Discordance between systemic lupus erythematosus disease activity index domain weights and their association with organ damage accrual

OBJECTIVE: Studies of damage accrual in patients with systemic lupus erythematosus (SLE) show associations with disease activity measured by the SLE Disease Activity Index 2000 (SLEDAI-2K), but these associations are imperfect. SLEDAI scores are powerfully influenced by weightings (1-8) assigned to each domain. We investigated whether the weightings of SLEDAI-2K domain scores aligned with the risk of organ damage accrual. METHODS: In patients with SLE attending a single center from 2007-2016, disease activity (SLEDAI-2K) and organ damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index; SDI) were recorded prospectively at each visit and annually, respectively. Visits were dichotomized according to whether the visit occurred during a period of damage transition (increase in SDI in the same year). Associations were assessed using Fisher's exact test (univariable analysis) and generalized linear mixed-effect models (multivariable analysis). RESULTS: We analyzed 5,538 visits of 266 patients (86.5% female, 51.5% White). SLEDAI-2K domains positively associated with damage transition all had weights of <4 (odds ratio [95% CI]: pericarditis 5.39 [1.59-18.3] P < 0.01; pleurisy 2.12 [1.14-3.94] P = 0.02; arthritis 1.40 [1.02-1.94] P = 0.04; leukopenia 1.52 [1.04-2.24] P = 0.03). Higher-weighted SLEDAI-2K domains were negatively associated with damage transition, not associated, or were too infrequent to assess. CONCLUSION: Associations of SLEDAI-2K domains with damage accrual were variable and were discordant with domain weightings. Alternative weighting strategies for disease activity instruments could improve their prognostic utility.