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

NCT ID: NCT03119805

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 466 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-05-18
• Study Completion Date: 2018-07-30

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.

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.

Conditions

Psoriatic Arthritis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Groupe Hospitalier Pitie-Salpetriere

OTHER

Sponsor Role: lead

Responsible Party

Laure Gossec

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ana- Maria Orbai

Baltimore, Maryland, United States

Husni

Cleveland, Ohio, United States

Smolen

Vienna, , Austria

Palominos

Porto Alegre, , Brazil

Aydin

Ottawa, , Canada

Sibel Aydin

Ottawa, , Canada

Eder

Toronto, , Canada

Talli

Tallinn, , Estonia

Soubrier

Clermont-Ferrand, , France

Dernis

Le Mans, , France

Laure Gossec

Paris, , France

Richette

Paris, , France

Ruyssen-Witrand

Toulouse, , France

Uta Kiltz

Herne, , Germany

Lubrano

Campobasso, , Italy

Rossana Scrivo

Roma, , Italy

Balanescu

Bucharest, , Romania

Inna Gaydukova

Saratov, , Russia

Katy Leung

Singapore, , Singapore

Juan Canete

Barcelona, , Spain

Kalyoncu

Ankara, , Turkey (Türkiye)

Laura Coates

Oxford, , United Kingdom

Countries

United States; Austria; Brazil; Canada; Estonia; France; Germany; Italy; Romania; Russia; Singapore; Spain; Turkey (Türkiye); United Kingdom

References

Yazji SM, Helliwell PS, Balanescu A, Dernis E, Kiltz U, Kalyoncu U, Leung YY, Orbai AM, Smolen JS, de Wit M, Gossec L, Coates LC. Association Between Patient Perception of Disease Status and Different Components of the Minimal Disease Activity Criteria in Psoriatic Arthritis. J Rheumatol. 2025 Apr 1;52(4):362-367. doi: 10.3899/jrheum.2024-1149.

Reference Type: DERIVED

PMID: 39814446 (View on PubMed)

Leung YY, Eder L, Orbai AM, Coates LC, de Wit M, Smolen JS, Kiltz U, Palominos P, Canete JD, Scrivo R, Balanescu A, Dernis E, Meisalu S, Soubrier M, Kalyoncu U, Gossec L. Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study. RMD Open. 2023 Sep;9(3):e003157. doi: 10.1136/rmdopen-2023-003157.

Reference Type: DERIVED

PMID: 37709527 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35523519 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33751029 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31609525 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30442648 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ongoing

Identifier Type: -

Identifier Source: org_study_id