P70 Exposure to DORIS ≥50% of time and to LLDAS ≥60% of observation time exhibit the best combination of feasibility and protection against adverse outcomes in moderate-to-severe SLE

Objective We assessed the attainment of remission (DORIS) and lupus low disease activity state (LLDAS) in patients with active moderate-to-severe disease and the minimum time dependent exposure associated to lower risk for organ damage accrual and severe disease flares. Thus far, the feasibility of these targets has been validated particularly in unselected SLE cohorts and observational studies, posing a question to their feasibility in difficult to treat patients. Methods This is a retrospective cohort study of SLE patients aged ≥16 years who fulfilled the 2012 Systemic Lupus International Collaborating Clinics (SLICC) and/or 2019 EULAR/American College of Rheumatology (ACR) classification criteria for SLE, that were followed in two Rheumatology centres. Active SLE was defined as Physician Global Assessment≥1.5 and/or SLEDAI-2K≥6, requiring therapy intensification. Screening medical records from the past and forward in time, patients were included from the first occurrence of active disease and data were prospectively collected from subsequent visits. DORIS, LLDAS, organ damage (SLICC/ACR damage index) and flares were monitored. Shared frailty survival and generalized linear models were applied. Results A total 348 patients (92.8% females) were monitored over 60 (27) (median IQR) months with 10 (4) visits per patient and 6.0 (3.0) months between-visit interval. At inclusion, 53.7% of patients had PGA ≥2 (median IQR 2.0 0.5) and 64.7% had clinical SLEDAI-2K (excluding serology) ≥6 (median IQR 6 4), both demonstrative of moderate-high activity/severity. Sustained (≥2 consecutive visits) DORIS and LLDAS occurred in 38.8% and 77.6%, respectively. DORIS and LLDAS led to reduction of subsequent damage accrual (hazard ratio HR:0.64; 95%CI 0.42–0.97 and 0.63;0.46–0.89) and severe flares (HR:0.34;0.22–0.51 and 0.39;0.29–0.51) respectively. Generalized linear models fitting increasing duration of targets, showed that DORIS ≥50% and LLDAS ≥60% of observation time had the best balance between attainability (23.3% and 41.7%) and specificity (85.2% and 73.3%) for damage-free progression (figure 1). Importantly, these targets were also linked to reduced risk for serious adverse events (risk ratio RR:0.56–0.71), hospitalizations (RR:0.70) and mortality (RR:0.06–0.13). Conclusion In moderate-to-severe SLE, remission and LLDAS are feasible goals that protect against multiple disease and patient-related outcomes. Observation time exposure-defined DORIS/LLDAS targets can be useful in treat-to-target strategies and clinical studies.