Background Belimumab has shown ability to reduce flare rates in systemic lupus erythematosus (SLE), but little is known about its potential benefits in neuropsychiatric (NP)SLE. We investigated predictors of NP flares in SLE patients under standard therapy with or without add-on belimumab.
Methods Data from five clinical trials of belimumab in SLE (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE) were utilised (N=3638). Flares were defined using the British Isles Lupus Assessment Group (BILAG) activity index. Predictors of flares were investigated throughout a 52-week follow-up using univariable and multivariable Cox regression. A subgroup analysis in patients with baseline NP BILAG E was performed to determine predictors of de novo NP flare. Organ damage was assessed using the SLICC/ACR Damage Index (SDI).
Results In total, 105 (2.9%) NP flares were documented. In multivariable analysis, male sex (HR: 2.37; 95% CI: 1.31–4.28; p=0.004), baseline NP BILAG B-D (HR: 5.91; 95% CI: 3.86–9.06; p<0.001), and high baseline SDI score (HR: 1.35; 95% CI: 1.21–1.50; p<0.001) were highly associated with NP flare development. Belimumab use yielded no clear protection. In a separate analysis of SDI domains, the NP domain (HR: 3.25; 95% CI: 2.72–3.88; p<0.001) was the strongest predictor of NP flare, with cognitive impairment (HR: 14.29; 95% CI: 9.22–22.14; p<0.001), transverse myelitis (HR: 21.89; 95% CI: 5.40–88.72; p<0.001), and neuropathy (HR: 8.87; 95% CI: 5.59–14.09; p<0.001) mainly driving this association. In the subgroup analysis of the NP BILAG E population, male sex was the strongest predictor of de novo NP flare (HR: 3.26; 95% CI: 1.51–7.04; p=0.003).
Conclusions Current or former NPSLE activity and established organ damage in the NP domain at baseline were the strongest predictors of NP flare. Whether belimumab treatment protects against NP events remains unclear.
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