Difficult-to-treat RA: a study to obtain insight into the occurrence and nature of potential problems underlying the disease state and into its clinical burden

Difficult-to-treat rheumatoid arthritis (RA) is defined by signs of
active/progressive RA, which is perceived as problematic by rheumatologist
and/or patient, despite treatment according to European League Against
Rheumatism (EULAR) recommendations and failure of *2 biologic (b-) or targeted
synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs)(with different
mechanism of action. ~5-20% of RA patients can be characterized as
difficult-to-treat. The treatment of difficult-to-treat RA patients may be
challenged by several problems underlying the disease state, e.g. immunologic
mechanisms, adverse drug reactions, treatment non-adherence, and comorbidities.
However, the importance of these individual problems is unknown, which shows
the unmet need for this patient population.

To obtain insight into the occurrence and nature of potential problems
underlying difficult-to-treat RA and into its clinical burden, that will
eventually be used to improve the management approach for difficult-to-treat
RA.

Exploratory, single centre, cross-sectional, observational.

Patients will have one study visit, at which an interview, joint examination
and blood sampling will be performed. In addition, patients are requested to
fill in 11 questionnaires. These can be filled in at home. The total amount of
blood drawn in the study is 5 ml. Patients may develop a hematoma at the site
of venepuncture.
Some parameters (viz., medical history, demographic data, height/weight,
smoking status, alcohol use, disease duration, usage of anti-rheumatic drugs
and painkillers and clinical disease parameters) are recorded or performed in
regular care depending on the clinical situation. In that case the data will be
retrieved from the electronic patient record. However, as regular care does not
follow a strict protocol, these data may not be available for each patient. In
that case, these assessments will be collected specifically for the purpose of
this study.
In patients without evident arthritis but with some suspicion of synovitis,
ultrasound (US) will be performed in regular care in (a) suspect joint(s) to
exclude or demonstrate synovitis. In patients with (a) swollen joint(s) but
with some suspicion of having only secondary osteoarthritis, in these joints
(in addition to ultrasound) an X-ray will be performed in regular care to
exclude or demonstrate secondary osteoarthritis. For both US and X-ray, an
ipsi- or contralateral joint will be chosen as a control joint, these will be
study procedures.
The total study visit (including filling in the questionnaires) will take
approximately 2 hours.

Sub study: Qualitative research about non-adherence to DMARDs
Participants will be invited for a second study visit for a sub study to
explore reasons of DMARD non-adherence. A minimum of 10 patients will be
interviewed face-to-face to find out the reasons of non-adherence for DMARDs
and to examine facilitators and barriers for optimal adherence. These
face-to-face interviews will be carried out until data saturation is reached
during two successive interviews (expected number of interviews in between 10
and 15). The reasons, facilitators and barriers respectively, that have been
discussed during the face-to-face interviews will serve as a base for
conducting the card soring task. They will be reduced to a maximum of 60 for
each category by the project group.
Another 40 patients will be asked to perform a card sorting task to sort the
reasons, facilitators, and barriers, respectively, based on similarity and,
thereafter, to sort these into five categories of applicability to themselves.
20 rheumatologists (in training) will sort these into five categories in terms
of applicability to the general population of patients with RA.