from rheumatological referral.

Determinants of work and social participation in patients with psoriatic arthritis in the Netherlands: an observational study.

BACKGROUND: Psoriatic arthritis can cause pain, disability, and permanent joint damage. This can lead to impairments in work and social participation. Little is known about the extent of these impairments in routine practice. With this study, we aim to examine the extent of work and activity impairment in (subgroups of) Dutch patients with psoriatic arthritis (PsA), and to examine determinants associated with this impairment. METHODS: This is an observational study using data collected from the electronic health records of PsA patients treated at the Sint Maartenskliniek, the Netherlands. Data about work and activity impairment were collected via the Work Productivity and Activity Impairment questionnaire. To compare our PsA-cohort with the Dutch general population, we used age- and sex-matched data derived from the Central Bureau of Statistics. Regression analyses were performed to examine determinants of work and activity impairment. RESULTS: In total, 246 patients were included, of which 126 (51.2%) were female. Mean age (S.D.) was 55.7 (13.2) years. Compared with the Dutch general population, work for pay (WFP) was significantly lower in PsA (52.9% versus 62.6%, P < 0.001). In PsA, younger age and better physical function were associated with WFP status (P < 0.05). Higher disease activity, worse physical function, and worse mental health-related quality of life were associated with both more work and activity impairment (P < 0.05). Furthermore, reaching low disease activity status (LDA) according to Psoriatic ArthritiS Disease Activity Score (PASDAS; ≤ 3.2) was associated with less work and activity impairment than reaching LDA according to DAS28-CRP (≤ 2.9) (P < 0.05). CONCLUSIONS: In PsA patients, worse physical function was associated with a lower likelihood of having WFP, and higher work and activity impairment. PASDAS LDA as a goal for treat to target, compared to DAS28-CRP, appears to favour the reduction of work and activity impairment.

Discovery of Psoriatic Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) Study: A Prospective Observational Cohort.

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to irreversible joint damage. However, a proportion of patients with psoriasis and concomitant psoriatic arthritis remain undiscovered in practice. The aims of this study were: to prospectively determine prevalence, characteristics, and disease burden of psoriatic arthritis in a psoriasis population; and to determine the prevalence and characteristics of patients with active psoriatic arthritis, who were not under rheumatological care. Patients with psoriasis were screened by a rheumatologist at the dermatology outpatient clinic for psoriatic arthritis. Patients with suspected active psoriatic arthritis who were not seeing a rheumatologist were referred to a rheumatologist for confirmation. The total prevalence of psoriatic arthritis in this observational, prospective cohort (n = 303) was 24%. Patients with psoriasis with concomitant psoriatic arthritis had longer duration of skin disease and more often a treatment history with systemic therapies. In this academic, specialized, setting, 2.3% of patients (n = 7), were not receiving rheumatological care despite having active psoriatic arthritis. These patients were characterized by a combination of low (perceived) disease burden and low yield of screening questionnaires, making it difficult for dermatologists to discover psoriatic arthritis in these patients. Thus, screening for more subtle active arthritis in patients with psoriasis in a dermatology setting could be improved.

Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis (COMPLETE-PsA): a double-blind, placebo-controlled, randomised, trial.

