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

• ClinicalTrials.gov Identifier: NCT03119805
• Recruitment Status: Completed
• First Posted: April 19, 2017
• Last Update Posted: October 17, 2018
• Sponsor: Groupe Hospitalier Pitie-Salpetriere
• Information provided by (Responsible Party): Laure Gossec, Groupe Hospitalier Pitie-Salpetriere

Study Description

Brief 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.

Condition or disease
Psoriatic Arthritis

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 Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 466 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 6 Months
• 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
• Actual Study Start Date: May 18, 2017
• Actual Primary Completion Date: January 30, 2018
• Actual Study Completion Date: July 30, 2018

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. 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).

2. 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.)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

Locations

United States, Maryland

Ana- Maria Orbai

Baltimore, Maryland, United States, 21218

United States, Ohio

Husni

Cleveland, Ohio, United States, 44195

Austria

Smolen

Vienna, Austria

Brazil

Palominos

Porto Alegre, Brazil

Canada

Aydin

Ottawa, Canada

Sibel Aydin

Ottawa, Canada

Eder

Toronto, Canada

Estonia

Talli

Tallinn, Estonia

France

Soubrier

Clermont-Ferrand, France

Dernis

Le Mans, France

Laure Gossec

Paris, France, 75013

Richette

Paris, France

Ruyssen-Witrand

Toulouse, France

Germany

Uta Kiltz

Herne, Germany

Italy

Lubrano

Campobasso, Italy

Rossana Scrivo

Roma, Italy

Romania

Balanescu

Bucarest, Romania

Russian Federation

Inna Gaydukova

Saratov, Russian Federation

Singapore

Katy Leung

Singapour, Singapore

Spain

Juan Canete

Barcelona, Spain

Turkey

Kalyoncu

Ankara, Turkey

United Kingdom

Laura Coates

Oxford, United Kingdom

Sponsors and Collaborators

Groupe Hospitalier Pitie-Salpetriere

  Study Documents (Full-Text)

Documents provided by Laure Gossec, Groupe Hospitalier Pitie-Salpetriere:

Study Protocol and Statistical Analysis Plan  [PDF] April 21, 2017

More Information

Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lucasson F, Kiltz U, Kalyoncu U, Leung YY, Palominos P, Canete JD, Scrivo R, Balanescu A, Dernis E, Meisalu S, Ryussen-Witrand A, Soubrier M, Aydin SZ, Eder L, Gaydukova I, Lubrano E, Richette P, Husni E, Coates LC, de Wit M, Smolen JS, Orbai AM, Gossec L. Disparities in healthcare in psoriatic arthritis: an analysis of 439 patients from 13 countries. RMD Open. 2022 May;8(1):e002031. doi: 10.1136/rmdopen-2021-002031. Erratum In: RMD Open. 2022 May;8(1):

Coates LC, Robinson DE, Orbai AM, Kiltz U, Leung YY, Palominos P, Canete JD, Scrivo R, Balanescu A, Dernis E, Meisalu S, Ruyssen-Witrand A, Eder L, de Wit M, Smolen JS, Lubrano E, Gossec L. What influences patients' opinion of remission and low disease activity in psoriatic arthritis? Principal component analysis of an international study. Rheumatology (Oxford). 2021 Nov 3;60(11):5292-5299. doi: 10.1093/rheumatology/keab220.

Orbai AM, Perin J, Gorlier C, Coates LC, Kiltz U, Leung YY, Palominos PE, Canete JD, Scrivo R, Balanescu A, Dernis E, Talli S, Ruyssen-Witrand A, Soubrier M, Aydin S, Eder L, Gaydukova I, Lubrano E, Kalyoncu U, Richette P, Husni ME, Smolen JS, de Wit M, Gossec L. Determinants of Patient-Reported Psoriatic Arthritis Impact of Disease: An Analysis of the Association With Sex in 458 Patients From Fourteen Countries. Arthritis Care Res (Hoboken). 2020 Dec;72(12):1772-1779. doi: 10.1002/acr.24090.

Gorlier C, Orbai AM, Puyraimond-Zemmour D, Coates LC, Kiltz U, Leung YY, Palominos P, Canete JD, Scrivo R, Balanescu A, Dernis E, Talli S, Ruyssen-Witrand A, Soubrier M, Aydin SZ, Eder L, Gaydukova I, Lubrano E, Kalyoncu U, Richette P, Husni ME, de Wit M, Smolen JS, Gossec L. Comparing patient-perceived and physician-perceived remission and low disease activity in psoriatic arthritis: an analysis of 410 patients from 14 countries. Ann Rheum Dis. 2019 Feb;78(2):201-208. doi: 10.1136/annrheumdis-2018-214140. Epub 2018 Nov 15.

• Responsible Party: Laure Gossec, Professor, Groupe Hospitalier Pitie-Salpetriere
• ClinicalTrials.gov Identifier: NCT03119805
• Other Study ID Numbers: ongoing
• First Posted: April 19, 2017
• Last Update Posted: October 17, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Laure Gossec, Groupe Hospitalier Pitie-Salpetriere:

composite scores; patient reported outcomes; patient perpective; physician perspective; cut-off values; flare; remission; minimal disease activity; low disease activity

Additional relevant MeSH terms:

Arthritis; Arthritis, Psoriatic; Joint Diseases; Musculoskeletal Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases