Background/Purpose: Despite a choice of multiple targeted DMARDs, with different modes of action (MoA), a number of patients with axial spondyloarthritis (axSpA) have failed several treatments. This seems to correspond to a population with specific characteristics that can be termed Difficult to Manage (D2M). A definition of D2M axial spondyloarthritis (D2M-axSpA) has been proposed by the ASAS. Studies using variable definitions estimated a D2M-axSpA prevalence between 10–30%. However, no large cohort study has been conducted based on the ASAS definition. The objective of this study was to determine the prevalence of and factors associated with D2M-axSpA in the DESIR cohort of early inflammatory back pain.

Methods: Patients from the DESIR inception cohort who met the 2009 ASAS criteria for axSpA were included. The baseline characteristics and follow-up data were collected for up to 10 years. Patients were considered to have D2M-axSpA if they failed ≥ 3 bDMARDs and at least one of the sub-criteria making up criterion 2 of the ASAS D2M-axSpA definition (ASDAS ≥ 2.1, signs or symptoms suggestive of active disease, rapid radiographic spinal progression, and reduction in quality of life). This choice reflected limited access to IL-17 inhibitors in this cohort (inclusion in the late 2000s), making it difficult to apply a definition with failure of two different MoA (criterion 1 of the ASAS D2M-axSpA definition). Perception of difficult management (criterion 3) was not assessed. The prevalence of D2M-axSpA was determined, followed by bivariate analysis of the baseline factors associated with the existence of D2M-axSpA. A multivariate analysis using logistic regression was also performed. Quantitative variables were compared using the Mann-Whitney U test and qualitative variables were compared using Fisher’s exact test.

Results: A total of 420 patients were included, mean age of 31.5±7.33 years. A total of 221 (52.6%) patients were women and 368 were HLA-B27 positive (87.62%). The mean follow-up duration was 8.9±2.4 years. The mean ASDAS-crp at inclusion was 2.61±0.98, BASFI was 28.8±22.4, and ASQOL 8.87±5.05. 84 (20%) patients had radiographic sacroiliitis. Fifteen patients (8.4% of bDMARD-treated; 3.6% of all) met the D2M-axSpA definition. D2M-axSpA was associated with female sex and higher ASDAS-CRP, BASFI, and ASQOL at baseline (Table). In a multivariate model adjusted for follow-up duration, only ASQOL at baseline was associated with the occurrence of D2M-axSpA (Odds-ratio 1.28 [1.04-1.63], p=0.03). All included patients met several sub-criteria of the definition, including impairment of the quality of life. None of the patients showed rapid radiographic spinal progression (Figure). A sensitivity analysis showed that seven (1.6%) patients met criteria 1 (failure of ≥ 2 bDMARDs with different MoA) and 2 of the ASAS definition of D2M-axSpA.

Conclusion: The prevalence of D2M-axSpA was low in this cohort of patients with early axSpA, although it was not possible to prescribe a class other than TNF inhibitors during the early years of follow-up. Female sex and high activity, functional, and quality of life scores at baseline were associated with a higher probability of D2M-axSpA, unlike peripheral or extra-musculoskeletal involvement.

Table: Comparison of characteristics between D2M-axSpA and non-D2M-axSpA patients.

Venn diagram of sub-criteria 2 of the D2M-axSpA definition.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-and-baseline-characteristics-associated-with-difficult-to-manage-axial-spondyloarthritis-in-the-desir-cohort/