1452: Clinical and Demographic Characteristics of Treatment-Refractory Axial Spondyloarthritis: Data from the Greek AxSpA Registry

Background/Purpose: Axial spondyloarthritis (AxSpA) is a chronic inflammatory disease that significantly impairs quality of life. Although biologic and targeted synthetic DMARDs (b/tsDMARDs) have improved disease control, a subset of patients remains treatment-refractory (TR), failing to achieve effective control of inflammation despite sequential use of multiple advanced therapies. This TR subgroup forms part of the broader group of difficult-to-manage (D2M) AxSpA patients. ASAS recently proposed a definition for both D2M and TR to guide research into these special populations [1].

Objectives
To describe the demographic and clinical features of treatment-refractory AxSpA patients in Greece and compare them with the non-TR subgroups.

Methods: Data were retrieved from the Greek AxSpA Registry, a prospective cohort (2022–2023) including patients fulfilling the 1984 modified New York criteria for radiographic AxSpA or the 2009 ASAS criteria for non-radiographic AxSpA. Patients were classified into three groups: non-D2M, D2M non-TR, and TR. TR patients met both of the following criteria: (1) inadequate response, defined as ASDAS ≥2.1 despite treatment with ≥2 b/tsDMARDs with different mechanisms, and (2) objective evidence of persistent inflammation (CRP >0.5 mg/dL). Demographics, clinical, radiographic features and comorbidities were compared among groups.

Results: Out of 395 AxSpA patients included in this analysis, 355 (89.9%) were classified as non-D2M and 40 (10.1%) as D2M, among whom 22 (5.6%) patients met criteria for TR disease. There was no significant difference regarding age, gender, disease duration and proportion of radiographic disease among the three groups (Table 1). However, compared to non-D2M patients, TR patients, as well as non-TR D2M patients, exhibited significantly higher BASDAI, ASDAS, BASFI, Global and Pain VAS (p< 0.001 for all), as well as a higher number of comorbidities (p=0.004). However, depression was more frequent in the non-TR D2M group only (p=0.002). Particularly TR patients had significantly more syndesmophytes, more frequent hip involvement, and were more often overweight and current smokers. Finally, in our cohort all TR patients were HLA B27 positive, compared to 57% of non-TR D2M and 78% of non-D2M patients (p=0.026).

Conclusion: Treatment-refractory AxSpA represents a subgroup of D2M patients with severe disease, characterized by persistent inflammation, functional impairment, more advanced structural damage, despite extensive use of advanced therapies, and multiple comorbidities. Early identification and implementation of tailored multidisciplinary care is needed to improve outcomes in this population.

References

1 Poddubnyy D et al. The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis. Ann Rheum Dis. 2025;84(4):538-546

Acknowledgement

The registry on which this study was based received funding from the Greek Rheumatology Society. The authors are grateful to the study participants