TRIPLE THERAPY WITH BELIMUMAB IN PROLIFERATIVE LUPUS NEPHRITIS: REAL-WORLD EFFICACY AND GLUCOCORTICOID-SPARING EFFECTS

PT016 / #756 Topic: AS15 - Lupus Nephritis-Clinical POSTER TOUR 03: RECENT ADVANCEMENTS IN SLE CLINICAL OUTCOMES AND THERAPY 23-05-2025 10:00 AM - 10:40 AM Background/Purpose The newly published ACR guidelines recommend initiating triple therapy for all patients with proliferative lupus nephritis (LN). In alignment with EULAR and KDIGO recommendations, treatment goals include achieving the 2019 EULAR/ERA-EDTA targets: a reduction in proteinuria by ≥25% at 3 months, ≥50% at 6 months, and <500–700 mg/day at 12 months, while maintaining an estimated glomerular filtration rate (eGFR) within 10% of baseline. The ultimate objective is to achieve complete renal response (CRR) within 12 months of initiating therapy. Additionally, these guidelines emphasize the importance of achieving these targets with the lowest possible glucocorticoid (GC) dose, aiming for a progressive reduction to a maintenance dose of ≤5 mg/day of prednisone, and ultimately discontinuing GC. The aim of this study is to assess the efficacy of triple therapy with belimumab (BEL) added to standard of care (SoC) within the first 6 months of LN onset in achieving renal response, meeting EULAR/ERA-EDTA targets, and evaluating its GC-sparing effect in a real-world clinical setting. Methods This retrospective, multicenter study was conducted across 4 hospitals in Barcelona. Patients with biopsy-proven proliferative LN (ISN/RPS class III, IV, or mixed III/IV+V) who received triple therapy including BEL within the first 6 months after LN onset were included. The primary endpoint was the achievement of CRR at 1 year. Results A total of 17 patients (82.4% women, mean age at renal biopsy 39.7 ± 14 years) were analyzed. The majority were Caucasian (58.9%), followed by Hispanic (29.4%) and Asian (11.8%). A history of previous LN episodes was present in 35.3% of patients, with 2 patients experiencing 2 prior flares. All patients had proliferative LN: 23.5% class III, 35.2% class IV, and 41.2% mixed (III/IV + V). The mean activity index was 8.1 ± 3.3 and the chronicity index 2.33 ± 2.3; 1 patient had thrombotic microangiopathy. Induction therapy included 3 methylprednisolone pulses in 52.9%, with a mean initial oral prednisone dose of 37.9 ± 14.9 mg/day. Most patients (76.5%) received MMF, while 23.5% were treated with CYC. For maintenance, 94.1% remained on MMF, with 1 patient receiving azathioprine. At renal flare, mean proteinuria was 3.3 ± 3.2 g/day, eGFR 68 ± 23.1 mL/min/1.73m², and serum creatinine 144 ± 156 μmol/L. Their evolution is summarized in Table 1. Table 1. By 12 months or earlier, 64.7% (11/17) of patients achieved CRR, with a median time to response of 6 months (IQR 4–12) (Figure 1). Among the 6 remaining patients, 1 achieved CRR at 26 months, 3 experienced renal relapse (13.6%) while on treatment, 1 progressed to end-stage renal disease (this patient had a chronicity index of 8 and a history of 2 prior LN episodes), and 1 discontinued BEL at 8 months due to an extrarenal flare. BEL demonstrated a significant GC-sparing effect: at 3 months, 64.7% required <10 mg/day of prednisone; by 6 months, 64.7% needed <5 mg/day, and at 12 months, 84.2% achieved doses <5 mg/day (Figure 2). Figure 1. Figure 2. When comparing early (<3 months) versus late (3–6 months) initiation of BEL, early initiation was associated with a significantly higher likelihood of achieving CRR, with a hazard ratio of 4.34 (95% CI: 1.06–17.76; p = 0.041). Additionally, the median time to CRR was significantly shorter in the early initiation group (6 months vs 13 months). Conclusions In our experience, triple therapy with BEL achieved EULAR/ERA-EDTA targets while significantly reducing glucocorticoid requirements, particularly with early initiation.

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