OP0097 Impact of Residual Disease on Disease Flares in Axial Spondyloarthritis: A Longitudinal Study in a Dutch Clinical Practice Registry

Background: In axial spondyloarthritis (axSpA), guidelines recommend aiming for sustained inactive disease (ID, Axial Spondyloarthritis Disease Activity Score [ASDAS] <1.3) or, alternatively, low disease activity (LDA, ASDAS <2.1) [1]. However, even when these targets are met, many patients still experience clinically relevant signs or symptoms of disease, which is considered residual disease [2]. Residual disease may affect patients' daily functioning and may also have prognostic significance as it could influence the course of the disease. Our hypothesis is that the presence of residual disease in axSpA is associated with future disease flare.
Objectives: To assess, in patients with axSpA, whether the presence of residual disease when in an ID/LDA state is associated with the occurrence of disease flares (objective 1) and the time to flare (objective 2) in the subsequent 12 months.
Methods: Data were used from patients with axSpA participating in SpA-Net, a Dutch multicentre web-based monitoring system for SpA in clinical practice. Included patients needed to be in an ID/LDA state (ASDAS<2.1) and have at least one subsequent ASDAS measurement available in the next 12 months. The predictor was objective or patient-experienced residual disease. Objective residual disease was defined as the presence of ≥1 objective indicator (active peripheral manifestations [≥1 swollen joint/enthesitis/dactylitis count], active psoriasis [body surface area >3%], elevated CRP, and/or physician global assessment ≥2/10) while in ID/LDA. Patient-experienced residual disease was based on patient-reported indicators (fatigue, back pain, and/or Bath Ankylosing Spondylitis Functional Index score ≥4/10) while in ID/LDA. The outcome was a disease flare, defined as an ASDAS increase of 0.9 and shift from ID/LDA to a high disease activity state (ASDAS≥2.1). Logistic regression analyses were used to assess the association between residual disease and occurrence of flare (objective 1). Survival analyses (Kaplan-Meier plots, Cox regression analyses) were used to assess the association between residual disease and the time to flare (objective 2), where also in a sensitivity analysis each patient-experienced indicator was considered individually. Separate models were used to assess objective or patient-experienced residual disease as predictor.
Results: In total, 140 patients (mean age 49.9±13.5 years, 55 (39.3%) female) were included, with a mean ASDAS of 1.5 (SD 0.4). At time of ID/LDA, 82 (62.1%) patients had patient-experienced residual disease and 61 (58.7%) had objective residual disease, respectively. During follow-up, 36 patients (25.7%) experienced a flare, after a mean of 200 (SD 104) and median of 178 (IQR 129-288) days, with a mean increase in ASDAS of +1.5 (SD 0.5). In multivariable logistic regression analyses, the presence of patient-experienced residual disease was significantly associated with an increased risk of flare (OR=3.4, 95% CI 1.3–9.2) (Table 1). In the univariable survival analysis, patients with patient-experienced residual disease had a lower probability of remaining flare-free in the subsequent 12 months compared to patients without patient-experienced residual disease (Figure 1). Patient-experienced residual disease was also significantly associated with an increased hazard of flare, and shorter time-to-flare, compared to patients without patient-experienced residual disease in multivariable analysis (HR=3.2, 95% CI 1.3–7.8). When considering each indicator of patient-experienced residual disease individually while in an ID/LDA state, residual fatigue and limitations in physical function were associated with flare (fatigue: HR=2.5 [95% CI 1.2 – 5.1], limitations in physical function: HR=2.3 [95% CI 1.0 – 5.1]), while back pain was not. In contrast, objective residual disease was not associated with the occurrence of disease flares nor with the time-to-flare (Table 1).
Conclusion:
The presence of patient-experienced – but not objective – residual disease when in ID/LDA is associated with the occurrence of disease flare and shorter time to flare in axSpA. These findings suggest that residual symptoms have prognostic relevance in axSpA. Whether treatment of persistent symptoms after achieving treatment targets actually prevents disease flares, and improves short and long-term health outcomes, deserves further study.