Measuring Disease Activity and Outcomes in Early Psoriatic Arthritis

Psoriatic Arthritis (PsA) is a heterogeneous disease, characterized by manifestations of peripheral arthritis, dactylitis, enthesitis, spondylitis, and psoriasis. Patients with PsA experience the impact of disease as loss of functional ability, decreased health-related quality of life (HRQOL) and loss of productivity. Treatment is aimed at preventing these consequences. It is recommended that treatment is given as early as possible, with all manifestations taken into account, and in a treat-to-target strategy. In a treat-to-target strategy, treatment is intensified if a certain target – a composite disease activity measure – has not been achieved. Good measures of disease activity are needed to improve outcomes for patients with PsA. For this purpose, more information is needed on disease activity and outcomes early in the disease course. These are studied in the Dutch southwest Early Psoriatic Arthritis cohoRt (DEPAR) and related sub-studies. This thesis aims to investigate the following four aspects of disease activity and outcomes in early PsA: ultrasound abnormalities of the entheses, burden of disease at time of diagnosis and its relation with disease manifestations, the relation between time to minimal disease activity and outcomes, and the performance of disease activity measures

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers

Objectives: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. Method: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. Results: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002). Conclusions: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volu

Performance of composite measures used in a trial of etanercept and methotrexate as monotherapy or in combination in psoriatic arthritis

Objectives: To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA. Methods: The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS). Results: At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments. Conclusion: PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden. Trail registration: https://ClinicalTrials.gov, number NCT02376790

Achieving sustained minimal disease activity with methotrexate in early interleukin 23-driven early psoriatic arthritis

OBJECTIVES: Methotrexate (MTX) is currently the recommended first-line therapy for treating psoriatic arthritis (PsA), despite lacking clear evidence. No estimates of efficacy of MTX in usual care and no clear MTX responsive clinical or laboratory variables are currently available. This study describes the response to MTX monotherapy in newly diagnosed patients with PsA in usual care. Second, we compared clinical variables and cytokine profiles in patients responding and not responding to MTX monotherapy. METHODS: We used data collected in the Dutch southwest Early Psoriatic Arthritis cohoRt study to select patients with PsA with oligoarthritis or polyarthritis, and at least 1 year follow-up. We analysed disease activity at 6 months of patients who started MTX monotherapy and still used MTX monotherapy 1 year after diagnosis. Cytokine profiles were determined at baseline and after 3 and 6 months with a bead-based multi-immunoassay. RESULTS: We identified 219 patients of which 183 (84%) patients started MTX monotherapy within 6 months after diagnosis. 90 patients used MTX monotherapy throughout the first year of which 44 patients (24%) reached minimal disease activity(MDA) at 6 months, decreasing to 33 patients (18%) after 1 year. Non-responders had significantly higher concentrations of interleukin (IL) 23 and IL-10 before and during MTX therapy. CONCLUSIONS: Our results showed that only 18% of patients with PsA are in sustained MDA after 1 year of MTX monotherapy and non-responders more often had IL-23-driven disease. Our results indicate the need for more treat-to-target and personalised therapy strategies in PsA

Time to minimal disease activity in relation to quality of life, productivity, and radiographic damage 1year after diagnosis in psoriatic arthritis

Background: In a cohort of patients with newly diagnosed psoriatic arthritis (PsA) who received usual care, we investigated the impact of time elapsed to minimal disease activity (MDA) on health-related quality of life (HRQoL), work productivity, and radiographic damage throughout the first year after diagnosis. Methods: Data collected in the Dutch southwest early PsA cohort (DEPAR) study were analyzed. These threemonthly data encompassed disease activity, HRQOL was measured with the Short Form 36 (SF36) Physical Component Scale (SF36-PCS) and Mental Component Scale, and productivity was measured with the Productivity Cost Questionnaire. Radiographic damage was scored at baseline and at 12 months with the PsA-modified Sharp/ van der Heijde score. Patients were classified by time to MDA as in early (within 3 months), late (at 6–12 months), and never MDA in the first year. Results: We included 296 patients who had had their 1-year outpatient visit (mean age 51 years, 53% male). Ninetysix (32%) were classified as early MDA, 78 (26%) as late MDA, and 98 (33%) as never MDA. Data of 24 patients (8%) were missing. SF36-PCS and productivity scores improved after gaining MDA, but remained low in never MDA patients. At 1 year, SF36-PCS and productivity scores were similar in early and late MDA patients. Radiographic progression rate was low and similar in all groups. Conclusion: Gaining MDA was associated with considerable improvement in HRQoL and functioning, irrespective of time to first MDA. In the one third of patients not in MDA in the first year, the disease had a substantial health impact

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers

<p><b>Objectives</b>: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison.</p> <p><b>Method</b>: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI.</p> <p><b>Results</b>: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002).</p> <p><b>Conclusions</b>: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.</p