Effect of Belimumab on Preventing de novo Renal Lupus Flares

Ioannis Parodis; Julius Lindblom; Nursen Cetrez; Leonardo Palazzo; Henri Ala; Frédéric A Houssiau; Christopher Sjöwall; Brad H Rovin

doi:10.1016/j.ekir.2023.06.021

Effect of Belimumab on Preventing de novo Renal Lupus Flares

Kidney Int Rep. 2023 Jul 6;8(9):1822-1830. doi: 10.1016/j.ekir.2023.06.021. eCollection 2023 Sep.

Authors

Ioannis Parodis^{1

2}, Julius Lindblom¹, Nursen Cetrez¹, Leonardo Palazzo¹, Henri Ala¹, Frédéric A Houssiau³, Christopher Sjöwall⁴, Brad H Rovin⁵

Affiliations

¹ Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
² Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
³ Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
⁴ Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden.
⁵ Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA.

Abstract

Introduction: Belimumab was recently approved for treating lupus nephritis (LN), yet de novo LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative.

Methods: We evaluated belimumab efficacy in preventing de novo renal flares and factors associated with renal flare occurrence in nephritis-naïve patients with systemic lupus erythematosus (SLE) who are receiving add-on belimumab or placebo in 5 phase 3 clinical trials using Cox regression analysis.

Results: Of 1844 eligible patients, 136 (7.4%) developed a de novo renal flare during a 52-week long follow-up. Asian origin (Adjusted Hazard Ratio [HR_adj]: 1.97; 95% confidence interval [CI]: 1.32-2.94; P = 0.001), positive baseline anti-double stranded DNA (anti-dsDNA) levels (HR_adj: 1.32; 95% CI: 1.07-1.63; P = 0.008), and increasing mean prednisone dose during follow-up (HR_adj: 1.03; 95% CI: 1.02-1.04; P < 0.001) were associated with de novo renal flares. Low-dose intravenous (IV) belimumab (1 mg/kg monthly) yielded a nearly 3-fold lower hazard of de novo renal flare (HR_adj: 0.38; 95% CI: 0.20-0.73; P = 0.004). Subcutaneous (SC) belimumab (200 mg weekly) also yielded a lower hazard (HR_adj.: 0.69; 95% CI: 0.54-0.88; P = 0.003). The labeled IV dose (10 mg/kg monthly) conferred no clear protection (HR_adj.: 0.74; 95% CI: 0.50-1.09; P = 0.127).

Conclusion: We corroborated the substantial vulnerability of the Asian SLE population to renal affliction. Add-on low-dose IV belimumab (1 mg/kg) and SC belimumab appeared protective against renal flares in nephritis-naïve patients with SLE. The approved IV dose (10 mg/kg) yielded no clear protection.

Keywords: belimumab; flares; kidney disease; lupus nephritis; predictors; systemic lupus erythematosus.