Neuropsychiatric involvement in systemic lupus erythematosus contributes to organ damage beyond the nervous system: a post-hoc analysis of 5 phase III randomized clinical trials

Abstract

Objective To investigate the association between neuropsychiatric systemic lupus erythematosus (NPSLE) and SLICC/ACR damage index (SDI) items, especially non-neuropsychiatric items. Methods Baseline data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) were analysed. NPSLE involvement was defined as NP BILAG A/B/C/D (n = 272); NP BILAG E denoted non-neuropsychiatric SLE (n = 3273). We employed multivariable logistic regression analysis adjusting for age, sex, disease duration, and ethnicity. Results The median (IQR) and mean ± SD SDI scores were 0 (0–1) and 0.62 ± 1.09. Compared with the non-neuropsychiatric SLE group, NPSLE patients were more likely to develop damage (adjusted (a)OR = 2.86; 95% CI = 2.28–3.59). This held true also after suppression of the NP SDI items (aOR = 1.70; 95% CI = 1.36–2.12). Beyond the neuropsychiatric domain, NPSLE was associated with damage in the cardiovascular (aOR = 2.63; 95% CI = 1.75–3.95), musculoskeletal (aOR = 1.90; 95% CI = 1.43–2.52), and skin (aOR = 1.54; 95% CI = 1.06–2.22) SDI domains. Dissecting domains into items, NPSLE was associated with coronary artery disease (aOR = 3.08; 95% CI = 1.44–6.58), myocardial infraction (aOR = 3.11; 95% CI = 1.54–6.27), muscle atrophy (aOR = 3.34; 2.16–5.16), scarring alopecia (aOR = 1.79; 95% CI = 1.19–2.70), bowel infarction (aOR = 1.98; 95% CI = 1.20–3.26), retinopathy (aOR = 2.23; 95% CI = 1.15–4.32), and premature gonadal failure (aOR = 2.10; 95% CI = 1.11–3.90). Conclusion The intricate association between NPSLE and damage accrual extends beyond the nervous system to also comprise the musculoskeletal, skin, and cardiovascular organ systems.