Disease-related and psychosocial factors associated with difficult-to-manage and treatment-refractory axial spondyloarthritis: insights from the Greek AxSpA Registry.

Patients with axial spondyloarthritis (AxSpA) with difficult-to-manage (D2M) or treatment-refractory (TR) disease represent an unmet clinical need, but real-world data remain limited. To determine the frequency, demographic, clinical, and psychosocial characteristics of D2M and TR AxSpA patients in a real-world setting, we analyzed data from the Greek AxSpA Registry. D2M disease was defined as Ankylosing Spondylitis Disease Activity Score [ASDAS] ≥ 2.1 despite failure of ≥ 2 biologic (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) with different mechanisms of action. TR was defined as D2M status plus C-reactive protein (CRP) ≥ 0.5 mg/dL after exclusion of infectious causes. D2M, TR, and non-D2M groups were compared and factors associated with D2M status were explored using multivariable regression analysis. Among 395 patients with AxSpA, 40 (10.1%) patients were classified as D2M and 22 (5.6%) as TR. In univariable analysis, higher BASDAI at diagnosis, extra-spinal manifestations (arthritis, dactylitis, enthesitis and psoriasis), BMI ≥ 25 kg/m², current smoking, depression, number of comorbidities, as well as unemployment were associated with the D2M status. In multivariable analysis, unemployment (OR 6.08, 95% CI 1.90-19.46), BASDAI at diagnosis (OR 1.62, 95% CI 1.17-2.24), and depression (OR 2.97, 95% CI 1.04-8.50) remained independently associated with D2M status. Patients with TR AxSpA were characterized by higher BASDAI at diagnosis, more syndesmophytes, and multiple comorbidities. D2M AxSpA is characterized by a more aggressive disease from the outset and throughout, a higher frequency of comorbidities, particularly depression, and an independent association with unemployment. These findings support multidisciplinary management targeting inflammatory burden, modifiable lifestyle factors and psychosocial vulnerability.