Efficacy and safety of belimumab combined with the standard regimen in treating children with lupus nephritis

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Methods: This was a single-center, retrospective cohort study. We collected the clinical data of children with newly active LN hospitalized in the Department of Nephrology between December 2004 and February 2023. The children were divided into belimumab and traditional treatment groups according to whether they received belimumab or not. The renal remission rate, recurrence rate, and glucocorticoid dose were compared between both groups. Results: 1) Baseline data of clinical and pathology: 47 children with a median age of 11 years were enrolled in this study, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ±7.78) was higher than that for those in the traditional treatment group (19.13 ±6.10) ( t =2.176, P =0.035). The two groups showed no significant difference in pyuria, gross hematuria, 24-h urinary protein, and estimated glomerular filtration rate. In all cases, acute glomerulonephritis (34.0%) and nephrotic syndrome (48.9%) were the most common, and there were no differences in the clinical classification between both groups (χ2=2.192, P =0.533). Forty-two children completed renal biopsy, and there were no differences in the distribution of pathological classification and the activity and chronic indices between both groups ( χ 2 = 4.441, P =0.35; t = 0.935, P = 0.357; Z =1.244, P = 0.322). 2) Efficacy: The complement C3/C4 in the belimumab group was faster than that in the traditional treatment group 3, 6, and 12 months after treatment ( P <0.05). The average SLEDAI-2000 score showed no difference in both groups at 6 and 12 months ( P =0.799; P =0.132). There were no differences in the complete remission rate between both groups at 6 months and 12 months (χ2=1.631, P =0.442; χ2=0.094, P =0.759). The 1-year recurrence rate was 13.3% in the traditional treatment group, and there was no clinical recurrence in the belimumab group (χ2=1.061, P =0.303). Furthermore, 6 months after treatment, the glucocorticoid dose in the belimumab group (17.87 ±6.96 mg/d) was significantly lower than that in the traditional treatment group (27.33 ±8.40 mg/d) ( P =0.000). At 12 months of treatment, the glucocorticoid dose in the belimumab group [10.00 (5.3) mg/d] was also significantly lower than that in the traditional treatment group [13.75 (10.0) mg/d] ( p =0.007). 3) Safety: there was no infusion reaction during belimumab treatment. Nine cases (52.9%) had two to four episodes of acute upper respiratory tract infections, one (5.9%) had gastroenteritis, one (5.9%) had tinea versicolor, and one (5.9%) had a varicella-zoster virus infection. The infection was relieved within 1 week without serious adverse reactions. During belimumab therapy, the levels of serum immunoglobulin M (IgM), IgG, and IgA showed a decreasing trend at 6 and 12 months compared with baseline, but there was no statistically significant difference ( P >0.5). Conclusion: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen can reduce the dosage of glucocorticoids. The incidence of adverse events is low and generally in control. Lupus nephritis children Belimumab Efficacy Safety Figures Figure 1 Figure 2 Figure 3 What is Known •Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy • Due to the paucity of studies, its efects and side efects in children with LN remain unclear. What is New: • This was a single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • With an equivalent renal remission rate, belimumab combined with the standard traditional regimen can reduce the dosage of glucocorticoids. The incidence of adverse events is low and generally in control. Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease that invades multiple organs and systems. Childhood-onset SLE accounts for only 15–20% of all SLE cases [ 1 ]; however, it is more acute, affects more systems, has a more active course, and has a worse prognosis than adult SLE, especially in patients with kidney involvement. Consequently, over 50% of children with SLE develop lupus nephritis (LN) [ 2 ], usually within the first 2 years of diagnosis [ 3 ]. The standard induction regimen of corticosteroids combined with immunosuppressants, including cyclophosphamide (CTX) or mycophenolate mofetil (MMF), has improved the renal prognosis; however, over one-third of children may still experience recurrence after remission [ 2 ] Belimumab can bind to B cell-activating factor (BAFF) (also known as B lymphocyte stimulator, Blys) with