Efficacy and safety of belimumab in refractory and newly diagnosed active lupus nephritis patients: a real-world observational study

Background Lupus nephritis (LN), one of the common manifestations of systemic lupus erythematosus, continues to be a principal cause of morbidity and mortality. According to the 2024 Kidney Disease: Improving Global Outcomes guidelines, belimumab has been recommended as adjunct therapy for active LN. However, the differences in its efficacy and safety between refractory and newly diagnosed active LN are unknown. This study aimed to evaluate them in a real-world clinical setting in China. Methods We enrolled active LN patients who initiated belimumab as adjunct therapy in our centre between June 2021 and January 2024 and divided them into a refractory group and a newly diagnosed group according to previous immunosuppressive therapy. They were followed up for >= 3 months. Renal manifestations, serologic features, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score and steroids dosage were recorded. We used generalized estimating equations to compare time series data for each group and analyse the change tendency of variables over time. Efficacy endpoints were complete renal response (CRR) and primary efficacy renal response (PERR). Logistic regression models were used to analyse factors associated with renal response. Results Of 116 LN patients receiving belimumab in our centre, a total of 89 active LN patients were included in the analysis, with a median treatment duration of 13 months (range 7-22). Among them 47 were in the newly diagnosed group and 42 were in refractory group. At the initiation of belimumab there is no statistical difference in age, gender, SLEDAI-2K score, renal-related markers (proteinuria, serum albumin, estimated glomerular filtration rate and renal histological classification) and serologic features (positive anti-double-stranded DNA, C3, C4) between the two groups. Compared with refractory patients, newly diagnosed patients had significantly shorter LN duration (P < .001) and a larger dosage of steroids (P < .01). During the follow-up period, proteinuria, SLEDAI-2K score and dosage of steroids decreased overall and in each group. The decrease was significantly more pronounced in the newly diagnosed group (P < 0.01, P < 0.001, P < 0.001). For the refractory active LN patients, the estimated probability of CRR and PERR at 12 months was 58.3% and 65.4%, respectively, which was comparable to newly diagnosed patients by logrank test (P = .10, P = .51). No difference was found in adverse event rates (P = .08), time to first renal flare (P = .79) or renal-related events (P = .77). Proteinuria levels at belimumab initiation [odds ratio (OR) 1.306, P = .02] and belimumab treatment duration (OR 0.896, P = .01) were independently associated with renal response. Conclusion Compared with refractory LN patients, the add-on treatment with belimumab provides remarkable improvement in newly diagnosed active LN patients, with faster steroids decrease. Our data support the efficacy of early introduction of belimumab in Chinese active LN patients in a real-life setting.