BACKGROUND: Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) are the preferred first-line treatment in patients with psoriatic arthritis, although there is a paucity of evidence for the efficacy of conventional synthetic DMARDs and especially their combination. We aimed to investigate whether a combination of methotrexate plus leflunomide is superior to methotrexate monotherapy at improving disease activity in patients with psoriatic arthritis. METHODS: This single centre, investigator-initiated, double-blind, randomised, placebo-controlled trial was conducted at Sint Maartenskliniek in the Netherlands (locations included Boxmeer, Geldrop, Woerden, and Nijmegen). Patients aged 16 years or older with a clinical diagnosis of psoriatic arthritis and active disease (defined as two or more swollen joints; dactylitis counting as one swollen joint) were included. Patients were randomly allocated (1:1) and stratified by high disease activity (psoriatic arthritis disease activity score [PASDAS] ≥5·4) to either methotrexate plus leflunomide (combination therapy) or methotrexate plus placebo (monotherapy), using computer-generated stratified variable block randomisation. In both groups, patients received oral methotrexate 15 mg per week for the first 4 weeks and 25 mg per week thereafter combined with two leflunomide 10 mg tablets once per day or two placebo tablets. During the study period, the patients, nurses, researchers, and treating physicians were all masked to treatment allocation. The primary outcome was the difference in mean PASDAS at week 16, adjusted for baseline PASDAS, between the combination and monotherapy groups, assessed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register (NL7404) on Dec 3, 2018. FINDINGS: Between Feb 19, 2019, and March 11, 2021, 82 patients were screened for eligibility. Four patients were ineligible and 78 were enrolled and randomly assigned to either methotrexate plus leflunomide (n=39) or methotrexate plus placebo (n=39). 50 (64%) of 78 patients were male, 28 (36%) were female, and the median age of patients was 55·0 years (IQR 42·0-64·0). Methotrexate plus leflunomide combination therapy was superior to methotrexate monotherapy at week 16 (PASDAS 3·1 [SD 1·4] vs 3·7 [SD 1·3]; treatment difference -0·6, 90% CI -1·0 to -0·1; p=0·025). There were no study deaths. The most frequently occurring adverse events were nausea or vomiting (17 [44%] of 39 patients in the methotrexate plus leflunomide group vs 11 [28%] of 39 in the methotrexate plus placebo group), tiredness (9 [23%] vs 13 [33%]) and elevated alanine aminotransferase (12 [31%] vs 7 [18%]. Generally, the incidence of mostly mild adverse events was higher in the methotrexate plus leflunomide group than in the methotrexate plus placebo group. INTERPRETATION: Methotrexate plus leflunomide combination therapy results in greater improvement in disease activity according to PASDAS in patients with psoriatic arthritis. However, methotrexate plus leflunomide combination therapy is less well tolerated than methotrexate monotherapy. FUNDING: Regional Junior Researcher Grant from the Sint Maartenskliniek.

Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER): Protocol for a Longitudinal Observational Study.

BACKGROUND: One in three patients with psoriasis will develop psoriatic arthritis (PsA). If left untreated, this can lead to pain, impaired function, and irreversible joint damage. Timely recognition and referral to a rheumatologist are therefore key. However, current methods used to screen patients with psoriasis for those who might benefit from referral to a rheumatologist are not performing well enough. OBJECTIVE: The Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) study is designed to determine the prevalence of PsA in a psoriasis population and to find parameters that can be used to develop a new or enhance an existing instrument for a rheumatological referral. METHODS: DAPPER is a longitudinal observational study with a 1-year follow-up. Patients with psoriasis (N=300) who are treated at an outpatient dermatological clinic will be screened extensively for signs and symptoms of PsA by a trained rheumatologist. If there is clinical suspicion of PsA and the patient is not yet treated by a rheumatologist, referral to the Department of Rheumatology will follow for confirmation of the diagnosis and further care. After 1 year, data on changes in quality of life and PsA and psoriasis disease activity will be collected from the referred patients. The screening visit will be used to gather demographical and medical data, which can later be used to develop the aforementioned screening instrument. RESULTS: Inclusion started in June 2019 and finished in June 2021. Follow-up with newly discovered patients with PsA is ongoing. CONCLUSIONS: The DAPPER study is specifically designed to improve the detection of existing PsA in a dermatologic outpatient setting. Although internal validity will be tested, external validity will have to be checked using a second validation cohort. To predict the development of PsA in the future, longitudinal/prospective data collection is required and will be performed in a follow-up study (DAPPER-i). TRIAL REGISTRATION: Dutch Trial Register NTR7604; https://www.trialregister.nl/trial/7397. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31647.

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review.