high affinity. It blocks Blys from binding to receptors on B cells and inhibits B cell proliferation and plasma cell differentiation, thereby reducing the production of autoantibodies in the serum and thus treating SLE [ 4 ]. As the first biologic approved for SLE treatment in children aged ≥ 5, it was also approved on February 10, 2022, to be combined with conventional therapy for active LN in adults. However, research on the clinical application of belimumab in children with LN is limited. Therefore, we collected clinical data from patients with active LN who received belimumab combined with standard traditional regimens at our center. We aimed to evaluate the efficacy and safety of belimumab in this population and provide a reference for its clinical application in pediatrics. Materials and Method Research participants This single-center, retrospective cohort study collected the clinical data of newly diagnosed patients with active LN hospitalized in the nephrology department between December 2004 and February 2023. Grouping The participants were divided into belimumab and traditional treatment groups based on whether or not they received belimumab treatment. (1) Traditional treatment: All patients were administered glucocorticoids or immunosuppressants. The immunosuppressants included CTX, MMF, cyclosporine A, and tacrolimus. The specific treatment plans are provided in the guidelines [ 6 ] and were determined based on the patient's condition. (2) The treatment regimen of belimumab was an intravenous infusion of 10 mg/kg at weeks 0, 2, and 4, followed by another intravenous infusion of 10 mg/kg every 4 weeks for a maximum duration of 52 weeks. Observation and evaluation indicators (1) Data on sex, age, LN course, clinical and pathological classification, and extrarenal-affected organs in the two groups of children at the time of enrollment and follow-up were collected through outpatient follow-up visits and readmission medical records or phone calls after discharge. (2) Observation indicators: Laboratory indicators of patients at 0, 6, and 12 months after treatment included 24-h urine protein output and estimated glomerular filtration rate (eGFR) based on the Schwartz formula. (3) Effectiveness evaluation: Indicators such as renal remission rate, recurrence rate, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score, and glucocorticoid dosage at 6 and 12 months of treatment were evaluated. (4) Safety evaluation: During the follow-up period of belimumab treatment, adverse events, including infusion reactions, hypersensitivity reactions, infections, and blood immunoglobulin levels, were recorded. Treatment response [ 7 ] (1) Complete remission (CR): Normal renal function (eGFR > 90 mL/min/1.73 m 2 ), proteinuria < 0.5 g/d or urine protein: creatinine ratio (UPCR) 50% from baseline. (3) No renal remission (NR): failure to achieve partial or complete remission within 6–12 months of therapy. (4) Recurrence: In patients with complete remission, proteinuria increased by > 50%, and/or GFR decreased by > 25% from baseline. Statistical methods SPSS 26 software was used for statistical analysis, and the count data were presented as the number of cases (percentage). Intergroup comparison was applied: χ2 tests or Fisher's exact probability method. If the measurement data conforms to a normal distribution, it is expressed as mean ± standard deviation, and a t-test is used for intergroup comparison. However, the Mann–Whitney U rank sum test is used for intergroup comparison of non-normally distributed econometric data represented as M (1/4, 3/4). Statistical significance was set at P < 0.05. Results 1. General information: Forty-seven cases were enrolled, with a median age of 11.0 years (9.0, 12.0 years), including 18 males (38.3%) and 29 females (61.7%). In the traditional treatment group, there were 30 cases with a median age of 10.5 years (8.75, 12.0 years), including 13 males (43.3%) and 17 females (56.7%). The initial diagnosis was between December 2004 and April 2022. The belimumab group had 17 cases, with a median age of 11.0 years (9.0, 13.0 years), including five males (29.4%) and 12 females (70.6%). The initial diagnoses were made between September 2020 and February 2023. 2. Clinical manifestations and treatment: 1) Extrarenal manifestations: At disease onset, there were no statistically significant differences between the two groups regarding the extrarenal organs involved, including the skin, mucosa, musculoskeleton, blood, nervous system, and complement C3/C4 levels. The SLEDAI-2000 score in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10), with statistical significance (t = 2.176, P = 0.035). 