The objective and standardized estimation of disease activity has been always a necessity and, at the same time, a challenge in the manage of such a heterogeneous and complex disease as systemic lupus erythematosus (SLE). The use of a validated index has been recommended, not only for clinical research, but also for daily clinical care (1).
But, unfortunately, despite not a few attempts, we are fare away from getting the proper tool, in terms of accuracy, reliability, and change-sensitivity (2). One of the most popular and widely used indexes for this purpose has been Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and its variants (3). Both economy and simplicity are perhaps its more remarkable strengths. But this index doesn’t capture the SLE activity in every situation in a comprehensive way and its change-sensitivity is definitely low. An improvement has been developed, namely SRI-50 (in fact, a responder index) (4), in a try to overcome that weakness, but this variant of SLEDAI has not attracted much attention from the scientific community, having been used only marginally.
The SLE-disease activity score (SLE-DAS) is the result from a cooperative “bi-center” effort to improve SLEDAI, which validation has been recently published (5). Even though the new index takes as starting point the SLEDAI-2k, the changes introduced are indeed substantial. New items (e.g. haemolytic anaemia) were added and the relative weight of neuropsychiatric SLE was reduced, with a total of 17 items, making possible one more comprehensive and balanced assessment of the disease. As distinctive feature of SLE- DAS, the value of several items changes according to the severity. In this sense, four parameters are scored as continuous variables (arthritis, proteinuria, leucopenia and thrombocytopenia). All the items are weighted according to regression coefficients y/or expert criteria. One mathematical formula was derived for SLE-DAS calculation, enough complex as for be necessary to use a calculator.
An internal and external validation procedures were carried out in the derivation and validation cohort respectively, in a prospective way. Using ROC-statistic, the authors demonstrated than SLE-DAS was better than SLEDAI-2k capturing changes of disease activity (defined as ΔPGA≥0.3) in both directions, improvement and worsening, both in the derivation cohort and in the external validation cohort, with a higher discriminative performance (AUC=0.927; 95% CI 0.885-0.969, p<0.0005) for SLE-DAS when comparing to SLEDAI-2K (AUC=0.787;95% CI 0.718-0.857), p<0.0005) detecting a clinically meaningful improvement (5). A variation in SLE-DAS≥1.72 had a higher sensitivity to detect a clinically meaningful change in SLE disease activity compared with a SLEDAI-2K≥4 variation: for improvement (82.1% vs 44.8%, p<0.0005) and for worsening (93.1% vs 46.6%, p<0.0005), with similar specificities (96%–100%). The results were again replicated in the external validation cohort. Interestingly, the authors also demonstrate that disease activity measured with SLE-DAS over time has a higher predictive value for damage accrual than SLEDAI-2K (5).
Further validation steps are been covered (6), specifically defining cut-off values of SLE- DAS for each disease activity category: remission SLE-DAS≤2.08, LDA 2.08<SLE- DAS≤3.77, mild disease activity 3.77<SLE-DAS≤7.64, and moderate/severe disease activity SLE-DAS>7.64. The overall accuracy of these SLE-DAS cut-off values to identify each disease activity state was 96.4%. The agreement between SLE-DAS and physician’s classification was high (k=0.925, p<0.001).
Certain limitations should be consigned in this step of the development of SLE-DAS
A more accurate and perhaps consensus-derived definitions of the items would be desirable. Further validation in wide and independent cohorts, with large number of clinical situations and activity levels, from ethnically diverse populations will be necessary.
To make possible using the index for clinical practice, the building of a calculator for SLE-DAS available on line is in progress.
In summary, SLE-DAS appears as a well-building, validated activity index with a remarkable improvement in change-sensitivity property as compared with its predecessor, the SLEDAI-2k.Taking into account all the above considerations, I can’t see no many reasons, others than being a newcomer, to not use this index both in clinical practice and research on SLE.
References:
- Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN,Cervera R, Doria A, Gordon C, Govoni M, Houssiau F, Jayne D, Kouloumas M, Kuhn A, Larsen JL, Lerstrøm K, Moroni G, Mosca M, Schneider M, Smolen JS, Svenungsson E, Tesar V, Tincani A, Troldborg A, van Vollenhoven R, Wenzel J, Bertsias G, Boumpas DT. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019;78(6):736-745.
- Thanou A, Chakravarty E, James JA, et al. Which outcome measures in SLE clinical trials best reflect medical judgment? Lupus Sci Med 2014;1:e000005.
- Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002;29:288-91
- Touma Z, Urowitz MB, Taghavi-Zadeh S, Ibañez D, Gladman DD. Systemic lupus erythematosus disease activity Index 2000 Responder Index 50: sensitivity to response at 6 and 12 months. Rheumatology (Oxford) 2012;51(10):1814-9.
- Jesus D, Matos A, Henriques C, Zen M, Larosa M, Iaccarino L, Da Silva JAP, Doria A, Inês LS. 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, Matos A, Henriques C, et al. THU0267 The SLE disease activity score (sLE- DAS) enables accurate definitions of SLE remission and LDA as achievable targets in disease management. Annals of the Rheumatic Diseases 2019;78:411-412.
