POS0258 Predictive value of severe symptoms for residual disease after transitioning from high to low disease activity in axial spondyloarthritis

Background: In clinical practice, a considerable proportion of patients with axial spondyloarthritis (axSpA) continue to experience clinically relevant signs and symptoms even after achieving inactive disease (ID; defined as an Axial Spondyloarthritis Disease Activity Score [ASDAS] <1.3) or low disease activity (LDA; ASDAS <2.1), a phenomenon known as ‘residual disease' [1]. It is plausible that certain predictors of residual disease might already be present before the patient achieves ID/LDA. We hypothesised that the severity of symptoms experienced when in a high disease activity (HDA; ASDAS ≥2.1) state may influence certain biological and psychological disease processes, and therefore be a predictive factor for the presence of residual disease when in an ID/LDA state.
Objectives: To investigate in axSpA the impact of severe symptoms when in an HDA state on the presence of residual disease after achieving ID/LDA.
Methods:
This prospective cohort study used data from the web-based monitoring system SpA-Net, a Dutch multicentre clinical practice SpA registry. Patients with a clinical diagnosis of axSpA who had a consecutive HDA and ID/LDA observation (shift from ASDAS ≥2.1 to <2.1) within a time frame of 12 months in the period 2016-2023 were included. The predictor, severe symptoms when in an HDA state, was defined as a score ≥6/10 for either fatigue, back pain and/or physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]). The outcome was the presence of patient-experienced or objective residual disease. Patient-experienced residual disease was defined as the presence of ≥1 patient-experienced indicator of disease activity (fatigue, back pain and/or BASFI ≥4/10), and objective residual disease as the presence of ≥1 objective indicator (elevated C-reactive protein [CRP], active peripheral manifestations [arthritis, enthesitis or dactylitis], active psoriasis, or physician's impression [physician global assessment ≥2/10]). The association between severe symptoms and residual disease was investigated using logistic regression analyses, adjusted for age, sex and education level. Analyses were repeated in two additional contexts: (1) for the individual severe symptoms independently, and (2) in the ID (ASDAS <1.3) and LDA (ASDAS ≥1.3 and <2.1) subgroups separately. Each analysis only included patients with complete data available for all indicators considered.
Results: In total, 157 out of 478 patients in SpA-Net transitioned from an HDA to an ID/LDA state within a 12-month time frame and had complete data available. Of these patients, 68 (43.3%) were female, the mean age was 48.6 (SD 17.0) years, and the mean symptom duration was 19.2 (SD 13.0) years. In total, 124 (79.0%) patients experienced severe symptoms at the HDA time point (predictor). At the ID/LDA time point, the prevalence of patient-experienced residual disease was 71.4% (n=110/154), and the prevalence of objective residual disease was 60.3% (n=47/78) (outcome). Patient-experienced residual disease was present in 11 of 33 (33.3%) patients who had achieved ID, and 99 of 121 (81.8%) patients who had achieved LDA. Objective residual disease was present in 4 of 13 (30.8%) patients who had achieved ID, and 43 of 65 (66.2%) patients who had achieved LDA. Amongst patients with patient-experienced residual disease, multiple patient-experienced indicators of residual disease were often fulfilled simultaneously (Figure 1). Severe symptoms when in an HDA state was associated with patient-experienced residual disease after achieving ID/LDA (OR: 3.82 [95%CI 1.53-9.52]) (Table 1). When the severe symptoms were considered individually, severe fatigue was the only symptom significantly associated with patient-experienced residual disease (OR: 7.51 [95%CI 3.04-18.57]). The association between severe back pain and patient-experienced residual disease was in the same direction, but not statistically significant (OR: 1.76 [95%CI 0.77-4.01]). Analysis with severe limitations in physical function in HDA as an individual predictor was not possible, as all such patients later had patient-experienced residual disease. No associations between severe symptoms when in an HDA state and objective residual disease were observed. For objective residual disease, the (univariable) effect size for the association with severe symptoms was similar in the ID and LDA subgroups. For patient-experienced residual disease, effect size in the ID subgroup could not be calculated (as all patients in an ID state with patient-experienced residual disease previously had severe symptoms), precluding ID/LDA subgroup comparisons.
Conclusion: Severe symptoms when in an HDA state predicts patient-experienced, but not objective, residual disease after achieving ID/LDA. In particular, severe fatigue when in an HDA state was the main predictor of patient-experienced residual disease. These findings may help to better anticipate the disease course in patients with axSpA and guide expectations and treatment strategies.