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

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.

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.