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Research project

CSA cohort

Status: Ongoing project

Multicenter, prospective cohort study on identifying diagnostic and prognostic markers in the pre-arthritis phase of arthralgia.

What we do

About our project

The CSA cohort was set up to study patients with clinically suspect arthralgia in order to develop diagnostic/prognostic markers for the development of RA. These are markers of systemic inflammation, and local inflammation, which we measure with imaging (ultrasound and MRI).
The CSA cohort was also set up to improve the mechanistic understanding for progression from clinically suspect arthralgia (CSA) to RA and to determine the physical and psychological well-being of patients with CSA during their disease course.

Our research focus

The development of rheumatoid arthritis (RA) consists of several phases. The phase of arthralgia preceding clinical arthritis is of particular interest because it is hypothesized that disease processes can be effectively modulated during this early phase. This hypothesis is currently being investigated in several proof-of-concept trials. Fundamental to the execution of such trials, and the implementation of positive trial results, is the ability to accurately identify arthralgia patients that will develop RA. With the CSA cohort we aim to identify factors already present in the CSA phase that predict development of RA. We are focusing on systemic biomarkers, imaging markers of local subclinical inflammation, and patient reported outcomes.

Since RA is a systemic disease, inflammation is not only measurable in joints but also systemically. For diagnostic purposes the acute phase reactant C-reactive protein (CRP) is commonly used, but is not specific enough. Many other cytokines and chemokines are increased in RA, and one of the aims of the CSA cohort is to thoroughly evaluate systemic inflammatory markers to identify a set of markers that has a better accuracy to identify patients with imminent RA than the routinely used acute phase reactants. 

Local subclinical inflammation can be detected by Magnetic Resonance Imaging (MRI) and ultrasonography (US). High-quality MRI-studies have revealed that i) of all inflammatory features, MRI-detected tenosynovitis is most predictive, ii) MRI-detected subclinical inflammation does also occur in the general population, especially in certain joints and at older age, and that iii) the accuracy and specificity of MRI in arthralgia considerably increased when using an aged-matched reference population. 
Although MRI has many scientific methodologic advantages, it is scarcely used in clinical practice. Many rheumatologists use US instead, because it is fast, easy applicable, non-invasive, and more feasible and accessible. There is a discrepancy in ultrasound being frequently used in daily rheumatologic practice in CSA, and a lack of scientific evidence on important elements, such as how to define a ‘positive US’, which US markers are most valuable, and how US-results add to other regularly assessed biomarkers. The CSA cohort aims to determine the value of US, also compared to regular MRI (RAMRIS protocol) and novel MRI techniques in the early detection of subclinical inflammation. 

Furthermore, we aim to increase our comprehension of domains that patients perceive as relevant (fatigue, functioning, psychological wellbeing) at presentation with CSA and during follow-up. This will increase our comprehension of time relationships of the development and early progression of fatigue and functional impairments in RA.

Our team

Contact us: CSA@erasmusmc.nl


Annette van der Helm – van Mil, MD PhD

Elise van Mulligen, MSc

Sanne Boeren, MD

Anke Nijs

Irma van Ravesteijn

Ron Buijs