Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with highly heterogeneous clinical presentation and course. In the last few decades, progress has been slow due to the lack of development of innovative drugs strongly impacting disease management and prognosis [1]. Recently, targeted therapies have been approved with the hope of major impact on these outcomes. However, even in face of such progress, increased mortality remains an unsolved issue, in a disease that mainly affects the young population [2,3].

In 2017 a meta-analysis of studies published between 1950 and 2016 on mortality among adult and pediatric SLE patients highlighted a relevant increase in survival over time throughout the ‘90s, followed by a plateau in the 2000s [4]. A recent Italian population-based study involving more than four thousand SLE patients found a reduction in life expectancy among men and women with SLE of 12 and 22 years, respectively [5]. Similar findings were confirmed in different cohorts across the globe with standardized mortality ratios ranging from 1.7 to 11.1, exemplifying both the current impact of SLE on life expectancy and its diversity among cohorts around the globe [2,[5], [6], [7], [8], [9], [10], [11], [12]].

Even with an increase in life expectancy of SLE patients, permanent organ damage and decreased quality of life are major concerns and, consequently, the main outcomes whose prevention should be the goal in clinical practice.

The development of instruments able to capture disease activity and damage accrual, which could guide clinical decision and aid researchers in clinical studies including trials, has accompanied this history. Disease activity indices have become the scaffold for the assessment of disease response to experimental drugs [13,14], for standardized definitions of flares [15] and, even more, for definitions of disease activity states like remission and low disease activity (LDA) [[16], [17], [18]].

In this review we aim to provide an overview of the most clinically relevant instruments developed to assess disease activity and damage in SLE, provide the scientific evidence validating their use in clinical practice and research, and highlight the advantages and pitfalls of each in the context of a treat to target (T2T) approach.