Remission and Flare in Psoriatic Arthritis: a Prospective 6-month Study With a Double Perspective.

Psoriatic Arthritis Clinical Trial

— ReFlaP  

Official title:

Defining Cut-off Values for Widely-used Composite Scores and Patient-reported Outcome Measures in Psoriatic Arthritis Corresponding to Remission and Flare Assessed by the Physician and the Patient

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03119805
• Other study ID #: ongoing
• Status: Completed
• Start date: May 18, 2017
• Est. completion date: July 30, 2018

Study information

• Verified date: October 2018
• Source: Groupe Hospitalier Pitie-Salpetriere
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to define cut-off values of the most widely used composite scores and patient-reported outcomes, for levels corresponding to remission/low disease activity and for changes in levels corresponding to flares, in PsA, when remission/low disease activity and flare are defined from the patient and physician perspective. The ReFlaP (Remission/Flare in PsA) study is a prospective, multicentric international, longitudinal, observational study.

Description:

Introduction: Psoriatic arthritis (PsA) is a heterogeneous chronic disease with a significant patient-perceived impact leading to pain, fatigue, impaired function and quality of life and psychological distress. Remission is the announced treatment target in PsA. Several definitions of remission have been proposed including definitions on composite scores such as the Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA), however their translation into the patient's perspective is lacking. Flares are frequent in PsA and are important for patients but are not well-defined from the physician's perspective. Although some work is ongoing regarding remission and flare from the patient's perspective, currently no information allows to cross-tabulate and compare the patient and physician perspectives regarding remission and flare in PsA .

The objective is to define cutoffs of the most widely used composite scores and PROs, for levels corresponding to remission/low disease activity and for changes in levels corresponding to flares, in PsA, when remission/low disease activity and flare are defined from the patient and physician perspective.

Methods Design: the ReFlaP (Remission/Flare in PsA) study is a prospective, multicentric international, longitudinal, observational study. It will take place in 2017-18 in 25 centers across Europe, North and South America and Asia. Investigators plan to include a total of 450 patients. The inclusion period will last 6 months; each center will include around 20 patients. Each patient is seen twice at baseline and at 1-6 months (follow-up visit) in the context of usual care.

Patients: Consecutive adult patients with definite PsA (according to ClASsification of Psoriatic ARthritis (CASPAR) criteria and confirmation by a rheumatologist), more than 2 years of disease duration, and will be included after signed informed consent.

Data collection: During each visit, physicians will collect data on the disease and on disease activity: 66 swollen joint counts, 68 tender joint counts, tender entheseal points (Leeds Enthesitis Index) and body surface area of psoriasis. This will allow calculation of most of the usual composite scores of PsA: Arythmetic Mean of Desirability Functions modified (AMDF modified), Disease Activity in PSoriatic Arthritis (DAPSA), clinical DAPSA (c-DAPSA), Minimal Disease Activity (MDA) and Psoriatic Arthritis Disease Activity Score (PASDAS). Well-validated Patient Reported Outcomes will be collected from patients: Patient Global Assessment (PGA), Pain, Health Assessment Quality (HAQ), PSoriatic Arthritis Impact of Disease (PSAID), Psoriatic Arthritis Quality of Life (PsAQoL), 12-Item Short Form Health Survey (SF-12), Patient Acceptable Symptom State (PASS) and Minimal clinically important differences (MCID) as well as the recent Flare questionnaire proposed by GRAPPA. Assessment of disease activity status (i.e. remission or flare) will be performed by both physician and patient using global questions.

Planned analysis

To define cutoffs of the most widely used composite scores and PROs, for levels corresponding to remission/low disease activity and for changes in levels corresponding to flares, in PsA:

From the health professional perspective, the gold standard for 'remission' will be MDA and sensitivity analyses will use physician-perceived remission/low disease activity (single questions) and remission in composite scores (DAPSA, c-DAPSA, modified AMDF, PASDAS); for flare the gold standard will be decision of treatment intensification and sensitivity analyses will use: global assessment of flare and increase in category of disease activity in the composite scores.

