Determinants of neuropsychiatric flares in patients with systemic lupus erythematosus: results from five phase III trials of belimumabShow others and affiliations
2024 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 63, no 3, p. 798-808Article in journal (Refereed) Published
Abstract [en]
OBJECTIVE: To identify determinants of neuropsychiatric (NP) flares in patients with systemic lupus erythematosus (SLE) treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo.
METHODS: We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; N = 3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression. In a subgroup analysis, we studied patients with baseline NP BILAG E for determinants of de novo NPSLE flare. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). RESULTS: We documented 105 (2.9%) NPSLE flares. 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 increasing SDI scores (HR = 1.35; 95% CI: 1.21-1.50; p < 0.001) were strongly associated with NPSLE flare. Belimumab use yielded no association at any dose or administration form. In analysis of SDI domains, NP damage was the strongest determinant of NPSLE flare (HR = 3.25; 95% CI: 2.72-3.88; p < 0.001), holding true for 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). Male sex was the strongest determinant of de novo NPSLE flare (HR = 3.26; 95% CI: 1.51-7.04; p = 0.003).
CONCLUSION: Male sex, NPSLE history, and NP damage were strong determinants of impending NPSLE flare. No clear protection or predisposition was conferred from add-on belimumab.
Place, publisher, year, edition, pages
Oxford University Press, 2024. Vol. 63, no 3, p. 798-808
Keywords [en]
Belimumab, determinants, flares, neuropsychiatric, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:oru:diva-106049DOI: 10.1093/rheumatology/kead249ISI: 001010366000001PubMedID: 37228034Scopus ID: 2-s2.0-85178279237OAI: oai:DiVA.org:oru-106049DiVA, id: diva2:1759483
Funder
Swedish Rheumatism Association, R-969696King Gustaf V Jubilee Fund, FAI-20200741Swedish Society of Medicine, SLS-974449Nyckelfonden, OLL-974804Region Stockholm, FoUI-955483Karolinska Institute
Note
Funding agencies:
Professor Nanna Svartz Foundation 202100436
Ulla and Roland Gustafsson Foundation 202126
2023-05-262023-05-262024-03-22Bibliographically approved