2) Renal changes: The two groups had no significant differences in pyuria, gross hematuria, 24-h urine protein content, or eGFR. Among all cases, acute nephritis (16/47, 34.0%) and nephrotic syndrome (23/47, 48.9%) were the most common, and there was no statistically significant difference in clinical subtype distribution between both groups (χ2 = 2.192, P = 0.533). Forty-two pediatric patients underwent renal tissue biopsy, of which 41 (97.6%) were type III (including type III + V) and type IV (including type IV + V), with type IV being the most common. There was no statistically significant difference in pathological subtype distribution between both groups (χ2 = 4.441, P = 0.35). The belimumab group’s average activity index (10.47 ± 2.72) was higher than that of the traditional treatment group (9.59 ± 2.78). However, there was no statistically significant difference (t = 0.935, P = 0.357), and the median chronic index between both groups was not statistically different (Z = 1.244, P = 0.322) (Table 1 ). Table 1 Comparison of baseline clinical and laboratory data between the traditional treatment group and the belimumab group Traditional treatment group (n = 30) Belimumab group (n = 17) t/Z/χ 2 值 P Male (n %) 13 (43.3) 5 (29.4) 0.89 0.345 Age (year) 10.10 ± 3.11 11.00 ± 2.78 –0.989 0.328 Organ involvement Mucocutaneous 14 (46.7) 9 (52.9) 0.171 0.679 musculoskeletal 6 (20.0) 4 (23.5) 0.008 0.931 Hematologic 24 (80.0) 17 (100.0) 2.309 0.129 Nervous system 6 (20.0) 3 (17.7) 0.036 0.85 Kidney Gross hematuria 14 (46.7) 7 (41.2) 0.132 0.716 Pyuria 21 (70.0) 13 (76.5) 0.061 0.805 UTP (mg/kg.d) 63.3 (22.3,146.2) 75.9(34.5,117.0) –0.133 0.894 Scr (umol/L) 62.54 (48.5,74.6) 65.50(49.5,102.4) –0.831 0.406 eGFR (mL/min.1.73 m 2 ) 94.72 ± 32.07 81.02 ± 37.88 1.298 0.201 Clinical typing (n %) 2.192 0.533 Hematuria proteinuria type 3 (10.0) 2 (11.8) Nephrotic syndrome type 12 (40.0) 4 (23.5) Acute nephritis type 14 (46.7) 9 (52.9) Acute progressive nephritis type 1 (3.33) 2 (11.8) Pathological classification (n %) 4.441 0.35 Ⅱ 1 (4.0) 0 (0.0) Ⅲ 1 (4.0) 0 (0.0) Ⅳ 19 (76.0) 15 (88.2) Ⅲ+Ⅴ 1 (4.0) 2 (11.8) Ⅳ+Ⅴ 3 (12.0) 0 (0.0) AI 9.59 ± 2.78 10.47 ± 2.72 –0.935 0.357 CI 0.0 (0.0.1.5) 0.0 (0.0.0.0) –1.244 0.322 C3 (g/L) 0.27 (0.2,0.5) 0.32 (0.2,0.4) –0.444 0.657 C4 (g/L) 0.04 (0.0,0.1) 0.06 (0.0,0.1) –0.692 0.489 SLEDAI-2000 19.13 ± 6.10 23.59 ± 7.78 –2.176 0.035 UTP, Uridine-5′-triphosphate; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; SLEDAI-2000, Systemic Lupus Erythematosus Disease Activity Index-2000 Immune induction therapy: Among the two groups, CTX was the most commonly used immunosuppressive induction therapy, with 39 cases. Among them, the traditional treatment and belimumab groups had 27 (93.10%) and 12 cases (70.59%), respectively; joint calcineurin inhibitor class (χ2 = 1.951, P = 0.163) and hydroxychloroquine (χ2 = 0.171, P = 0.679) but there was no difference in treatment between the two groups. Four children were treated with blood purification, including two continuous bedside blood filtration, one peritoneal dialysis, and one plasma exchange (Table 2 ). Table 2 Comparison of induction therapy between the traditional treatment and belimumab groups Traditional treatment group (n = 30) Belimumab group (n = 17) χ 2 P Immune induction therapy n (%) 2.647 0.104 GC + CTX 27 (90.0) 12 (70.6) GC + MMF 2 (6.7) 5 (29.4) CNI n (%) 4 (13.33) 6 (35.29) 1.951 0.163 HCQ n (%) 16 (53.33) 8 (47.06) 0.171 0.679 Blood purification therapy n (%) 2 (6.67) 2 (11.76) 0.613 GC, glucorcorticoid; CTX, cyclophosphamide; MMF, mycophenolate mofetil; CNI, Calcineurin inhibitors; HCQ, hydroxychloroquine 3. Belimumab treatment: Seventeen enrolled cases of LN had a course of 2 weeks to 3 months of belimumab therapy, with an average of 1.9 ± 1.4 months. Fourteen patients completed 52 weeks of treatment, whereas the remaining three received belimumab for 12–20 weeks. 4. Validity 1)Activity: The SLEDAI-2000 score was comparable between the two groups at 6 months of treatment, whereas at 12 months, the belimumab group had a lower score; however, the difference between the groups was not statistically significant. Comparing the complement C3 and C4 levels, the belimumab group recovered faster than the traditional treatment group at 3, 6, and 12 months of treatment (P < 0.05). There were no differences in the titer changes of anti-double-stranded DNA antibodies between the two treatment groups (Fig. 1 ). 