Predictors of renal flares in systemic lupus erythematosus: a post-hoc analysis of four phase III clinical trials of belimumab
2024 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, article id keae023Article in journal (Refereed) Epub ahead of print
Abstract [en]
OBJECTIVES: To identify predictors of renal flares in patients with SLE treated for active extra-renal disease.
METHODS: Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through 52-76 weeks using proportional hazards regression analysis.
RESULTS: Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement (HR: 15.4; 95% CI: 8.3-28.2; p< 0.001), low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; p< 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; p< 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; p< 0.001) at baseline appeared robust determinants of renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; p< 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; p< 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; p= 0.001).
CONCLUSION: A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. Beyond anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.
Place, publisher, year, edition, pages
Oxford University Press, 2024. article id keae023
Keywords [en]
Belimumab, biologics, biomarkers, renal flares, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:oru:diva-110707DOI: 10.1093/rheumatology/keae023ISI: 001155690700001PubMedID: 38216728OAI: oai:DiVA.org:oru-110707DiVA, id: diva2:1827609
Funder
AstraZenecaEli Lilly and CompanySwedish Rheumatism Association, R-98222King Gustaf V Jubilee Fund, FAI-2020–0741]Swedish Society of Medicine, SLS-974449Nyckelfonden, OLL-974804Region Stockholm, FoUI-955483Karolinska Institute
Note
This work was supported by grants from the Swedish Rheumatism Association [R-982223]; the King Gustaf V’s 80-year Foundation [FAI-2020–0741]; the Swedish Society of Medicine [SLS-974449]; Nyckelfonden [OLL-974804]; the Professor Nanna Svartz Foundation [2020–00368]; the Ulla and Roland Gustafsson Foundation [2023–35]; the Region Stockholm [FoUI-955483]; and the Karolinska Institutet.
Disclosure statement: I.P. has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Bristol-Myers Squibb, Elli Lilly, Gilead, GlaxoSmithKline, Janssen ,Novartis, Otsuka, and Roche.
2024-01-152024-01-152024-02-14Bibliographically approved