Treat-to-Target in Systemic Lupus Erythematosus (LLDAS Study - Extension Phase)

The convergence of imminent novel therapies for systemic lupus erythematosus (SLE) with the use of treat-to-target (T2T) approaches using validated treatment endpoints heralds a new era in the management of SLE. For this to come to fruition, T2T endpoints are required, that have utility (that is, are feasible and attainable) and validated (that is, are associated with meaningful improvements in outcome). As remission is seldom attained in SLE with currently available therapies, a low disease activity (LDA) treatment target has been deemed more attainable for clinical practice and research. The Asia Pacific Lupus Collaboration (APLC) sets its first research goal to define a low disease activity endpoint for SLE: the Lupus Low Disease Activity State (LLDAS). The APLC has now completed a multicentre prospective validation of LLDAS as a T2T endpoint. This study recruited >1,700 patients from leading centres in nine countries with a median of 2-years of follow-up. Its findings are that LLDAS attainment is associated with significant protection from damage accrual and flare. Notwithstanding the milestone achievement, there remains a great deal of work to be done to refine outcome measures in SLE. The large, multinational APLC cohort is in ongoing follow-up, and new centres in China, Japan, New Zealand, Korea and Taiwan have recently joined. Thus, the APLC now curates the world’s largest contemporary longitudinal registry of SLE patients. With the continuation of the APLC prospective cohort, we intend to achieve longer-term validation (5-year follow-up) of LLDAS. This is to capture more patients with damage accrual, which is the primary outcome of interest; only 14% of the current cohort has accrued organ damage since recruitment. Longer follow-up period will allow us to perform more comprehensive association studies to determine the effects of many exposure variables. In addition, we intend to prospectively validate the remission definitions; develop algorithms to predict organ damage; examine glucocorticoid adverse effects, and support future large-scale biomarker studies and clinical trials.