Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER)

Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER): a Cross-sectional Study

Rationale: Psoriasis (PsO) is a common inflammatory skin disease. Besides the skin, it is recognized that this disease can affect multiple domains such as nails, joints and entheses. About 30% of the patients with PsO will develop symptoms in the musculoskeletal domains. Untreated inflammation in psoriatic arthritis (PsA) can lead to irreversible joint damage and further reduces quality of life. Since musculoskeletal involvement is often preceded by the dermatological symptoms of PsO, patients with pure cutaneous psoriasis (PsC) should be routinely screened for joint involvement. Current screening questionnaires, like the often used Psoriasis Epidemiology Screening Tool (PEST), offer a moderate discrimination between patients with PsA and PsC at best. Our aim is to assert the prevalence of known and previously undiagnosed PsA in a PsC cohort. By comparing the gathered data of the PsA and PsC patients, we hope to improve the screening of PsC patients, and to reduce both undertreatment of locomotor symptoms as well as unnecessary diagnostic investigations.

Objective: To ascertain the prevalence of PsA in a tertiary PsO cohort. Secondary objectives will be to ascertain the clinical features of these patients. With these features we want to find clinical, laboratory or genetic markers to predict the presence of PsA in PsO patients. Moreover, we wish to establish the added value of PsA screening for the quality of life (QoL) of PsO patients.

Study design: Multicenter cross-sectional study with a single follow-up visit after 1 year. Patients will be screened at baseline for PsA symptoms by a rheumatology resident and referred to a rheumatology clinic if deemed necessary. At baseline, several clinical and sociodemographic parameters will be assessed. We will collect blood samples for diverse biochemical studies and genomic DNA. Patients will be followed for 1 year after active screening for PsA. Quality of life (QoL) and treatment change will be recorded after this period, to assess the effect of screening and referral.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Psoriasis Vulgaris; Psoriatic Arthritis; Psoriatic Nail
• Intervention / Treatment: Other: cutaneous parameters of psoriasis (exposure); Other: comorbidity (exposure); Other: family history (exposure); Other: lifestyle (exposure); Other: patient reported outcomes (exposure); Other: inflammatory markers (exposure); Other: genetic (exposure)

Detailed Description

This is a monocenter cohort study, which will span at least 1 year from inclusion to follow-up.

A sample of 300 patients known with PsC (cutaneous psoriasis) at the Department of Dermatology of the RadboudUMC, Nijmegen will be included. Inclusion of patients and collection of samples will be performed adjacent to their regular outpatient visits.

During screening, patients will be assessed for signs and symptoms of PsA (psoriatic arthritis). This will include a 68 tender joint count (TJC) and 66 swollen joint count (SJC), a dactylitis count, the Leeds enthesis index (LEI) and a questionnaire screening for inflammatory back pain (IBP).

At baseline visit, different parameters will be noted which can later be used to construct the prediction model. These will include sociodemographic data, relevant comorbidity, family history, characteristics of the PsC, intoxications, and constitutional and specific rheumatological signs and symptoms. During physical examination, the investigators will gather information about body measurements, skin and nail parameters, and rheumatological parameters.

Also, a screening questionnaires already in use (PEST) will be used, as well as a quality of life scores (PsAID12, DLQI, Short-Form 12 Health Survey/SF-12).

Blood will be drawn at baseline to check for different laboratory parameters which are associated with presence of PsA. Both inflammatory markers (e.g. cytokines, chemokines) as markers associated with bone metabolism are of interest. Also, DNA will be gathered via saliva and stored. At a later moment, this will be used to investigate the predictive value of different associated genetic polymorphisms and HLA-associations.

If there is a clinical suspicion of PsA in the clinical exam, the patient will be referred to the Department of Rheumatology of the Sint Maartenskliniek, Nijmegen (SMK). From there on, they will be included in PsA regular care. After 1 year, patient files of the referred patients will be checked to confirm the diagnosis. Also, treatment changes and their effect will be noted. This will include both clinical parameters of the PsA and QoL.

Patients already treated for PsA at a different clinic will not be referred to the SMK. They will be asked for permission to retrieve treatment-related data from their treating physician.

Patients without musculoskeletal involvement will be re-evaluated after 1 year. Again, treatment changes and quality of life will be monitored.

• Study Type: Observational
• Enrollment (Actual): 304

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with cutaneous psoriasis, treated at a third line university outpatient dermatology clinic. Patients will be stratified based on current therapy.