Twenty to thirty percent of psoriasis (Pso) patients will develop psoriatic arthritis (PsA). Detection of Pso patients that are (at risk for) developing PsA is essential to prevent structural damage. We conducted a systematic search of five bibliographic databases, up to May 2020. We searched for studies assessing markers (clinical, laboratory, genetic) associated with the development or presence of PsA in Pso patients. Study selection and quality assessment of the included studies was performed, followed by a qualitative best evidence synthesis to determine the level of evidence for a marker and its association with concomitant/developing PsA in Pso. Overall, 259 possible markers were identified in 119 studies that met the inclusion criteria. Laboratory markers related to inflammation and bone metabolism reached a strong level of evidence for the association (not prediction) of PsA in Pso. Only CXCL10 showed strong evidence for a positive predictive value for PsA in Pso. The importance of timely detecting PsA in a Pso population, and finding more (bio)markers contributing to early detection, remains high.

Measuring disease activity in psoriatic arthritis: PASDAS implementation in a tightly monitored cohort reveals residual disease burden.

OBJECTIVES: We aimed to investigate the disease activity and overall disease burden of (subgroups of) patients with PsA using the Psoriatic Arthritis Disease Activity Score (PASDAS) in an already tightly monitored cohort. METHODS: This is a cross-sectional study evaluating data from the first visit of 855 PsA patients after implementation of the PASDAS in our tightly monitored cohort [e.g. DAS 28 (DAS28) was provided as an anchor]. Differences in clinical outcomes between subgroups of patients using established cut-offs for disease activity status [i.e. very low (VLDA), low (LDA), moderate (MDA), and high disease activity (HDA)] were examined. RESULTS: Based on the PASDAS, 53.1% of patients were in VLDA/LDA. 29.5% of patients had ≥1 swollen joint, 20.6% had ≥1 enthesitis index point and 3.0% had active dactylitis. Based on DAS28, 77.5% of the patients were in VLDA/LDA. Patients reaching both DAS28 VLDA/LDA status and PASDAS VLDA/LDA status [N = 445 (52.0%)] were compared with patients reaching only DAS28 VLDA/LDA status [N = 218 (25.5%)]. For these latter patients, significantly worse scores on separate parameters were found in measures used for PASDAS/DAS28 calculation (e.g. swollen and tender joint count and patient's visual analogue scale global disease activity) as well as other disease measures (e.g. function and inflammatory back pain). This result remained, even when the stricter VLDA cut-off was used for the DAS28. CONCLUSION: PASDAS implementation uncovered relevant residual disease activity in a quarter of patients previously assessed as being in DAS28 VLDA/LDA, underscoring the potential value of PASDAS measurements in PsA clinical care.

The Skin May Clear But the Arthritis Won't Disappear: Focusing on Concomitant and New-Onset Psoriatic Arthritis in a Daily Practice Cohort of Psoriasis Patients on Biologic Therapy.

BACKGROUND: Previously identified risk factors for psoriatic arthritis (PsA); nail dystrophy and scalp lesions are highly prevalent in patients with moderate-to-severe psoriasis. Therefore, these variables may not be useful as predictors for PsA in this population. OBJECTIVE: We assessed the predictive value of demographic and clinical characteristics for development of PsA in a cohort of patients with moderate-to-severe psoriasis, currently treated with biologics. Furthermore, we reported the incidence of new-onset PsA in this population and described the characteristics of patients that developed PsA during biologic treatment. METHODS: Demographics and treatment characteristics of psoriasis patients currently using biologic therapy were extracted from the BioCAPTURE database (n=427). Poisson regression was used to calculate incidence rates. Multivariable logistic regression was performed to identify factors independently associated with PsA onset. Patient and treatment characteristics of patients that developed PsA during biologic treatment were described. RESULTS: The incidence of PsA was 1.0 (95% CI 0.8-1.2) per 100 psoriasis-years. Except for a lower risk for PsA in male gender (OR 0.58, 95% CI 0.34-0.98, p-value 0.04), no clinical factors were significantly associated with an altered risk of developing PsA. During biologic therapy, 32 patients (9.4%) newly developed PsA. In this group, 53.8% had PASI<5 at PsA diagnosis. The incidence rate of PsA was 1.6 (95% CI 1.1-2.2) per 100 years on biologic therapy. CONCLUSION: Clinical risk factors might be inaccurate to predict PsA onset in patients with moderate-to-severe psoriasis on biologics. Even with low disease activity, psoriasis patients on biologics are still prone to develop PsA.