2) There were no significant differences in 24-h urine protein quantification and eGFR between the two groups after 3, 6, and 12 months of treatment (P > 0.05) (Fig. 2 ). 3) Renal response rate: At 6 months of treatment, the CR rate of all patients was 37/47 (78.7%), with that in the belimumab group (88.2%) being higher than that in the traditional treatment group (73.3%). The PR and NR rates were lower in the belimumab group than in the traditional treatment group; however, the difference was not statistically significant. At 12 months of treatment, the CR rate of all patients was 40/44 (90.9%), and there was no significant difference in the CR or PR rates between the two groups. There were no unrelieved cases in either group. Recurrence and end-stage renal disease: median follow-up of 13.0 months (9.0, 28.0 months) in the belimumab group, with no clinical recurrence cases (χ 2 = 1.061, P = 0.303). At 12 months of treatment, there were four cases (13.3%) of recurrence in the traditional treatment group, all of whom were followed up on time and treated regularly. As of October 31, 2023, the median follow-up time for all children in the traditional treatment group was 49.5 months (16.5, 70.0 months), of which 13 cases (43.3%) had 21 relapses, all within 5 years. The median time from onset to the first recurrence was 2 years (1, 3.5 years). Ten patients (76.9%) had one recurrence, one (7.7%) had two relapses, one (7.7%) had three relapses, and one (7.7%) had six relapses. Thirteen of the 21 relapses (61.9%) occurred after infection, fatigue, and irregular medication use, whereas eight (38.1%) had no triggers. At the end of follow-up, 16 patients in the traditional treatment group had become adults, of which one patient had developed stage 2 of end-stage renal disease (followed up for 116 months, with six relapses), whereas the other patients showed continuous CR. Further details are presented in Table 3 . Table 3 Comparison of SLE activity and renal response rates between the traditional treatment and the belimumab groups at 6 and 12 months of treatment 6 month 12 month Traditional treatment group Belimumab group t/Z/χ 2 P Traditional treatment group Belimumab group t/Z/χ 2 P SLEDAI-2000 4 (2,8) 4 (2,7) –0.255 0.799 4 (1,6) 0(0,4) –1.507 0.132 eGFR (mL/min.1.73 m 2 ) 128.65 ± 26.33 121.72 ± 21.96 0.863 0.394 116.80 ± 20.90 115.36 ± 18.32 0.196 0.846 Renal remission rate n (%) 1.631 0.442 0.094 0.759 CR 22 (73.3) 15 (88.2) 27 (90.0) 13 (92.9) PR 7 (23.3) 2 (11.8) 3 (10.0) 1 (7.1) NR 1 (3.3) 0 (0.0) 0 (0.0) 0 (0.0) Recurrence rate within 1 year n (%) 4 (13.3%) 0 (0.0%) 1.061 0.303 SLE, Systemic Lupus Erythematosus; SLEDAI-2000, Systemic Lupus Erythematosus Disease Activity Index-2000; eGFR, estimated glomerular filtration rate; CR, complete remission; NR, no renal remission; PR, partial remission Glucocorticoid dosage: Both groups were treated with sufficient glucocorticoids following the guidelines [ 6 ] to induce remission. After 6 months of treatment, the steroid dosage in the belimumab group (17.87 ± 6.96 mg/d) was significantly lower than that in the traditional treatment group (27.33 ± 8.40 mg/d) (P < 0.001). The hormone dose in the belimumab group (10.00 (5.3, 10.0) mg/d) after 12 months of treatment was significantly lower than that in the traditional treatment group (13.75 (10.0,22.5) mg/d) (P = 0.007), with significant statistical significance. See Fig. 3 for details 5) Safety: No infusion-related reactions occurred in any patient during belimumab administration. Nine children (52.9%) experienced acute upper respiratory tract infections two to four times, one (5.9%) had gastroenteritis, one (5.9%) had tinea versicolor, and one (5.9%) had a varicella zoster virus infection. Notably, all infections improved within 1 week, and no serious adverse reactions occurred. There was a downward trend in serum immunoglobulin M (IgM), IgG, and IgA levels compared with baseline at 6 and 12 months after administering belimumab; however, there was no statistically significant difference (Table 4 ). Table 4 Comparison of immunoglobulin levels in the belimumab group baseline 6 month 12 month F P IgG (g/L) 8.65 ± 4.60 7.52 ± 3.21 7.16 ± 2.97 0.669 0.517 IgM (g/L) 1.26 ± 0.47 0.95 ± 0.40 0.93 ± 0.37 2.955 0.063 IgA (g/L) 0.83 ± 0.42 0.56 ± 0.30 0.64 ± 0.38 2.18 0.125 IG, immunoglobulin Discussion Standardized treatment with corticosteroids combined with immunosuppressive agents (including CTX or MMF) improves renal prognosis, but it is not an ideal therapy. According to adult data, approximately 45% of patients with proliferative LN do