Lupus (2019) 0, 1–6 journals.sagepub.com/home/lup PAPER Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36–month prospective cohort study of 334 patients D Jesus 1 , M Rodrigues 1 , A Matos 2,3 , C Henriques 2,3,4 , JA Pereira da Silva 1,5 and LS Ineˆs 1,6 1 Rheumatology Department, Centro Hospitalar e Universita´rio de Coimbra, Coimbra, Portugal; 2 School of Technology and Management, Polytechnic Institute of Viseu, Viseu, Portugal; 3 Centre for the Study of Education, Technologies and Health, Viseu, Portugal; 4 Centre for Mathematics, University of Coimbra, Coimbra, Portugal; 5 Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; and 6 Faculty of Health Sciences, University of Beira Interior, Covilha˜, Portugal Objective: The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. Methods: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ÁPGA  0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operat- ing characteristic (ROC) analysis. Results: Adjusted mean PGA and SLEDAI-2K scores pre- sented a high correlation (rho ¼ 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628– 0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K  4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822–0.932), p < 0.0005), with a sensitivity of 35.3%. Conclusions: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research. Lupus (2019) 0, 1–6. Key words: Disease activity index; systemic lupus erythematosus; SLEDAI; SRI Introduction The assessment of disease activity has a central role in clinical daily practice, research and clinical trials involving patients with systemic lupus erythemato- sus (SLE). Multiple disease monitoring instruments have been developed, but all present important limitations. The SLE Disease Activity Index (SLEDAI), a global score index that includes the sum of 24 weighted clinical and laboratory variables, with its SLEDAI-2K and Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)- SLEDAI versions, is the most widely used SLE disease activity measure. 1–3 SLEDAI is used world- wide in daily clinical practice. Moreover, it is the core determinant of the SLE Responder Index (SRI4) used in clinical trials and also to define flares, remission and low disease activity states. 4–7 However, the inability to demonstrate clinically meaningful improvements in recent trials, despite a positive clinical impression of efficacy, has raised the debate about the performance of SLEDAI in detecting clinically meaningful changes in SLE dis- ease activity. 8 Each item of the SLEDAI is scored dichotomically, resulting in the attribution of the same numerical weight, irrespective of the severity of change observed. Additionally, potentially severe lupus manifestations, such as hemolytic anemia, pneumonitis or gastrointestinal activity Correspondence to: Luı´s Sousa Ineˆs, Servic¸o de Reumatologia, Centro Hospitalar e Universita´rio de Coimbra, EPE, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. E-mail: luisines@gmail.com Received 6 November 2018; accepted 18 February 2019 ! The Author(s), 2019. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203319836717