04 Measuring SLE disease activity in 2020: perspectives from clinical research

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical presentation and disease course. It can involve many organ systems with widely diverse clinical patterns in different patients and over time. Furthermore, there are no reliable biomarkers for monitoring the disease course. As a result, measuring SLE disease is highly challenging and there is a lack of user-friendly, sensitive and accurate disease activity measures. This is a top barrier, both for treat-to-target management of SLE patients in clinical practice, as well as in clinical trials for new SLE treatments.^{1 2}

The Physician’s Global Assessment (PGA) is a pragmatic disease activity measure, using a 100 mm visual analogue scale (VAS) for physicians to quantify the patient’s overall disease activity in a 0–3 range. The PGA is sensitive to change, but it requires an experienced physician to use it reliably and consistently in the follow-up of individual patients; furthermore, it has a high interobserver variability. Despite these pitfalls, the PGA is widely applied, including in the composite responder indexes used as primary outcome measure in SLE clinical trials (i.e. SLE Responder Index [SRI] and BILAG-Based Composite Lupus Assessment [BICLA]), the proposed definitions for clinical remission (e.g. DORIS), and low disease activity states (i.e. LLDAS).¹

The SLE Disease Activity Index (SLEDAI), with 24 items, is an extensively used disease activity measure, both in clinical practice and in clinical trials, where it is the driver of clinical response in the SRI. However, SLEDAI presents low sensitivity to change in disease activity – 14.9–47.4% for improvement and 26.2–59.1% for worsening.^{3 4} As a result, usefulness of SLEDAI for guiding treatment decisions in clinical practice is limited. Furthermore, its use for defining responders with the SRI leads to low efficiency of clinical trials.¹

The BILAG is an organ-based instrument that classifies disease activity separately in nine organ-systems and includes 97 items. Due to its high complexity it is not widely used in clinical practice. It is a component of SRI and BICLA. However, it consolidates all features within an organ-system into a single score and thresholds defined for category change impede interpretation. In SRI it is applied only to guarantee specificity of clinical response that is defined by a 4-point decrease in the SLEDAI. The usefulness of BILAG in SRI is unclear, as SLEDAI shows a specificity for change over 90% and in clinical trials few patients improving in SLEDAI presented deterioration in BILAG.^{1 3 4}

The SLE Disease Activity Score (SLE-DAS) is a recently validated 17-item composite index with continuous measurement properties. As compared to SLEDAI-2K, the SLE-DAS presented higher accuracy in measuring SLE disease activity and better sensitivity-to-change, as well as higher predictive value for damage accrual.⁵ Advantages of SLE-DAS include its continuous nature and the inclusion of important disease activity features absent from SLEDAI. Ongoing research suggests that SLE-DAS can accurately define clinical remission, low disease and active disease categories, with a more practical definition compared to other instruments.

Learning Objectives

• Identify unmet needs for measuring SLE disease activity in clinical practice and clinical trials

• Understand the strengths and pitfalls of instruments to measure SLE disease activity

• Apply at each clinical context the most appropriate instrument for measuring disease activity

References

1. Dall’Era M, Bruce IN, Gordon C, et al. Current challenges in the development of new treatments for lupus. Ann Rheum Dis 2019;78(6):729–35.

2. Manzi S, Raymond S, Tse K, et al. Global consensus building and prioritisation of fundamental lupus challenges: the ALPHA project. Lupus Sci Med 2019;6(1):e000342.

3. Jesus D, Rodrigues M, Matos A, et al. Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients. Lupus 2019;28(5):607–12.

4. Yee CS, Farewell VT, Isenberg DA, et al. The use of Systemic Lupus Erythematosus Disease Activity Index-2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients. Rheumatology (Oxford) 2011;50(5):982–8.

5. Jesus D, Matos A, Henriques C, 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):365–71.