UCAN CAN-DU: Canada-Netherlands Personalized Medicine Network in Childhood Arthritis and Rheumatic Disease

Childhood arthritis describes a group of diseases that commonly manifest as
pain, stiffness and swelling of the joints and other supporting structures.
Paediatric patients, who are diagnosed with arthritis face symptoms that are
debilitating, can dramatically decrease quality of life and can also extend
beyond childhood into lifelong chronic rheumatic diseases. As such, providing
timely and effective interventions
is crucial for improving short and long term health outcomes for children
living with this disease. Children that are at high-risk of permanent joint
damage due to their arthritis often require advanced therapeutic agents called
biologics. One in three paediatric and adult patients currently receives
biologic therapies for arthritis without any treatment end-date. The latter
resulted in an estimated expenditure of $6.4 billion in the year 2000, which
grew to $33 billion by 2011 within Canada alone. This same scenario was echoed
in the Netherlands, where costs for biologic therapies in RA doubled from 2007
to 2011. Although biologic therapies can dramatically improve disease outcomes,
adverse side effects can be associated with this course of treatment and the
use of these therapies imposes substantial economic burdens on the patients,
their families and society. One of the great strengths of studying diseases in
children is that we can learn about the underlying pathobiology of chronic
inflammation without the influences of aging, varied environmental exposures
and lifestyle choices, which are often confounding factors when studying adult
populations. In addition, the knowledge we gain in the area of immunology from
studying children can be highly relevant and applicable to the adult
populations as well.
Recent work by our team has established that patients and treatment response
can be meaningfully classified using approaches that integrate comprehensive
biologic and clinical data.
Our network research program, UCAN CAN-DU, will have a multi-pronged approach
with a focus on the development of new concepts for standardized evaluation of
disease activity outcomes, novel eHealth based patient-reported outcomes and
the real-time integration of individual biological profiles. The latter will
enable us to learn from every child and family - we will inform practice while
caring for children and accelerating transformative care.

This non-interventional, observational cohort study, aims to standardize the
assessment of disease activity in all JIA patients and correlate this to
systematically acquired clinical, environmental and laboratory derived data.
Ultimately, these data will be used to transform the current step-up treatment
approach of JIA into a more personalised treatment approach. This goal requires
the creation of a large, multicentre, bi-national collaborative network,
including all (academic) paediatric rheumatology expertise centres in the
Netherlands and Canada. UCAN CAN DU will set the logistic and technical
prerequisites to create a sustainable network driven by patient reported
outcome measures.
One of the challenges when it comes to treating childhood arthritis is
providing the correct treatment at the opportune time. While advanced biologic
therapies are frequently used and can be highly effective, we are currently
unable to accurately predict which children should start biologic therapies and
which can discontinue treatment without having disease flares. The overarching
goal of the UCAN CAN-DU study is to address this gap in treatment approaches
and support translational research for all children with juvenile arthritis. We
propose to combine multiple data types - transcriptomic, proteomic (cytokine,
chemokine, matrikine, S100 proteins, and autoantibodies), immunomic and
clinical data - to identify biomarkers that can provide diagnostic and
prognostic information to caregivers at the bedside. We will develop a profile
of biomarkers to predict treatment response and a separate set of biomarkers to
predict risk of relapse.
Our work will be informed by the continued development of our preliminary
disease taxonomy for juvenile idiopathic arthritis (JIA).

UCAN CAN-DU is a multicentre longitudinal observational cohort study that will
use prospective population data of children with JIA. Biologic samples and
clinical data will be prospectively collected at participating centres. All
clinical, biological and patient-derived data will be collected at an
aggregation point. A metadata-architect will install two-way real-time data
syncing channel with databases and apps connected to the aggregation point. The
standard based formats and vocabularies used to store data will also allow
integration with various third party systems. This will enable us to share and
integrate data in real-time into analytic models throughout the study course;
hence providing a continuous real-time feedback from bench to bedside and vice
versa.
The analysis of this prospective cohort will help define and confirm the
biologic pathways predictive of treatment response and disease remission. This
knowledge will then be used to develop a comprehensive clinical predictive tool
to guide effective and safe treatment of childhood arthritis.

We do not anticipate any adverse effects from the study. Venipuncture from
blood collection can be associated with some discomfort, and could include
bruising, bleeding or fatigue. We will offer the participants a localized
numbing cream or anesthetic patches to limit discomfort when possible.

No other adverse consequences are anticipated.