Investigating the pre-clinical phase of inflammatory arthritis: Risk stratification, imminent disease, and clinical outcomes

Inflammatory arthritis (IA) is the result of a long systemic process made of
successive immune disruptive events occurring in predisposed individuals. To this
date, no recommendation has been outlined for the management of those identified
at-risk of developing IA.
For this purpose, this work first proposed risk scores to stratify individuals identified
as being at risk of developing IA, based on a positive anti-cyclic citrullinated antibody
test and the presence of a new non-specific musculoskeletal pain. In this population,
a simple and practical risk score was designed to assist referral decision making in
primary care settings. It also offered a comprehensive score using multiple
modalities for secondary care use, identifying those at high-risk who would be
suitable for early intervention.
Subsequently, this thesis described the pattern of biomarkers changes occurring in
the at-risk phase of IA using sequential analysis. It highlighted successive changes
from serology and markers of systemic inflammation, followed by markers of local
inflammation. This approach enabled the identification of late-stage biomarker
changes, signalling an imminent transition to clinically apparent IA. These results
may guide clinicians in selecting which biomarkers to monitor more closely. The
identification of an imminent phase may further improve identifying of the best
population to target for intervention.
Analysis of at-risk individuals who developed IA showed the benefits of pre-clinical
observational follow-up compared to conventional care. The results showed shorter
delay between IA specific symptoms and IA diagnosis and a milder disease at
diagnosis, associated with an increased likelihood of achieving early remission.
Understanding the pre-clinical phase of IA improved the identification of those at
high-risk of imminent disease development. Ultimately, it will guide the future
definition and criteria for population recruitment aimed at intervention.