not improve within 6 months of standard treatment [ 8 ], and 25–30% develop end-stage kidney disease (ESKD) within 20 years [ 9 ]. A cohort study of adults with LN in the UK [ 10 ] showed that 33% of patients with histologically confirmed grade III or IV LN experienced renal recurrence at an average of 3.5 years after induction, 44% of patients with PR experienced renal recurrence. The recurrence rate was only 5% among patients who achieved initial CR. Subsequent studies [1.12] also suggest that an inadequate renal response to induction therapy primarily causes recurrence and poor prognosis. Compared with adults, there are few reports on pediatric LN. In recent long-term prognostic data on pediatric LN, survival rates without advanced chronic kidney disease (CKD), ESKD, or death were 92.7% and 83.2% at 10 and 20 years, respectively [ 13 ]. Proliferative LN is the most common and severe type of LN in children [ 14 – 15 ] and is a risk factor for progression to CKD [ 16 ]. Recurrence is common in children, especially those aged < 13 years [ 17 ]. In this study, proliferative LN accounted for 97.6% of the cases involving the kidneys. We evaluated the renal response rates at 6 and 12 months of induction therapy, with CR rates of 78.7% and 90.9% and PR rates of 19.1% and 9.1%, respectively. Notably, both were higher than previous literature reports, which indicated that only 40–60% of children achieved a CR at 6 months of induction therapy [ 7 ]; however, our data showed that 43.3% of children in the traditional treatment group experienced recurrence within 5 years after remission, which is close to the recent data from children with LN in Hong Kong, China (recurrence rate of 41%) [ 13 ] and the United States (recurrence rate of 46%) [ 18 ]. In this study, 61.9% of relapses occurred after infection, fatigue, or irregular medication use. The 2017 European Children's LN Evidence-Based Recommendation [ 19 ] also indicated that the noncompliance rate in children's treatment was as high as 50%. Notably, some children with long-term glucocorticoid use experienced different degrees of negative effects on their psychology, growth, and development due to Cushing syndrome, infection, diabetes, hypertension, ocular hypertension, and other adverse reactions [ 20 ], which led to a decline in compliance with the standard treatment scheme. Therefore, to achieve and maintain sustained renal remission, reduce long-term exposure to glucocorticoids and infections, and improve treatment compliance, it is equally crucial to prevent recurrence and improve prognosis. Previous studies have shown elevated serum BAFF levels are associated with SLE pathogenesis, supporting the basic principle of targeted molecular therapy for SLE. Research on BAFF blockade therapy for childhood LN remains limited; however, multiple randomized trials of non-renal SLE have shown that the efficacy and safety of belimumab are comparable in pediatric and adult patients [ 21 – 22 ]. This study analyzed the efficacy and safety of the early use of belimumab combined with standard traditional regimens for treating active LN. Seventeen patients were included in this study. After a median follow-up of 13 months, the belimumab group was compared with 30 patients with LN treated only with standard regimens. It was observed that the belimumab group had a higher SLEDAI score (23.59 ± 7.78 vs. 19.13 ± 6.10) at enrollment and a higher median urinary protein level (75.9 mg/kg. d vs. 63.3 mg/kg. d) and renal pathological activity index (10.47 ± 2.72 vs. 9.59 ± 2.78). The statistical results showed a higher renal remission rate and a 1-year recovery rate in both groups; however, there was no difference in the incidence rate; the renal remission rate of the belimumab group was slightly higher than that of the traditional treatment group (88.2% vs. 73.3% in June and 92.9% vs. 90.0% in December). There was no recurrence at 1 year, which was significantly lower than that in the traditional treatment group (13.3%). This indicates that belimumab may effectively reduce disease activity and maintain LN remission without recurrence. However, in this study, the median recurrence time for children in the traditional treatment group was 2 years. In contrast, the follow-up time for the belimumab group was still short, and the number of enrolled cases was not large. Consequently, whether belimumab can maintain long-term non-recurrence in patients still requires a larger sample size and extended follow-up time to further observe the long-term efficacy of belimumab. Similarly, our data