Prognostic Markers in Axial Spondyloarthritis

Abstract

Introduction: Axial spondyloarthritis (axSpA) is a heterogenous inflammatory spinal arthritis, with varied features and an uncertain disease course for patients. There are currently few useful blood-based biomarkers to aid in the diagnosis and prognostication of the condition.
Methods: The ‘Prognostic Markers in Axial Spondyloarthritis’ (PROMISE) study explored novel blood-based proteomic biomarkers in the diagnosis of axSpA, assessment of disease activity, treatment response and change in disease over 2 years, through cross-sectional and longitudinal assessment across a range of disease severity.
Results: Alpha 1 anti-trypsin (AAT) and beta 2 microglobulin (β2M) were higher in cases of radiographic Ankylosing Spondylitis than healthy controls (OR 82.3 [95%CI 2.6, 300.3]) and OR 16.2 [95%CI 6.1, 43.6] respectively). β2M was also higher in HLA-B27 positive nr-axSpA compared to healthy controls. Higher AAT was demonstrated in AS cases with acute anterior uveitis (mean AAT previous uveitis 3.3 (SD1.2) vs without uveitis 2.9 (SD1.2), p=0.7). AS patients with greater fatigue had higher levels of macrophage inflammatory protein 1 beta (MIP1β) and vascular endothelial growth factor (VEGF).
Change in β2M over 24 months demonstrated a modest relationship with change in BASDAI in nr-axSpA (mean change BASDAI -0.3 (SD1.6), mean change β2M 0.1μg/ml (SD0.1)). MIP1β levels related to change in BASFI (mean change BASFI -0.3 (SD1.5), mean change MIP1β 16.2pg/ml (SD27.7)). VEGF demonstrated an association with change in BASMI (mean change BASMI 0.2 (SD0.8), mean change VEGF -24.5pg/ml (SD124.0)) and radiographic severity (mean deterioration in mSASSS 1.1 point (SD0.3)). Baseline VEGF correlated inversely with physical activity [95%CI-0.04, -0.005].
Conclusions: A number of biomarkers have been highlighted through this work which could have relevance for more personalised assessment of patients with axSpA. Further validation of these results in a larger cohort over a longer period would enable the detection of greater change in disease and further assessment of these provisional biomarkers of interest.

Date of Award	10 Sept 2025
Original language	English
Awarding Institution	University of Bath
Supervisor	Anita McGrogan (Supervisor), Raj Sengupta (Supervisor) & Neil McHugh (Supervisor)