Background: Despite numerous treatment options, some axSpA patients do not achieve remission or low disease activity. In 2024 The Assessment of SpondyloArthritis International Society (ASAS) defined Difficult to Manage axSpA (D2M-AxSpA) in 2024 [1].

Objectives: This study was conducted to determine the characteristics of D2M-AxSpA in our biological cohort and the factors that are associated with D2M axSpA at the initiation of b/tsDMARD.

Methods: Patients who applied to the outpatient rheumatology clinic between April 1 and November 30, 2023, with a diagnosis of axSpA and using b/tsDMARD were included in this study. In the cross-sectional evaluation performed during the study period, patients were divided into two groups as D2M and non-D2M axSpA patients based on the ASAS D2M-axSpA definition. Based on the ASAS definition patients were defined D2M-AxSpa when they met: (A)failure of ≥2 b/tsDMARDs (with different mechanisms of action); AND (B) presence of at least one of the following: moderate or more severe disease activity (ASDAS-CRP≥2.1), signs and/or symptoms consistent with active disease (C-reactive protein ≥0.5 or BASDAI ≥4), symptoms affecting quality of life (Health Assessment Questionnaire, HAQ ≥1.2); AND (C) Management of signs and/or symptoms perceived as problematic by the rheumatologist and/or the patient (Physician Global Assessment or Patient Global Assessment VAS ≥50 or Patient Acceptable Symptom State (PASS) negative) Radiographic progression was not included in this assessment as it was not available. Demographic, clinical and treatment data were assessed at the initiation of b/tsDMARD according to D2M status. And comorbidities were assessed for any diagnosis ever made. The factors associated with D2M status on univariate analysis with significance at the 0.20 level were entered into a multivariable model. Backward elimination method was used at a significance of 0.05 level.

Results: A total of 888 axSpA patients on b/tsDMARDs were evaluated. Of these, 13,4% were D2M AxSpa with a mean age of 47,03 (±10,36) years and 63,9% were female. The D2M group had a significantly higher proportion of female patients compared to the group without D2M (63,9% vs %44.0; p<0,001). The D2M group had a significantly higher BASDAI, BASFI and patient VAS global scores at the initiation of b/tsDMARDs. Regarding comorbidities, D2M patients had higher rates of hypertension (32,8% vs 22,4%; p=0.001) and COPD/asthma (17,6% vs 7,2%; p<0,001), with no significant difference in diabetes mellitus and malignancy. When extra-articular involvements were compared, the frequency of psoriasis was significantly higher in the D2M patients than non-D2M patients (19,7% vs 10,4%) p=0,003), and no significant difference was found between the frequency of uveitis and inflammatory bowel disease. Time from diagnosis to first b/tsDMARD start was significantly longer in the non-D2M group (3,23 vs 4,64 p=0,016) (Table 1 ). We incorporated several variables into the multivariable logistic regression analysis, including gender, BMI, age, the presence of diabetes mellitus, psoriasis, HLA-B27 status, current disease duration, the time from diagnosis to first b/tsDMARD start, as well as clinical measures such as BASDAI, BASFI, HAQ VAS Global scores and CRP levels at the time of b/tsDMARD initiation. The final model identified a higher BASDAI score at the start of b/tsDMARD therapy as a significant factor associated with the development of D2M-axSpA. (OR 1.584 (1.156-2.172) p = 0.004 ) (Table 2).

Conclusion: There are nearly 13% of patients determined as D2M in our biological cohort. D2M axSpA was associated with higher disease activity at start of b/DMARD, comorbidities, extra-articular manifestations and female gender. Higher BASDAI score at start of the b/DMARD seems to be an independent factor to predict D2T-AxSpa.

REFERENCES: [1] Poddubnyy D, B.X., Navarro Compán V, Torgutalp M, van der Heijde D., The Assessment of SpondyloArthritis International Society (ASAS) Definition of Difficult-to-Manage Axial Spondyloarthritis [abstract]. Arthritis Rheumatol, 2024. 76 .

D2M AxSpa: difficult-to-manage axial spondyloarthritis; SD: standard deviation; CRP: C-reactive protein; HAQ: Health Assessment Questionnaire; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BASFI: bath ankylosing spondylitis functional index, IBD: inflammatory bowel disease.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.