OBJECTIVES: In a substantial portion of patients with axial spondyloarthritis (axSpA), disease activity scores remain high despite anti-inflammatory treatment. This is possibly due to factors beyond active inflammation including different pain mechanisms and psychosocial factors. Therefore, our aim was to build a biopsychosocial model to explore the interrelationships of Axial Spondyloarthritis Disease Activity Score (ASDAS) with central sensitization (CS), psychological and lifestyle factors in patients with axSpA. METHODS: Consecutive patients from the prospective Groningen Leeuwarden axSpA (GLAS) cohort were included in this cross-sectional study. Assessments included in the model were educational level, body mass index (BMI), questionnaires on CS, illness perception, pain catastrophizing, coping, anxiety and depression, physical activity (mSQUASH) and ASDAS. Structural equation modelling (SEM), a multivariate analysis testing hypothesized interrelationships between variables, was applied to investigate the effects of CS, psychosocial and lifestyle factors on ASDAS. RESULTS: 332 consecutive axSpA patients were eligible for analyses of which 59% were male, median symptom duration was 21 years, and mean ASDAS was 2.2 ± 0.9. The final SEM model had a satisfactory fit (RMSEA = 0.057 (95% CI 0.45-0.70), CFI = 0.936). Illness perception, CS and BMI had direct, significant, effects on ASDAS. Psychological well-being and educational level were significantly indirectly associated with ASDAS through illness perception. CONCLUSION: Our analyses exploring the interrelationships of biopsychosocial factors related to ASDAS showed that factors beyond inflammation, especially illness perception and CS, seem to contribute significantly to ASDAS in patients treated for axSpA in our standard-of-care cohort, confirming the need for a biopsychosocial approach.