Treat-to-Target in Systemic Lupus Erythematosus (T2T in SLE)
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. Validation of a low disease activity endpoint for SLE clinical trials and to drive T2T approaches was identified by an international SLE T2T working group in 2015 as an urgent priority.
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 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; 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, one of the primary outcomes of interest; only 14% of the current cohort has accrued organ damage since recruitment at the end of 2-year follow-up period. 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.
Lupus Low Disease Activity State (LLDAS) Study
The first study to be investigated by the APLC is the validation of Lupus Low Disease Activity State (LLDAS). We hypothesise that the attainment of a state of low disease activity is associated with improved outcomes in SLE patients. Defining and validating a state of LLDAS will be a major breakthrough in measuring the effectiveness of treatments and for use in treatment guidelines for SLE.
Undertaking this research project in the Asia Pacific region presents multiple advantages. Firstly, the investigators all have access to large cohorts of SLE patients with longitudinal follow up. Secondly, the high severity of SLE in the Asia Pacific means that comparing the outcomes of patients achieving LLDAS to patients with higher states of disease activity is more feasible. Thirdly, the multiple ethnicities to be studied (including Caucasian, Chinese, Filipino, Malay, Japanese, Taiwanese and Thai) will render the results globally applicable. Finally, inter-ethnic and inter-regional comparisons of SLE phenotypes and outcomes will have important ramifications for regional stakeholders including physicians, governments, and industry.
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