Identifying Rheumatoid Arthritis in the preclinical phase

Studies on pathophysiological mechanisms involved in RA evaluate patients with
clinical detectable arthritis. Also in our Leiden Early Arthritis Clinic/
*biobank reumatische ziekten* patients are included when arthritis of recent
onset is present and patients are followed longitudinally. However, recent data
suggest that disease processes can be active years before the development of
clinically detectable arthritis. At present, not much is known on this
preclinical phase. Joint pain of small joints of hands and feet that is of
recent-onset and inflammatory in character is clinically suspect to become RA.
In addition, it is known that an early initiation of treatment is most vital to
improve the outcome of the disease. Early identification of the disease is key
to early treatment initiation. The above mentioned data indicates that the
disease starts perhaps preclinically. Therefore we want to study whether there
is already local inflammation in the preclinical phase.
MRI is the most sensitive method to visualize such inflammation and will
therefore be used in this study.

1) To study whether local inflammation is present in patients with Clinical
Suspect Artralgia and detectable with dedicated extremity MRI
2) To identify determinants (imaging but also serological, genetic factors) for
progression to clinical arthritis

am 3: focus group
1) understanding of perceptions on different theme's from patients with
atralgia of joints from the CSA-cohort by a focus group.
2) understandig if these perceptions are stable over time or if they change
over 1 year.

amendment jan 2017:
Objectives

1) To study whether local inflammation is present in patients with Clinical
Suspect Arthralgia and detectable with dedicated extremity MRI and ultrasound,
and to study the course of subclinical inflammation over time.
2) To identify determinants (imaging but also serological, genetic factors) for
progression to clinical arthritis
3) Evaluate the extent the symptoms influence the physical and mental
well-being.

This study has a longitudinal design, but the majority of the follow-up is
integrated in the already existing Leiden Early Arthritis Clinic/ biobank
reumatische ziekten. Patients with Clinical Suspect Artralgia, identified via
the Early Arthritis Recognition Clinic and via regular referrals, will be
included. Data collected are questionnaires on joint symptoms and life style
factors, a tender joint count, tubes with serum, PBMCs and DNA as well and a
MRI of hand and wrist joints. Patients will be followed by their treating
rheumatologist and research nurse and seen after 4, 13 and 25 months. As such
general patients care will be combined with this observational study. In case
of progression to clinically detectable arthritis, patients are included in the
Early Arthritis Clinic cohort and follow-up in the Inflammatory Artralgia
Cohort stops automatically. Patients in whom after 25 months no arthritis was
detected, will be asked to have one MRI made and follow-up in the light of the
Inflammatory Artralgia cohort will stop since we assume that the chance on
progression later on is low.
The data collected will allow determining whether subclinical inflammation is
preclinically present and if so whether inflammation in RA actually starts in
the synovium (joint lining) or in the bone marrow. Finally it will allow
studies on genetic and serological factors associated with progression to
clinically detectable arthritis.

am 3: 8 patients from the CSA cohort will be asked to participate in the focus
group with meetings on timepoint 0 and after 1 year. These meetings will take
about 2 hour.

Amendment jan 2017, when the participants have an MRI (hand, feet), they also
get an Echo (hand, feet).

Amendment juni 2021: due to logistical/study personnel reason there were no
possiblities to perform an echo. In addition, the MRI scan on baseline will be
performed conform standard care. Follow-up MRIs will be made for research
purposes. The MRI will take about 5 minutes and is without contrast. The study
protocol and PIF have been adjusted for these changes.

The patients that will be followed in this study will be followed by their
rheumatologist for general patient care. So the patients do not have to come to
the hospital specifcally for the present study, but will be seen by their
docter and also a research nurse.
However at baseline some data will be collected that is not part of routint
patient care:
- filling in questionnaire on lifestyle factors
- additional tubes with blood will be taken (additional to general lab ordered
by the rheumatologist)

Patients will have a MRI of hand joints. the MRI on the baseline visit will be
perform conform standard care. Follow-up MRI's will be made for research
purposes.

Blood is generally taken by the rheumatologist, though now additional blood
will be collected.
The MRI is done and is generally safe.

amendment jan 2017, with the MRI also an Echo. The echo takes 20 minutes. There
are no known adverse effects of the echo.

Amendment juni 2021: MRI length is shorter and without contrast. No echo will
be performed. So less impact for the patient.