Guide
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple tissues, and lupus nephritis (LN) is one of the most severe and common manifestations of SLE. Without effective treatment, LN may lead to irreversible structural or functional damage that affects the prognosis of patients with SLE, so early recognition and intervention of LN is crucial. Treatment of LN usually requires long-term use of glucocorticoids and immunosuppressants to control disease activity and preserve renal function, but the current clinical response rate is not ideal.
In clinical practice, belimumab has been shown to be an effective biologic agent for improving LN, but in China, belimumab for the treatment of LN patients is still in the early stages, and further studies are needed to confirm safety and efficacy. This retrospective comparative study aims to evaluate the clinical efficacy and safety of belimumab in the treatment of LN in the real world, providing key insights into the use of belimumab in Chinese patients with LN.
Study design
Studies were divided into usual care and belimumab (10 mg/kg of belimumab on days 1, 15, and 29, and the same dose every 28 days). Regular follow-up visits were followed up, and data from months 3, 6 and 12 were collected for analysis.
Diagnosis of SLE is based on the SLICC/United States College of Rheumatology (ACR) classification criteria or the 1997 ACR revision criteria, and LN is based on a persistently positive renal biopsy or urine test.
Complete renal response (CRR) is defined as proteinuria less than 0.5 g/24 hours or 50 mg/mmol, improved or stable renal function (at least normal or ≥ 10% of baseline); Partial renal response (PRR) is defined as proteinuria less than 3.0 g/24h and greater than 50% reduction from baseline, with improved or stable renal function. Remission is defined as clinical SLE disease activity score (SLEDAI)-2K score = 0 (except serology), PGA score <0.5 and receiving an equivalent glucocorticoid dose of ≤5 mg/day, with stable antimalarials, immunosuppressants, and biologics. Lupus low disease activity status (LLDAS) is defined as SLEDAI-2K≤4, no active disease in central organ systems, PGA score ≤ 1.0, no new active disease, glucocorticoid dose ≤7.5 mg/d, standard dose of antimalarials, immunosuppressants, and biologics. Disease severity subgroups were classified as mild (0-6), moderate (7-12), and severe (>12) based on SLEDAI scores.
Findings:
A total of 96 patients with LN were included in the study, including 54 in the belimumab group and 42 in the conventional treatment group, and the baseline characteristics of the patients are shown in Table 1.
Table 1: Baseline characteristics of patients
(Click to expand)
- Renal manifestations
At 3 months of belimumab treatment, the proportion of patients with proteinuria decreased from 74.1% to 64.8% (P<0.001), the proportion of patients with hematuria decreased from 59.3% to 37.0% (P=0.008), and the proportion of patients achieving PRR or CRR increased from 53.7% to 75.9% (P<0.001) (Figure 1).
Figure 1: Renal remission during belimumab treatment
- Serologic assessment, glucocorticoid dose, and disease activity assessment
Serologic evaluation showed that at 6 months (0.66 g/L vs 0.76 g/L, p=0.02) and 12 months (0.60 g/L versus 0.75 g/L, p=0.015), C3 levels were significantly lower in the belimumab group than in the usual care group (Figure 2A).
Dose evaluation of glucocorticoids showed that the median dose of glucocorticoids decreased from 30 mg/day to 17.5 mg/day (P<0.001) within 3 months of belimumab treatment (Fig. 2B), and the proportion of patients requiring glucocorticoids of >5 mg/day decreased from 88.89% to 79.07% (P<0.001) after 6 months of belimumab treatment.
Disease activity assessment showed that the median SLEDAI score decreased from 10 to 5 (p<0.001) in the belimumab group after 3 months of treatment compared with baseline (Fig. 2C), and the proportion of patients achieving LLDAS increased from 11.11% to 16.67% (p<0.001). At 6 months, the SLEDAI score in the belimumab group was significantly lower than that in the usual care group (p=0.014) (Fig. 2C), and the proportion of patients achieving remission was significantly higher than that in the usual care group (p=0.026) (Fig. 2D).
Figure 2: Comparison of efficacy between conventional treatment and belimumab
（A）补体3水平（g/L）。 （B）口服糖皮质激素剂量（mg/d）。 （C）SLEDAI评分。 （D）缓解率（%）。 *p<0.05；**p<0.01
- Treatment-period adverse events (TEAEs)
The incidence of TEAEs was significantly lower in the belimumab group than in the usual care group (29.6 versus 52.4 percent, p=0.024), and the incidence of respiratory tract infections was significantly lower (7.4 versus 23.8 percent, p=0.049). TEAEs were predominantly mild to moderate, improved with symptomatic treatment, and there were no deaths during the study period.
Research Discussion
This study suggests that belimumab has advantages in renal remission, glucocorticoid dose reduction, and safety. Consistent with previous studies, the combination of belimumab and glucocorticoids and immunosuppressants resulted in an overall improvement in clinical response and disease activity in patients with LN, with approximately 95% of patients receiving the belimumab combination achieving partial or complete renal remission at the last visit. In addition, this study covers a broader population of LN patients, including patients with chronic kidney disease stage 4 and 5, patients receiving hemodialysis or peritoneal dialysis, and patients previously treated with rituximab. At the same time, this study also showed that patients were better tolerated with belimumab, and the incidence of TEAEs was lower in the belimumab group, which may be related to the faster tapering of glucocorticoids and immunosuppressants.
conclusion
This review provides strong evidence to support the benefits of belimumab in improving renal function, reducing disease activity, reducing glucocorticoid doses, and TEAEs in Chinese patients with LN, but further controlled, large-scale, randomized clinical trials are needed to confirm and validate these findings.
引用文献：Lin Z, Jiang B, Wang W, et al. Clinical outcomes in lupus nephritis patients treated with belimumab in real-life setting: a retrospective comparative study in China. PeerJ. 2024; 12:e18028. Published 2024 Sep 19. doi:10.7717/peerj.18028
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