Description

Inclusion Criteria:

• Diagnosis of cutaneous psoriasis
• Age 18 years or above
• Willing and able to comply with visits and study-related procedures
• Provide signed informed consent (IC)

Exclusion Criteria:

• Age below 18 years
• Unable to give IC
• Unable or unwilling to comply with visits and study-related procedures
• Participation in other trials involving PsO

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
topical treatment; 100 consecutive patients with cutaneous psoriasis, stratified on current therapy for cutaneous symptoms: only topical/UV therapy (no systemic therapy)	Other: cutaneous parameters of psoriasis (exposure); characteristic of the cutaneous domains of the psoriasis: age at start, disease duration, current and previous treatment PASI, BSA, nail involvement; Other: comorbidity (exposure); medical and medication history, current and previous comorbidity; Other: family history (exposure); Family history of PsC, PsA, IBD, AS, and uveitis; Other: lifestyle (exposure); Intoxications; Lifestyle: occupation and injuries, sport and physical hobbies; Other: patient reported outcomes (exposure); VAS-score on fatigue, PsC severity, joint pain and general well-being; Other: inflammatory markers (exposure); Measurements of inflammatory and bone remodeling markers in serum and plasma; Other: genetic (exposure); Assessment of known HLA- and SNP-associations with PsA or PsA
systemic treatment; 100 consecutive patients with cutaneous psoriasis, stratified on current therapy for cutaneous symptoms: systemic therapy, but no biologicals. Topical therapy is permitted.	Other: cutaneous parameters of psoriasis (exposure); characteristic of the cutaneous domains of the psoriasis: age at start, disease duration, current and previous treatment PASI, BSA, nail involvement; Other: comorbidity (exposure); medical and medication history, current and previous comorbidity; Other: family history (exposure); Family history of PsC, PsA, IBD, AS, and uveitis; Other: lifestyle (exposure); Intoxications; Lifestyle: occupation and injuries, sport and physical hobbies; Other: patient reported outcomes (exposure); VAS-score on fatigue, PsC severity, joint pain and general well-being; Other: inflammatory markers (exposure); Measurements of inflammatory and bone remodeling markers in serum and plasma; Other: genetic (exposure); Assessment of known HLA- and SNP-associations with PsA or PsA
biologics; 100 consecutive patients with cutaneous psoriasis, stratified on current therapy for cutaneous symptoms: systemic therapy with biologics. Other systemic and topical therapy is permitted.	Other: cutaneous parameters of psoriasis (exposure); characteristic of the cutaneous domains of the psoriasis: age at start, disease duration, current and previous treatment PASI, BSA, nail involvement; Other: comorbidity (exposure); medical and medication history, current and previous comorbidity; Other: family history (exposure); Family history of PsC, PsA, IBD, AS, and uveitis; Other: lifestyle (exposure); Intoxications; Lifestyle: occupation and injuries, sport and physical hobbies; Other: patient reported outcomes (exposure); VAS-score on fatigue, PsC severity, joint pain and general well-being; Other: inflammatory markers (exposure); Measurements of inflammatory and bone remodeling markers in serum and plasma; Other: genetic (exposure); Assessment of known HLA- and SNP-associations with PsA or PsA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of PsA according to CASPAR-criteria	The CASPAR-criteria are positive if a patient has inflammatory enthesitis OR peripheral OR axial arthritis AND cutaneous psoriasis (all of our patients) AND 1 additional outcome (see outcome 2 to 6)	at baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of dactylitis	Dactylitis count, range 0-20, yes/no	at baseline
Absence of rheumatoid factor	A rheumatoid factor measured in serum: U/mL, yes/no below the cutoff point as set by the local lab	at baseline
Presence of new bone formation	X-rays of hand and feet as judged by the local radiologist, presence of new bone formation yes/no	at baseline
Presence of typical psoriatic nail disease	NAPSI	at baseline
Presence of typical psoriatic nail disease	N-NAIL	at baseline
The presence of clinical enthesitis	Leeds Enthesitis Index, scored 0-6	at baseline
The presence of arthritis	66 Swollen Joint Count, 0-66, yes/no	at baseline
The presence of arthralgia	68 Tender Joint Count, 0-66, yes/no	at baseline
The presence of inflammatory back pain	ASAS criteria for inflammatory back pain are positive is there is back pain for more than 3 months, and 4/5 of the following parameters are positive: age of onset <40 year, gradual development, improvement with exercise, no improvement with rest and back pain at night which improves on getting up	at baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comorbidity	Score on Charlson Comorbidity Scale	at baseline
Comorbidity	Score on Functional Comorbidity Index	at baseline
Degree of cutaneous involvement	PASI	at baseline
Degree of cutaneous involvement	Body surface (in percentage)	at baseline
Quality of Life	Short Form 36 scores, DLQI scores, PsAID12 scores	at baseline and after 12 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Sint Maartenskliniek
• Investigators: Principal Investigator: Elke de Jong, Prof MD PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 28, 2022

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Screening; Prediction Model
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Arthritis; Psoriasis; Arthritis, Psoriatic
• Other Study ID Numbers: NL68137.091.18; Nederlands Trial Register (Registry Identifier: NTR7604)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No