RESEARCHERS have found that difficult-to-manage axial spondyloarthritis (D2M-axSpA) affects a small but clinically significant proportion of patients with recent-onset axial spondyloarthritis, carrying a substantial socio-economic burden despite rarely progressing to structural damage or true treatment refractoriness.
D2M-axSpA has recently been defined by the Assessment of Spondyloarthritis International Society (ASAS) and has been reported in 8% to 30% of patients across observational cohorts. However, data on its incidence and long-term outcomes in recent-onset axial spondyloarthritis have remained limited, prompting analysis of the French DESIR inception cohort to address this gap.
This analysis included 177 patients fulfilling ASAS 2009 criteria for axSpA who received at least one biologic disease-modifying antirheumatic drug (bDMARD) over 10 years of follow-up. Patients with D2M-axSpA and treatment-refractory axSpA (TR-axSpA) were classified using both the ASAS definition and an extended definition accounting for historical treatment availability, defined as failure of three or more biologic or targeted synthetic DMARDs regardless of mechanism. Cox proportional hazards models identified baseline factors associated with D2M-axSpA, while clinical, imaging and socio-economic outcomes were assessed longitudinally.
The cumulative incidence of D2M-axSpA was 6.8% (95% CI: 2.4–11.0) under the ASAS definition and 14.4% (95% CI: 8.3–20.2) under the extended definition; TR-axSpA remained rare at 0.7% and 3.7%, respectively. Female sex and higher baseline disease activity were associated with D2M-axSpA development under the extended definition. Patients with D2M-axSpA showed higher fibromyalgia prevalence (60% vs 22.9%), greater cumulative medical visits (110 vs 60) and higher opioid use (100% vs 72%) than other patients.
D2M-axSpA has been shown to be rare and rarely linked to genuine treatment refractoriness or structural progression, yet it continues to impose a persistent disease burden with considerable socio-economic impact. These findings support distinguishing difficult-to-manage from treatment-refractory axial spondyloarthritis in clinical practice and research, and indicate that management should extend beyond repeated treatment escalation to encompass multidimensional approaches addressing symptoms, function and comorbidities such as fibromyalgia.
Reference
Fakih O et al. Incidence, baseline-associated factors and burden of difficult-to-manage axial spondyloarthritis: a 10-year analysis of the DESIR cohort. RMD Open. 2026;12:e007094.
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