showed that, under similar conditions of renal remission, the dose of glucocorticoids used in the belimumab group was significantly lower than that used in the traditional treatment group at 6 and 12 months of treatment, which is consistent with a recent observational study of 17 real-world studies on using belimumab in patients with SLE. The reduction in SLEDAI score, prednisone equivalent dose, and recurrence frequency was significant within 6–12 months of belimumab treatment [ 23 ]. Belimumab is a recombinant whole human monoclonal antibody that inhibits the survival of autoreactive B cells and promotes their apoptosis. It has a relatively small impact on advanced B cells, as it can retain a certain level of immunity. In this study, we also compared the serum levels of immunoglobulins, such as IgM, IgG, and IgA, during belimumab therapy. There was a downward trend compared with the baseline; however, no serious adverse reactions were observed clinically. In this multicenter, open-label study on the safety and efficacy of belimumab combined with standard therapy in treating patients with SLE for 13 years [ 24 ], the total exposure time of belimumab was 2294 patient-years, with an average median infusion frequency of 115.5 times. The results showed that with the extension of the observation years, the serum IgG levels of most patients (65.9%) were normal, with only 4.1% of patients experiencing a grade 3 decrease in IgG (250–399 mg/dL) and 2.4% reaching grade 4 (< 250 mg/dL). There was an average decrease of 16.2% in the IgG levels; however, the risk of infection, including severe infections, did not increase. Therefore, the long-term safety of belimumab was acceptable. At present, the timing and duration of belimumab treatment in children with LN remain unclear. However, it is unanimously believed that BAFF inhibition is a favorable complementary treatment based on existing traditional treatments for proliferative LN. This study has the following limitations: single-center design, small sample size, retrospective design, risk of data collection and recording bias, the short application time of belimumab, and lack of long-term follow-up data. Therefore, data from multiple centers and large sample sizes are required to improve this study’s statistical reliability and accuracy. Simultaneously, the follow-up period should be extended to observe belimumab’s long-term efficacy and safety in children with LN. This would provide further guidance for clinical decision-making and help determine the best timing and duration of administration and appropriate patient selection. In conclusion, with an equivalent renal remission rate, belimumab combined with the standard traditional regimen can reduce the dosage of glucocorticoids. The incidence of adverse events is low and generally in control. Abbreviations BAFF, B cell-activating factor CKD, chronic kidney disease CR, Complete remission CTX, cyclophosphamide ESKD, end-stage kidney disease Ig, immunoglobulin LN, lupus nephritis MMF, mycophenolate mofetil NR, no renal remission PR, partial remission SLE, Systemic lupus erythematosus UPCR, urine protein: creatinine ratio Declarations Funding :The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests : The authors declare no competing interests. Author contributions :Material preparation and data collection were performed by Huarong Li and Hongxian Yang; data analysis and revision were performed by Huarong Li and Chaoying Chen and Juan Tu; The frst draft of the manuscript was written by Huarong Li. All authors contributed to the study conception, design, and revision. All authors read and approved the fnal manuscript. Ethics approval :This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Beijing Capital Pediatric Research Institute in China [SHERLL2021052] Consent to participate :Informed consent obtained from parents and participants in the study. Data availability statements :The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. References Pan L, Liu J, Liu C et al. Childhood-onset systemic lupus erythematosus: characteristics and the prospect of glucocorticoid pulse therapy (2023). Front Immunol 14:1128754. https://doi.org/10.3389/fimmu.2023.1128754 Oni L, Wright RD, Marks S, Beresford MW, Tullus K (2021) Kidney outcomes for children with lupus nephritis. Pediatr Nephrol 36(6):1377–1385. https://doi.org/10.1007/s00467-020-04686-1. Epub 2020 Jul 28 Wenderfer SE, Chang JC, Goodwin Davies A, et al (2022) Using a multi-institutional pediatric learning health system to identify systemic lupus erythematosus and