SP0036 MASTERPLANS – TAILORING SLE FOR THERAPY

Abstract

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is highly heterogeneous in its clinical manifestations and also in its response to specific therapies. Across a number of trials of novel agents, overall response rates are approximately 40-60% and in the past almost 60 years only one drug (belimumab) has been licensed for use in SLE. Current therapy is therefore based on a ‘trial and error” approach frequently involving glucocorticoid co-therapy. Delayed and poor control of inflammation results in organ damage, cardiovascular disease and glucocortocoid toxicity. We established a consortium of academia and industry partners (MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Stratified approaches (MASTERPLANS) with the aim of identifying key endotypes associated with response and low disease activity on particular therapies. Objectives: Our consortium is addressing the hypothesis that strata exist within SLE populations that will enable more targeted use of existing and novel therapeutic agents and improve response rates. Specifically, B-cell related biomarkers including dynamics and function predict responses to mycophenolate mofetil (MMF) and B-cell targeted biologics and interferon signature/pathway dynamics identifies patients with poorer responses to these agents. Methods: Our approach will firstly be to re-analyse data already available from large studies and trials to identify key predictive factors of response. Also, using data from a large UK cohort, the BILAG-Biologics Register, we will assess clinical factors and biomarkers that predict response and low disease activity. Combining results from these studies with that gained from previous studies will enhance our ability to identify endotypes of response. Conclusion: Identifying biomarkers of response will allow better selection of therapy for individual patients. Using the right drug at the right time will improve control of inflammation for patients with SLE and contribute to improving long-term outcomes. Disclosure of Interests: Ian N. Bruce Grant/research support from: Genzyme Sanofi, GlaxoSmithKline, Consultant for: AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono, Speakers bureau: GlaxoSmithKline, UCB Pharma