Difficult-to-Manage AxSpA: Global Prevalence and Associated Factors Save

The concept of Difficult-to-Manage (D2M) axial spondyloarthritis (axSpA) is a recent development, with the first expert consensus definition published by the Assessment of SpondyloArthritis International Society (ASAS) earlier this year (1).

The ASAS definition of D2M axSpA encompasses three key criteria: treatment failure, defined as failure of at least two biologic or targeted synthetic DMARDs with different mechanisms of action, in accordance with ASAS-EULAR recommendations, unless contraindicated; suboptimal disease control despite appropriate therapy; and physician or patient acknowledgement of problematic signs/symptoms in patients diagnosed with axSpA by the rheumatologist.

This unified definition has stimulated a wave of new research globally, with multiple studies analysing D2M axSpA in diverse clinical cohorts. These efforts have resulted in numerous abstracts accepted for presentation at EULAR 2025 in Barcelona.

Prevalence

Recent studies have reported the prevalence of D2M axSpA as follows: 8.4% in France (DESIR cohort, 420 patients, Fakih et al., POS#0774), 8.5% in Germany (RABBIT registry, 1850 patients, Proft et al., OP#0098) and in Argentina (Rheuma-Check cohort, Garcia-Salinas et al., 129 patients, POS0919), 10% in the Netherlands (Smits et al., 269 patients, POS0114) and in Canada (Remalante-Rayco et al., 465 patients, POS@0733), 10.1% in Greece (Kougkas et al., 395 patients, POS#0121), 13.4% in Turkiye (Kılıç et al., 888 patients) POS0119), and 41.5% in Spain -using a different definition, however- (Juárez et al., 101 patients, POS#0875). In the USA, using a federated database with 89 contributing healthcare organisations (HCO), including over 125 million patients and including all adult patients diagnosed with AS (ICD-10: M45) between 1953 and 2024, 1.3% of patients were considered as D2M (Magrey et al., 91 493 patients, POS0117).

Associated factors

Common factors associated with D2M axSpA across these studies included: female sex, smoking, comorbidities (obesity, depression, fibromyalgia), non-radiographic form, peripheral involvement, higher disease activity, BASFI, and worse patient-reported outcomes at disease initiation were associated with D2M status.

Future directions

The establishment of the ASAS D2M definition has created a standardised framework for identifying this complex patient subgroup. This will facilitate deeper research into its pathophysiology, epidemiology, and clinical management. Ultimately, it supports the development of targeted clinical guidelines, improved care strategies, and informed resource allocation.

However, to build a truly global understanding of D2M axSpA, data from underrepresented regions such as Africa and parts of Asia remain essential. These areas may present unique challenges related to genetics, comorbidity profiles, and variations in healthcare infrastructure.

1. Poddubnyy D. et al; ASAS. The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis. Ann Rheum Dis. 2025 Apr;84(4):538-546. doi: 10.1016/j.ard.2025.01.035.