lupus nephritis: development and validation of computable phenotypes. Clin J Am Soc Nephrol 17(1):65–74. https://doi.org/10.2215/CJN.07810621. Epub 2021 Nov 3 Canny SP, Jackson SW (2021) B cells in systemic lupus erythematosus: from disease mechanisms to targeted therapies. Rheum Dis Clin North Am 47(3):395–413. https://doi.org/10.1016/j.rdc.2021.04.006 Aringer M, Costenbader K, Daikh D, et al. (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 78(9):1151–1159. https://doi.org/10.1136/annrheumdis-2018-214819. Epub 2019 Aug 5 Subspecialty Group of Renal Diseases, the Society of Pediatrics, Chinese Medical Association The Nephrology Group of the Pediatric Branch of the Chinese Medical Association Evidence based guidelines for the diagnosis and treatment of lupus nephritis (2018). Zhonghua Er Ke Za Zhi 56(2):88–94. https://doi.org/10.3760/cma.j.issn.0578-1310.2018.02.003 Demir S, Gülhan B, Özen S, et al (2022) Long-term renal survival of paediatric patients with lupus nephritis. Nephrol Dial Transplant 37(6):1069–1077. https://doi.org/10.1093/ndt/gfab152 Smith EMD, Lythgoe H, Midgley A, Beresford MW, Hedrich CM (2019) Juvenile-onset systemic lupus erythematosus: update on clinical presentation, pathophysiology and treatment options. Clin Immunol 209:108274. https://doi.org/10.1016/j.clim.2019.108274. Epub 2019 Oct 31 Parikh SV, Rovin BH (2016) Current and emerging therapies for lupus nephritis. J Am Soc Nephrol 27(10):2929–2939. https://doi.org/10.1681/ASN.2016040415. Epub 2016 Jun 9 Hui M, Garner R, Rees F, et al (2013) Lupus nephritis: a 15-year multi-centre experience in the UK. Lupus 22(3):328–332. https://doi.org/10.1177/0961203312474084. Epub 2013 Feb 5 Yo JH, Barbour TD, Nicholls K (2019) Management of refractory lupus nephritis: challenges and solutions. Open Access Rheumatol 12(11):179–188. https://doi.org/10.2147/OARRR.S166303. eCollection Hanaoka H, Yamada H, Kiyokawa T, et al (2017) Lack of partial renal response by 12 weeks after induction therapy predicts poor renal response and systemic damage accrual in lupus nephritis class III or IV(J). Arthritis Res Ther 19(1):4. https://doi.org/10.1186/s13075-016-1202-z Chan EY, Yap DY, Wong WT, et al (2023) Long-term outcomes of children and adolescents with biopsy-proven childhood-onset lupus nephritis. Kidney Int Rep 8(1):141–150. https://doi.org/10.1016/j.ekir.2022.10.014. eCollection 2023 Jan. Groot N, de Graeff N, Avcin T, et al (2017) European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis 76(11):1788–1796. https://doi.org/10.1136/annrheumdis-2016-210960. Epub 2017 Jun 19 Kaneko M, Jackson SW (2023) Recent advances in immunotherapies for lupus nephritis. Pediatr Nephrol 38(4):1001–1012. https://doi.org/10.1007/s00467-022-05670-7. Epub 2022 Jul 1 Sakamoto AP, Silva CA, Islabão AG, et al (2023) Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus. Pediatr Nephrol 38(6):1843–1854. https://doi.org/10.1007/s00467-022-05811-y. Epub 2022 Nov 21 Chan EY, Yap DY, Wong WH, et al (2023) Renal relapse in children and adolescents with childhood-onset lupus nephritis: a 20-year study. Rheumatol (Oxf Engl) 26:kead447. https://doi.org/10.1093/rheumatology/kead447. Epub ahead of print Wenderfer SE, Orjuela A, Bekheirnia MR, et al. (2022) Lupus nephritis, autoantibody production and kidney outcomes in males with childhood-onset systemic lupus erythematosus. Pediatr Rep 14(2):220–232. https://doi.org/10.3390/pediatric14020030 Fiorot FJ, Islabão AG, Pereira RM, et al. (2019) Childhood-onset systemic lupus erythematosus group. Disease presentation of 1312 childhood-onset systemic lupus erythematosus: influence of ethnicity. Clin Rheumatol 38(10):2857–2863. https://doi.org/10.1007/s10067-019-04631-0. Epub 2019 Jun 13 Heshin-Bekenstein M, Trupin L, Yelin E, et al (2019) Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus. Semin Arthritis Rheum 49(2):267–272. https://doi.org/10.1016/j.semarthrit.2019.05.010. Epub 2019 Jun 3 Brunner HI, Abud-Mendoza C, Mori M, et al (2021) Efficacy and safety of Belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open 7(3):e001747. https://doi.org/10.1136/rmdopen-2021-001747 Brunner HI, Abud-Mendoza C, Viola DO, et al (2020) Safety and efficacy of intravenous Belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. Ann Rheum Dis 79(10):1340–1348. https://doi.org/10.1136/annrheumdis-2020-217101. Epub 2020 Jul 22 Huang SP, Snedecor SJ, Nanji S, Lloyd E, Bell CF (2022) Real-world effectiveness of Belimumab in systemic lupus erythematosus: A systematic literature review. Rheumatol Ther 9(4):975–991. https://doi.org/10.1007/s40744-022-00454-9. Epub 