Effect of Belimumab on Preventing de novo Renal Lupus Flares

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.