Dynamic disease activity monitoring in Psoriatic Arthritis by novel personalized digital biomarkers*

The level of disease activity in Psoriatic Arthritis determines the actions the
rheumatologist takes to optimise treatment outcome among patients with this
disease. Currently disease activity is measured by a combination of clinical
measures and patients selfreported symptoms and functional ability. This
requires the patients to visit the outpatient clinic on regular intervals.,
which during Covid-19 pandemic was not always possible. The use of
questionnaires to collect Patients Reported Outcome (PRO's) is a feasible
option, the questionnaires fatigue is however a known limiting factor from a
long term perspective. Currently there is no valid alternative for remote
unobtrusive disease activity monitoring. The wide spread use of smart devices
by the general population, such as smartphone or smartwatch, provides
opportunities to develop and study possibilities for Unobtrusive Remote Disease
activity monitoring (URD) using behavioural data captured by the sensors
embedded within the smartphones/smartwatches. We hypothesize that high level of
disease activity in Psoriatic Arthritis (PsA) will lead to lower degree of
physical activity as registered by patients' smartphone as compared to a low
disease activity state. Additionally, digital biomarkers are likely to provide
information on other disease characteristics such as tiredness and sleep
problems. Adding these will enhance discriminative ability of our approach. We
also hypothesize that the information acquired by digital biomarkers will be
comparable to the information received through usage of clinical measures and
PROs. Last but not least, we hypothesize that patient will see the use of
smartphone data as safe privacy-wise and a fair deal in return for lower amount
of follow-up appointments at the out-patient clinic.

To early identify changes in disease activity by changes in digital biomarkers.
Smartphone screen time, keystroke dynamics, accelerometer & gyroscope data,
emoticon use and incidental video recordings will be evaluated on occurring
patterns in relation to clinical disease activity. Parameters will be assessed
in psoriatic arthritis patients and in healthy controls as well. Our working
hypotheses are twofold: 1. Increase in disease activity is preceded by changes
in the above parameters. 2. It is not the absolute value of these parameters
but rather changes in the pattern belonging to an individual that will identify
changes in disease activity. Amendment Index tests (intervention) > measuring
hand function using keystroke dynamics using predefined texts, > evaluating
range of motion using skeletal hand tracking on video using pre-specified hand
gestures > evaluating hand function using a touch-based mobile game reference
test /Comparator: clinical examination by the rheumatologist (swollen joints
and hand function)

An exploratory prospective cohort will be set up.

Prototype Development
The technical prototype development is underway using the previous work by the
AUTH* and FMH# in using artificial intelligence (AI)-based digital biomarkers
in the monitoring of disease activity and progression in Parkinson*s Disease
(www.i-prognosis.eu). A smartphone app is developed to capture accelerometer
and gyroscope data, screen time and key stroke dynamics. In a separate
application patients will be able to assess their joint flexibility capturing
this on video following a prespecified protocol.
Short *test and adjust* cycles will assess the practicalities of the
app-prototype. This will provide a feasible solution to be tested among a
larger sample of patients.

Prototype Testing
The digital biomarker(s) will be tested in daily clinical practice over a
3-month period. Clinical disease activity will be captured by the treating
physicians as part of usual care at start and finish of the 3-month study
interval. As patients are already participating in DEPAR (DEPAR MEC-2012-549)
we aim to use DEPAR data for the purpose of this study. Digital disease
activity will be measured by a smartphone app as described. This will be
accompanied by questions on pain, fatigue, and stiffness (Likert Scale) that
will be generated in a random sequence of 1 to 3 times over a 24-hour period,
taking a few seconds to be answered. The latter will provide us with
information to assess the disease symptoms over time outside the window of the
clinical assessment of disease activity.

Amendment 1: Next to the unobtrusive data capture during daily living the
patients will be asked to perform a few extra tests at the visit in the hospital
Amendment 2: patients with PsA will be asked to participate

Risks There are no health risks associated with participation in this study.
Patients will receive usual care. Burden Patients will be requested to install
an app on their phone that will collect the metadata of the keystrokes,
emoticon use, screen time and the accelerometer & gyroscope data of the phone.
In the app they have full control of the data they want to share. This means
that they could stop data sharing at all times without asking our permission.
To monitor the levels of pain, fatigue and stiffness during the day the app
will also send requests to complete questions on these symptoms. This will be
very short questions that are answerable within a few seconds. These questions
will appear between 1 to 3 times a day. Clinical disease activity will be
monitored each 3 months as described. For most patients this will be a regular
visit to the physician. If they only visit their physician at 6 months or at
longer intervals, they are asked to have an additional 3 month appoint for
clinical disease activity assessment As participants already participate in
DEPAR we will use their DEPAR self-reported measures. If they are diagnosed
less than 12 month ago no additional work is required. If they participate
longer than 12 months they may receive additional questions if we could not
combine the current data collection with their regular DE PAR visit. This will
take about 10 minutes extra per visit. Amendment 1: patients participating in
the hand study will perform the tests on the study phone during the hospital
visit. This will take about 20-30 minutes. Amendment 2: Also none_DEPAR
patients like to participate in the study. They follow normal study procedures,
being clinically examined twice and complete questionnaires twice.