Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical presentation and disease course. Therefore, the development of an instrument to measure SLE disease activity with high validity, reliability, responsiveness to change and feasibility is a major challenge.1 An optimal instrument with these properties should be practical to apply as a primary endpoint in clinical trials and in clinical practice to: assess in individual patients the severity of ongoing disease activity; assess the efficacy of medications and guide management decisions; and identify attainment of treatment targets and new SLE flares. Such an instrument would provide an operational tool to implement treat-to-target management of SLE patients in clinical practice and to optimize the design of clinical trials for new SLE treatments. This presentation aims to report most recent advances in the development of major disease activity measures and treatment target definitions to fulfill these clinical needs.
The SLE Disease Activity Index (SLEDAI), with 24 items, provides a global measure, it is practical to apply and extensively used in clinical practice and trials. However, it presents low sensitivity to change and does not include several important disease manifestations. The British Isles Lupus Assessment Group (BILAG) instrument is an organ-based measure that includes 97 items within nine organ-systems. It is more time-consuming to apply, thus not widely used in clinical practice. The Physician’s Global Assessment (PGA) uses a visual analogue scale for physicians to quantify SLE global activity in a 0–3 range. It is practical to apply, but its reliability is limited, due to a lack of standardisation.
Recognising the limitations of these instruments, composite responder indexes were developed (i.e. SLE Responder Index [SRI] and BILAG-Based Composite Lupus Assessment [BICLA]), by including the SLEDAI, BILAG and PGA, that are used as primary outcome measure in SLE clinical trials.2 However, the SRI and BICLA are not feasible in the clinical setting, and not appropriate to identify flares or treatment targets.
The treatment target for SLE patients is remission or, if that is not achievable, at least low disease activity (LDA), and this target should be maintained over time without flares and with a low dose of prednisone (or stopping them, when possible). Target definitions were developed using the SLEDAI as their basis (e.g., DORIS and LLDAS for remission and LDA, respectively), but require additional items for filling the gaps in the SLEDAI.
The SLE Disease Activity Score (SLE-DAS) is a recently validated 17-item instrument with continuous measurement properties for global SLE activity. It is quick to apply with its online calculator (http://sle-das.eu/). The SLE-DAS presents high accuracy in measuring SLE disease activity, high sensitivity-to-change, as well as higher predictive value for damage accrual as compared to SLEDAI-2K.3 The SLE-DAS provides validated, accurate and easy-to-apply definitions for categories of disease activity, and for the treatment targets of remission and LDA.4–5
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Thanou A, et al. Which outcome measures in SLE clinical trials best reflect medical judgement? Lupus Sci Med 2014;1:e000005.
Jesus D, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis 2019;78(3):365–371.
Jesus D, et al. Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity. Ann Rheum Dis 2021;80:1568–1574.
Assunção H, et al. Definition of Low Disease Activity State based on the SLE-DAS: Derivation and validation in a multicentre real-life cohort. Rheumatology (Oxford). 2021 Dec 3:keab895. doi: 10.1093/rheumatology/keab895. Epub ahead of print. PMID: 34864894.
Explain the optimal properties for disease activity instruments and treatment targets in SLE
Describe the properties of main instruments for measuring SLE disease activity and identifying treatment targets
Demonstrate the ability to assess and interpret the SLE-DAS
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