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

October 15, 2018 updated by: Laure Gossec, Groupe Hospitalier Pitie-Salpetriere

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

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

466

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria
        • Smolen
  • Brazil
      • Porto Alegre, Brazil
        • Palominos
  • Canada
      • Ottawa, Canada
        • Aydin
      • Ottawa, Canada
        • Sibel Aydin
      • Toronto, Canada
        • Eder
  • Estonia
      • Tallinn, Estonia
        • Talli
  • France
      • Clermont-Ferrand, France
        • Soubrier
      • Le Mans, France
        • Dernis
      • Paris, France, 75013
        • Laure Gossec
      • Paris, France
        • Richette
      • Toulouse, France
        • Ruyssen-Witrand
  • Germany
      • Herne, Germany
        • Uta Kiltz
  • Italy
      • Campobasso, Italy
        • Lubrano
      • Roma, Italy
        • Rossana Scrivo
  • Romania
      • Bucarest, Romania
        • Balanescu
  • Russian Federation
      • Saratov, Russian Federation
        • Inna Gaydukova
  • Singapore
      • Singapour, Singapore
        • Katy Leung
  • Spain
      • Barcelona, Spain
        • Juan Canete
  • Turkey
      • Ankara, Turkey
        • Kalyoncu
  • United Kingdom
      • Oxford, United Kingdom
        • Laura Coates
  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Ana- Maria Orbai
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Husni

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Over the 6 months recruitment period, all patients with definite PsA who satisfy the inclusion criteria, seen in outpatient visits in the participating centers by one of the investigators, will be asked to participate. It is planned to take place in 6 participating centres in France, 15 other European tertiary rheumatology centers (Germany, Hungary, Ireland, Italy, Norway, Romania, Spain, Turkey and the UK), 4 centers in the USA, 2 centers in Canada, 1 in Brazil, and 2 in Asia (Singapore and Russia).It is planned that in each center, 15-30 patients will be included. The first 15-30 consecutive patients will be selected in each center to reduce bias selection.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the cutoff value of PsAID corresponding to flare
Time Frame: 6 months

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
To determine the cutoff value of PsAID corresponding to remission
Time Frame: 6 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe Hospitalier Pitie-Salpetriere

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2017

Primary Completion (Actual)

January 30, 2018

Study Completion (Actual)

July 30, 2018

Study Registration Dates

First Submitted

January 4, 2017

First Submitted That Met QC Criteria

April 14, 2017

First Posted (Actual)

April 19, 2017

Study Record Updates

Last Update Posted (Actual)

October 17, 2018

Last Update Submitted That Met QC Criteria

October 15, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ongoing (Other Identifier: Swiss Human Research Portal)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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