Commercialization Readiness of Immune Mediator Based Blood Tests that Inform Concurrent and Future Clinical Disease Activity in Systemic Lupus Erythematosus (SLE)

PROJECT SUMMARY/ABSTRACT Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by immune dysregulation, disabling symptoms and progressive organ damage. Recognition and early treatment to prevent tissue and organ damage is challenging, as signs and symptoms of high disease activity and clinical disease flare are captured after their occurrence. Despite clinical instruments of disease activity and improved treatment regimens to temper chronic inflammation, SLE patients may experience an average of 1.8 disease flares annually. Current treatment for ongoing heightened clinical disease activity and disease flares, which must be done in reactive, rather than proactive, fashion, typically relies on rapidly acting, toxic agents such as steroids. Earlier identification and proactive treatment of heightened clinical disease activity and imminent disease flare might prevent significant organ damage and improve the quality of life for patients with SLE. Our scientific premise is that alterations in SLE-associated immune pathways underlie ongoing clinical disease activity and future disease flare. Traditional biomarkers incorporated in clinical disease activity measures, including anti-dsDNA autoantibody and complement components, are not necessarily the earliest, nor sufficient, biologic signals of worsening disease. Using a multi-analyte approach, we leveraged our recently completed SBIR Phase I/II study to determine that lupus patients, prior to disease flare, have additional immune dysregulation of multiple and varied immune pathways. This information was transformed into a Lupus Flare Risk Index (L-FRI) that reflects the pre-flare immune status in lupus patients who go on to flare. Lupus patients with ongoing heightened clinical disease activity are also at risk for permanent organ damage. We therefore leveraged our initial studies to evaluate immune dysregulation in lupus patients with current low disease activity vs. active clinical disease. Again, we observed alterations in multiple and varied immune pathways, but in a different manner than what occurred prior to disease flare. This led us to design a Lupus Disease Activity Index (L-DAI) that correlates well with clinical disease activity measures. Our proposed late stage research in this SBIR SB1 CRP study is to leverage clinically well-characterized, prospectively collected samples from ethnically diverse patient cohorts, including community settings, to validate our algorithms. Aim 1 will focus on validation of our innovative L-FRI in SLE patients during pre-flare vs. nonflare periods based on their future clinical disease activity. Aim 2 will focus on validation of the L-DAI in SLE patients with concurrent low vs. active disease. In addition, we will leverage SBIR SB1 CRP technical assistance funds to develop advanced clinical adoption (Aim 3) and reimbursement (Aim 4) strategies for our L-FRI and L-DAI tests. The L-FRI and L-DAI tests are a game-changer in the lupus space by allowing proactive disease management.