From the perspective of the patient, the gold standard will be for 'remission', PASS and as sensitivity analysis, patient-perceived remission/low disease single questions yes/no, and for flares, the GRAPPA flare questionnaire, and as sensitivity analyses, flare according to the patient (single question) and the assessment of worsening in MCID.

Investigators will assess what physician-defined remission/low disease activity/flare and patient-defined remission/low disease activity/flare correspond to both on composite 'physician' scores and on all the collected PRO scores. Investigators will use data collected at baseline cross sectionally for remission/low disease activity and changes in scores between the 2 visits for flares.

Cutoff values for each outcome and for each change in outcome will be calculated using ROC curves and 75th percentile analyses. Sensitivity analyses will explore cutoff values found according to patient demographic characteristics and country. Investigators will compare attainment of remission or flare according to the different definitions, using kappa analyses. Rasch analyses will be used as necessary.

Planned outcomes The expected outcomes of this study are a better knowledge of remission/low disease activity and flare in PsA in accordance to the perspectives of patients and physicians. Investigators will define cutoff values for most widely-used scores in PsA, allowing easier interpretation of study results and in the clinic, helping a better communication with patients.

Better knowledge of the important aspects of disease fluctuation and of patient relevant disease targets in PsA should enhance patient care and management in a treat-to-target approach.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 466
• Est. completion date: July 30, 2018
• Est. primary completion date: January 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age>18 years

• Definite PsA according to the ClASsification of Psoriatic ARthritis (CASPAR) criteria and diagnosis confirmed by a rheumatologist. (Taylor2006)

• Willingness to participate and signed informed consent.

• There are no inclusion criteria based on disease activity or treatment

• Patients with more than 2 years of disease duration will be included in the study for more homogeneity.

Patient will be included consecutively. A registry will be kept locally to note the age and gender of patients who have been proposed the study but refused to participate.

Exclusion Criteria:

• No definite PsA or less than 2 years of disease duration

• Patients who don't speak or read the local language or are not comfortable filling in a paper CRF in the local language.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Locations

Country	Name	City	State
Austria	Smolen	Vienna
Brazil	Palominos	Porto Alegre
Canada	Aydin	Ottawa
Canada	Sibel Aydin	Ottawa
Canada	Eder	Toronto
Estonia	Talli	Tallinn
France	Soubrier	Clermont-Ferrand
France	Dernis	Le Mans
France	Laure Gossec	Paris
France	Richette	Paris
France	Ruyssen-Witrand	Toulouse
Germany	Uta Kiltz	Herne
Italy	Lubrano	Campobasso
Italy	Rossana Scrivo	Roma
Romania	Balanescu	Bucarest
Russian Federation	Inna Gaydukova	Saratov
Singapore	Katy Leung	Singapour
Spain	Juan Canete	Barcelona
Turkey	Kalyoncu	Ankara
United Kingdom	Laura Coates	Oxford
United States	Ana- Maria Orbai	Baltimore	Maryland
United States	Husni	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Hospitalier Pitie-Salpetriere

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Canada,  Estonia,  France,  Germany,  Italy,  Romania,  Russian Federation,  Singapore,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the cutoff value of PsAID corresponding to flare	For flare, the gold standard will be decision of treatment intensification. The primary outcome will be to determine the cutoff value of PsAID corresponding flare.; The PsAID is a questionnaire (paper CRF) that can be used to calculate a score reflecting the impact of psoriatic arthritis (PsA) from the patients' perspective. (Gossec L et al., A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. Ann Rheum Dis. 2014;73(6):1012-9).	6 months
Primary	To determine the cutoff value of PsAID corresponding to remission	For remission, the gold standard will be Minimal Disease Activity. The primary outcome will be to determine the cutoff value of PsAID corresponding to remission. Patients are classified as achieving Minimal Disease Activity if they fulfill 5 of 7 outcome measures: tender joint count =1; swollen joint count =1; psoriasis activity and severity index =1 or body surface area =3; patient pain visual analog scale (VAS) score of =15; patient global disease activity VAS score of =20; Health Assessment Questionnaire (HAQ) score =0.5; and tender entheseal points =1. (L C Coates, J Fransen, P S Helliwell Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment Clinical and epidemiological research Ann Rheum Dis 2010;69:48-53.)	6 months