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How are we doing in controlling SLE activity with new drugs? The therapeutic approach to systemic lupus erythematosus (SLE) including lupus nephritis has changed dramatically over the past two decades, shifting from conventional immunosuppression to more effective targeted therapies that aim to reduce both disease activity and glucocorticoid-related damage. 1 Key improvements in clinical trial design are the development of more stringent trial endpoints eg., SLE Responder Index (SRI) , BILAG-based Composite Lupus Assessment (BICLA), prioritizing patient reported outcomes, and validation of DORIS and LLDAS achievement in reducing long-term organ damage and enhancing HrQoL.2 Despite these therapeutic advances, there remains a proportion of ‘non-responders’ as shown in the following response rates across phase 3 SLE trials [Active drug/All patients]: 58%/51% (BLISS-52),3, 43.2%/39.1% (BLISS-76),443%/38% (BLISS-LN),547.8%/39.5% (TULIP-2),650.9%/45.5% (AURORA 2),746.4%/39.9% (REGENCY).8 Nonetheless, the recent American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), Kidney Disease: Improving Global Outcomes (KDIGO) and other guidelines increasingly emphasize the importance of these novel agents in the overall treatment recommendations.How are we doing in controlling SLE activity in the real world? An analysis of data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort demonstrated that 49.2% of 12,236 follow up visits (1652 patients) had active disease, with 46.1% of patients accruing an increase in SLICC/ACR Damage Index (SDI) score >1 during follow up. 9 Data from the Asia Pacific Lupus Collaboration (APLC) patient cohort, comprising a total of 3384 SLE patients followed over 30,313 visits, showed that 24% never achieved lupus low disease activity state (LLDAS) and 25% had episodes of high disease activity status (HDAS).10 The Lupus federated data Network (LupusNet) combines data from five existing SLE registries representing >10,000 patients with SLE from four regions: APLC (Asia Pacific), RELESSER (Europe), FORWARD (North America), and Almenara and GLADEL (Central and South America). Across visits and registries, an average 19% of patients experienced a flare that was captured at a follow-up visit. Interestingly, after inclusion in LupusNet, patients with SLE had stable disease activity during follow-up compared with the time of registry entry.11 Importance of lupus registries and long-term observational studies Lupus varies widely among patients across different races, cultures and regions. Thus, patient registries and real-world data (RWD) in countries and regions provide better insights on how to approach this diversity by:Capturing diverse patient clinical features, treatment outcomes and quality of lifeAssessing treatment effectiveness and safety including organ damageAddressing disparities in care across diverse patient populationsIncorporating social determinants of health, including treatment accessIdentified factors that reflect poorer disease control in the various patient registries are renal and CNS involvement, higher steroid doses, and lower GDP countries. Barriers to disease control also associated with higher mortality include low socioeconomic status, infections, and lack of access to healthcare.What are scientists and the global lupus community doing to improve lupus outcomes? The extreme variability in disease activity within and among individuals requires a highly personalized management approach. Utilizing data from observational cohorts, many centers are now performing trajectory modelling studies to investigate clusters with similar patterns of disease activity in individuals with SLE, and identify factors influencing these patterns in real-world clinical settings. Precision medicine integrates individualized data from various ‘-omics’ levels (like genomics, transcriptomics, proteomics, and metabolomics) to dissect the cellular and molecular pathomechanisms in SLE and identify potential biomarkers that will facilitate the development of stratified treatment recommendations and identify patient subgroups who are likely to benefit from specific treatments. 12 Some initiatives to identify barriers, address disparities, provide solutions and improve lupus outcomes across regions include the Addressing Lupus Pillars for Health Advancement (ALPHA) Project spearheaded by Lupus Foundation of America, which is a global consensus effort to identify, prioritize and address top barriers in lupus which impact diagnosis, care, treatment and research. Similarly, the Lupus Landmark Study – component of Lupus Nexus by Lupus Research Alliance – is a collaborative observational research platform aiming to provide a source of clinical and biological information to accelerate the development of personalized treatments for people living with lupus.Learning Objectives At the end of this presentation participants will be able to:Describe disparities in SLE outcomes based on real-world dataExplain barriers and challenges in achieving SLE disease controlDiscuss current and future strategies to improve SLE outcomesReferences Saegusa K, Tsuchida Y, Komai T, et al. Advances in targeted therapy for systemic lupus erythematosus: Current treatments and novel approaches. Int J Mol Sci. 2025;26(3) doi: 10.3390/ijms26030929Lin A, Wakhlu A, Connelly K. Disease activity assessment in systemic lupus erythematosus. Frontiers in Lupus. 2024;2. doi: 10.3389/flupu.2024.1442013Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31. doi: 10.1016/s0140-6736(10)61354-2Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30. doi: 10.1002/art.30613Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020;383(12):1117–28. doi: 10.1056/NEJMoa2001180Morand EF, Furie R, Tanaka Y, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3):211–21. doi: 10.1056/NEJMoa1912196Saxena A, Ginzler EM, Gibson K, et al. Safety and efficacy of long-term voclosporin treatment for lupus nephritis in the phase 3 aurora 2 clinical trial. Arthritis Rheumatol. 2024;76(1):59–67. doi: 10.1002/art.42657Furie RA, Rovin BH, Garg JP, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N Engl J Med. 2025;392(15):1471–83. doi: 10.1056/NEJMoa2410965Ugarte-Gil MF, Hanly J, Urowitz M, et al. Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the systemic lupus international collaborating clinics (SLICC) inception cohort. Ann Rheum Dis. 2022;81(11):1541–48. doi: 10.1136/ard-2022-222487Kandane-Rathnayake R, Louthrenoo W, Hoi A, et al. ‘Not at target’: prevalence and consequences of inadequate disease control in systemic lupus erythematosus-a multinational observational cohort study. Arthritis Res Ther. 2022;24(1):70. doi: 10.1186/s13075-022-02756-3Zazzetti F, Orillion A, Sbarigia U, et al. Pos1333 From onset to insights: longitudinal assessment of disease activity, flares, and damage accrual in patients with sle across 5 registries in the lupus federated data network (lupusnet). Ann Rheum Dis. 2025;84:1370–72. doi: https://doi.org/10.1016/j.ard.2025.06.682Fasano S, Milone A, Nicoletti GF, et al. Precision medicine in systemic lupus erythematosus. Nat Rev Rheumatol. 2023;19(6):331–42. doi: 10.1038/s41584-023-00948-y