Background/Purpose: The Assessment of SpondyloArthritis international Society (ASAS) group has recently introduced a consensus-based definition for difficult-to-manage (D2M) axial spondyloarthritis (axSpA) to identify patients with active disease despite being treated according to the current standard. This comprehensive definition incorporates not only the number of therapeutic failures but also uncontrolled disease features and the perspectives of both rheumatologists and patients on disease control. However, the real-world frequency of the problem remains unexplored, and little is known about the clinical profiles and factors associated with D2M axSpA. In this study, we aimed to determine the frequency of D2M axSpA and to identify factors associated with D2M disease in a longitudinal clinical cohort.

Methods: This retrospective analysis of a prospective cohort study included patients with a rheumatologist’s diagnosis of axSpA presenting within one year of follow-up (from October 1, 2023 to September 30, 2024) at the Toronto Western Hospital Spondylitis Clinic who received at least 6 months of advanced therapy with a biological and/or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD). Variables were collected at the last follow-up visit. Since MRI was not routinely performed as part of the standard of care, data were unavailable and, therefore, excluded from the definition of “treatment-refractory” disease in this cohort. Sociodemographic and clinical profiles of patients meeting D2M criteria according to the ASAS definition were compared to non-D2M axSpA patients using bivariate analyses. Multivariate logistic regression was used to identify factors associated with D2M.

Results: Among 465 axSpA patients fulfilling the entry criteria, a total of 47 (10.1%) fulfilled all three ASAS D2M criteria. Within the D2M group, 14 (29.8%) had “treatment-refractory” disease, defined as non-response to treatment after excluding fibromyalgia and accounting for elevated CRP levels. Compared to non-D2M, D2M patients had significantly longer symptom duration, higher ASDAS, BASDAI, BASMI, and BASFI, as well as elevated CRP (in approximately 50% of the cases) (Table 1). At the same time, patients in the D2M group were less likely to be employed and had more comorbidities, higher body mass index, as well as a greater prevalence of mechanical back pain and fibromyalgia (Table 1). Logistic regression identified higher BASMI (OR 1.35, 95% CI 1.10 to 1.65, p = 0.004) and fibromyalgia (OR 3.03, 95% CI to 1.01 to 9.05, p = 0.048) as factors significantly associated with meeting D2M criteria (Figure 1).

Conclusion: The results of this study suggest that approximately 10% of patients with axSpA receiving advanced treatment have D2M disease. Half of these patients exhibit objective signs of inflammatory activity, potentially indicating the presence of treatment-refractory disease. In contrast, non-axSpA-related factors (including fibromyalgia, other comorbidities, mechanical issues in the back, and socioeconomic factors) may contribute to the D2M situation in other cases.

Table 1. Bivariate comparison of D2M and non-D2M axSpA patients

Figure 1. Factors associated with D2M in axSpA

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/determinants-of-difficult-to-manage-axial-spondyloarthritis-results-from-a-prospective-cohort-study/