Predictors and prevention of renal flares: Pooled analysis of four phase III trials of belimumab

Renal involvement occurs in 30–60% of the patients with systemic lupus erythematosus (SLE) and remains a substantial contributor to end-stage kidney disease, dialysis, and mortality.^1,2 However, there is uncertainty in the identification of circumstances leading to renal flares and belimumab’s efficacy in preventing them.^1,2

Below, we summarize a pooled analysis of four phase III trials of belimumab assessing predictors of renal flares in patients with SLE, published by Jägerback et al.¹ in Rheumatology; and on their prevention using belimumab alongside antimalarials, published by Gomez et al.² in Rheumatology.

Methods^1,2

• A post-hoc analyses of four phase III trials of belimumab in patients with active extrarenal SLE:

• • BLISS-52, NCT00424476
  • BLISS-76, NCT00410384
  • BLISS-Northeast Asia, NCT01345253
  • BLISS-SC, NCT01484496

• Patients were administered different doses of belimumab (intravenous [IV] 1 mg/kg, IV 10 mg/kg, and subcutaneous 200 mg) or placebo on top of standard therapy.
• Patients received follow-ups from Weeks 52–76. Predictors of renal flares were assessed using proportional hazards regression analysis,¹ and the effect of antimalarials and different doses of belimumab on renal flares was assessed using Cox regression analysis.²

Key findings^1,2

• Of 3,225 patients with SLE, 192 developed ≥1 renal flare, with the first occurring after a median follow-up of 197 days.
  • The patients had a mean age of 36.7 years, with 94% being women, and 54.6% had current/former renal involvement at baseline.
• The most robust determinants of impending renal flares were current/former renal involvement (hazards ratio [HR]: 15.4; 95% confidence interval [CI], 8.3–28.2; p < 0.001], low serum albumin levels, proteinuria, and low C3 levels at baseline (Figure 1)
  • Anti-dsDNA and anti-Smith positivity were also associated with renal flares (Figure 1); however, the association reduced after adjustments

Figure 1. Predictors of renal flares*

BAFF, B-cell activating factor; CI, confidence interval; dsDNA, double-stranded DNA; HR, hazard ratio.
*Adapted from Jägerback, et al.¹

• Treatment with belimumab IV 10 mg/kg and 1 mg/kg resulted in a significantly reduced risk of renal flares (HR, 0.62; 95% CI, 0.41–0.92; p = 0.018 and HR, 0.42; 95% CI, 0.22–0.79; p = 0.007, respectively), while no significant association was found for subcutaneous 200 mg, compared with placebo.
• While antimalarials led to a lower hazard of renal flares (HR, 0.66; 95% CI, 0.55–0.78; p < 0.001), the prevention was conferred when antimalarials were coadministered with belimumab, particularly with the IV 1 mg/kg dose (Figure 2).

Figure 2. Incidence rate of renal flares comparing different belimumab doses with and without antimalarials* 

AMA, antimalarial; IV, intravenous; SC, subcutaneous.
*Data from Gomez, et al.²