PO:15:220 | Outcomes of extra renal flares in systemic lupus erythematosus: longitudinal analysis of a monocentric cohort

Marco Oliva¹, Giorgia Capozzo¹, Giancarlo Cascarano¹, Chiara Cardelli¹, Dina Zucchi¹, Angela Elia¹, Elena Elefante², Viola Signorini², Chiara Stagnaro², Chiara Tani¹, Marta Mosca¹. | ¹Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; ²Rheumatology Unit, AOUP, Pisa, Italy.

Background. Lupus low disease activity state (LLDAS) and remission are key therapeutic targets in systemic lupus erythematosus (SLE), associated with better long-term outcomes. This study aimed to evaluate the frequency of LLDAS achievement 12 months after an extra-renal flare and to identify clinical and serological predictors in a monocentric SLE cohort.

Methods. This observational cohort study included SLE patients with an extra-renal disease flare between 2017 and 2024. Patients were assessed at the flare occurrence (T0) then at 3 (T3), 6 (T6), and 12 months (T12). Active organ involvement at flare was categorized based on BILAG domains, and disease activity at T0 and follow-up was evaluated by SLEDAI-2K score. At each time point, the attainment of clinical remission (based on the DORIS definition, excluding the physician global assessment [PGA]) and/or LLDAS-5 (according to modified criteria: excluding the PGA and requiring a prednisone dose < = 5 mg/day) was recorded. Univariate and multivariable logistic regression analysis of potential predictors were performed.

Results. 98 patients were included. Demographic, clinical, and therapeutic characteristics are summarized in Table 1. During the follow-up, SLEDAI-2K score progressively declined from a median of 7 (4-10) to 2 (0-4); at 12 months, 67 (69.0%) patients were in LLDAS5 and 38 (38.7%) were in remission. As shown in figure 1, clinical outcomes assessed at 3, 6, and 12 months demonstrated a gradual increase in the proportion of patients achieving LLDAS5 and clinical remission. Comparison between those who reached LLDAS-5 at T12 and those who did not is detailed in Table 2. Patients not achieving LLDAS-T12 received significantly higher cumulative 6-methylprednisolone doses (2786.2 ± 349.6 mg vs 1740.3 ± 158.8 mg, p = 0.002) and higher daily doses at T12 (7.07 ± 1.38 mg/day vs 2.95 ± 0.24 mg/day, p < 0.001). In univariate analysis, variables associated with the achievement of LLDAS5 at 12 months resulted: SLEDAI-2k score at flare (7.4 ± 5.5, p < 0.005), male sex (93.3% vs. 64.6%, p = 0.027), the presence of anti-dsDNA antibodies at flare (p = 0.014). However, in multivariable logistic regression, only the baseline SLEDAI score remained significantly associated with LLDAS5 at 12 months (OR 0.89, 95% CI 0.82–0.97). An additional key finding is that no specific BILAG domain manifestation was independently associated with the achievement of LLDAS5 at T12; however, hematologic (OR 0.15, p= 0.015) and mucocutaneous involvement (OR 0.29, p= 0.018) were both negatively associated with remission at T12.

Conclusions. This study demonstrated that in real-life setting, achievement of treatment targets with standard of care remains suboptimal, especially in patients with high disease activity, mucocutaneous and hematological manifestations. Interestingly, patients not achieving targets required significantly higher doses of 6-MP, highlighting the importance of early disease control and tailored treatment strategies.