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. 2024 Sep;44(9):1679-1689.
doi: 10.1007/s00296-024-05667-5. Epub 2024 Aug 8.

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

Dionysis Nikolopoulos  1   2 , Nursen Cetrez  3   4 , Julius Lindblom  3   4 , Ioannis Parodis  3   4   5
Affiliations

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

Dionysis Nikolopoulos et al. Rheumatol Int. 2024 Sep.

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.

Trial registration: ClinicalTrials.gov NCT00424476 NCT00410384 NCT01484496 NCT01345253 NCT01632241.

Keywords: Nervous system; Neuropsychiatric lupus; Outcomes; SLICC/ACR damage index; Systemic lupus erythematosus.

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Conflict of interest statement

IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Bristol-Myers Squibb, Elli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Otsuka, and Roche. The other authors declare that they have no conflicts of interest related to this work. The funders had no role in the design of the study, the analyses or interpretation of data, or the writing of the manuscript.

Figures

Fig. 1
Fig. 1
Associations between NPSLE and neuropsychiatric, cardiovascular, and vascular damage. (A) Bar plots illustrating the mean (± SD) SDI score in the neuropsychiatric, cardiovascular, and vascular SDI domains between NPSLE (green) and non-neuropsychiatric SLE (blue) patients. The Mann–Whitney U test was applied to compare the two groups. (B) Forest plot showing the odds ratios (ORs) and 95% confidence intervals (CIs) deriving from logistic regression analysis adjusting for age, sex, disease duration, and ethnicity. A higher OR indicates greater risk of established organ damage. CI confidence interval; NPSLE neuropsychiatric systemic lupus erythematosus; OR odds ratio; SD standard deviation; SDI Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index; SLE Systemic Lupus Erythematosus
Fig. 2
Fig. 2
Associations between NPSLE and skin, musculoskeletal, and renal damage. (A) Bar plots illustrating the mean (± SD) SDI score in the skin, musculoskeletal, and renal SDI domains between NPSLE (green) and non-neuropsychiatric SLE (blue) patients. The Mann–Whitney U test was applied to compare the two groups. (B) Forest plot showing the odds ratios (ORs) and 95% confidence intervals (CIs) deriving from logistic regression analysis adjusting for age, sex, disease duration, and ethnicity. A higher OR indicates greater risk of established organ damage. CI confidence interval; NPSLE neuropsychiatric systemic lupus erythematosus; OR odds ratio; SD standard deviation; SDI Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index; SLE Systemic Lupus Erythematosus
Fig. 3
Fig. 3
Associations between NPSLE and ocular, pulmonary, gastrointestinal damage, premature gonadal failure, diabetes, and malignancies. (A) Bar plots illustrating the mean (± SD) SDI score in the ocular, pulmonary, and gastrointestinal SDI domains between NPSLE (green) and non-neuropsychiatric SLE (blue) patients. The Mann–Whitney U test was applied to compare the two groups. (B, C) Forest plot showing the odds ratios (ORs) and 95% confidence intervals (CIs) deriving from logistic regression analysis adjusting for age, sex, disease duration, and ethnicity. A higher OR indicates greater risk of established organ damage. CI confidence interval; NPSLE neuropsychiatric systemic lupus erythematosus; OR odds ratio; SD standard deviation; SDI Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index; SLE Systemic Lupus Erythematosus
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