Derivation and validation of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) severe disease activity category: post-hoc analysis of the anifrolumab clinical trials in active systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) or lupus is a chronic, systemic autoimmune disease that occurs when patient’s immune system attacks his or her own tissues and organs. The estimated prevalence of SLE ranges from 48 to 366.6 cases per 100.000 individuals. Inflammation caused by lupus can virtually affect any organ of the body. SLE patients present with variable clinical manifestations ranging from mild skin disease to catastrophic organ failure.
The assessment of disease activity in lupus patients has a central role in clinical practice and trials. During the last decades, multiple disease monitoring instruments have been developed, all presenting important limitations. Recently, our research group derived and validated a new instrument for measuring global lupus disease activity as a continuous score, the SLE Disease Activity Score (SLE-DAS). The SLE-DAS showed higher accuracy in measuring SLE disease activity, better sensitivity-to-change, and higher predictive value for damage accrual, as compared to the currently most used disease activity instrument, the SLE Disease Activity Index 2000 (SLEDAI-2K). The SLE-DAS definitions for classifying remission, low disease activity (LDA), mild, and moderate-to-severe disease activity also presented very high performance. However, the SLE-DAS cut-off for severe disease activity has not yet been derived and validated.
Our intent is to derive and validate the SLE-DAS cut-off for severe disease activity category. We will perform a post-hoc analysis of the aggregated data from the anifrolumab trials in moderate-to-severe SLE. Anifrolumab is a human monoclonal antibody to type 1 interferon receptor subunit 1 approved for the treatment of SLE. These trials will provide a large convenience sample of high-quality prospective data that includes all the measures needed to retrospectively calculate the SLE-DAS and achieve the study aim. The definition of the SLE-DAS cut-off for severe disease activity will represent the value of SLE-DAS above which there is a major organ-threatening or life-threatening disease, and will facilitate the identification of patients requiring more intensive treatment regimens in the clinical setting and the selection of candidates for lupus clinical trials.