2022 May 21 Wallace DJ, Ginzler EM, Merrill JT, et al (2019) Safety and efficacy of Belimumab plus standard therapy for UP to thirteen years in patients with systemic lupus erythematosus. Arthritis Rheumatol 71(7):1125–1134. https://doi.org/10.1002/art.40861. Epub 2019 Jun 5 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 28 Jun, 2024 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 02 May, 2024 Reviews received at journal 20 Apr, 2024 Reviews received at journal 08 Apr, 2024 Reviewers agreed at journal 08 Apr, 2024 Reviewers agreed at journal 07 Apr, 2024 Reviewers agreed at journal 07 Apr, 2024 Reviewers invited by journal 07 Apr, 2024 Editor assigned by journal 02 Apr, 2024 Submission checks completed at journal 02 Apr, 2024 First submitted to journal 01 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4199333","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":289439891,"identity":"22029b2e-8a19-49d3-98e0-e7a86875ffaa","order_by":0,"name":"Huarong Li","email":"","orcid":"","institution":"Children’s Hospital Affiliated to Capital Institute of Pediatrics","correspondingAuthor":false,"prefix":"","firstName":"Huarong","middleName":"","lastName":"Li","suffix":""},{"id":289439892,"identity":"550c5516-55e4-4bc3-84d4-b0fe1c10615a","order_by":1,"name":"Chaoying Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYDACCSBmbAASzCBOBZscG3vzARK0WJzhM+bjOZZApBYQqGyTS5wnkaOAVwf/7OZjD37usJMzOM57+MWNM2bpbQw5DAw/KrbhtuTOsXTD3jPJxgaH+dIsZ1Sk5bYxnD3A2HPmNk4tBhI5ZtKMbcyJGw7zmBlLnDmW28bYl8DM2IZPS/43oJZ6iJa/bf/T2Zh5DAhoyWEDajkM0mL8QLKNLYGNjYAWiRtpZpK9bceNJYG2MEicYTNs42FLOIjPL/wzkp9J/GyrluM7f8b4AzAq5eXnPz744EcFbi1woHCAgU0CxjlAWD0QyDcwMH8gSuUoGAWjYBSMOAAAtKNWmhgptY0AAAAASUVORK5CYII=","orcid":"","institution":"Children’s Hospital Affiliated to Capital Institute of Pediatrics","correspondingAuthor":true,"prefix":"","firstName":"Chaoying","middleName":"","lastName":"Chen","suffix":""},{"id":289439893,"identity":"30004cd4-2b4a-486d-9b4e-88ef42218f40","order_by":2,"name":"Hongxian Yang","email":"","orcid":"","institution":"Children’s Hospital Affiliated to Capital Institute of Pediatrics","correspondingAuthor":false,"prefix":"","firstName":"Hongxian","middleName":"","lastName":"Yang","suffix":""},{"id":289439894,"identity":"bf985005-0580-4c00-a695-06baaf44057d","order_by":3,"name":"Juan Tu","email":"","orcid":"","institution":"Children’s Hospital Affiliated to Capital Institute of Pediatrics","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Tu","suffix":""}],"badges":[],"createdAt":"2024-04-01 08:38:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4199333/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4199333/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-024-05662-9","type":"published","date":"2024-06-28T17:13:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54446134,"identity":"7498028b-edc9-4aed-a232-b96cb7bc85e1","added_by":"auto","created_at":"2024-04-10 16:20:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24098,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in complement C3/C4/anti dsDNA antibodies in the traditional treatment and belimumab groups\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4199333/v1/92feccb91439694f5970d3eb.jpg"},{"id":54446133,"identity":"3e9d7f4a-ff27-4a8c-9beb-87c0422b81f8","added_by":"auto","created_at":"2024-04-10 16:20:22","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28718,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in urinary protein and eGFR in the traditional treatment group and belimumab group\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4199333/v1/17cd71051de727b78b0971f7.jpg"},{"id":54446132,"identity":"ee03dc59-f604-45e4-987e-f9130bfa1eff","added_by":"auto","created_at":"2024-04-10 16:20:22","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15965,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of glucocorticoid doses between the traditional treatment and belimumab groups at 6 and 12 months of treatment\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4199333/v1/a5f99023317b075605a72dd3.jpg"},{"id":59288184,"identity":"50b9ccd5-aa6f-4cab-a0e4-e50fe8f9a78e","added_by":"auto","created_at":"2024-06-28 17:13:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":614728,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4199333/v1/93ce209a-0e2d-44a8-ba2a-81611a04343c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of belimumab combined with the standard regimen in treating children with lupus nephritis","fulltext":[{"header":"What is Known","content":"\u003cp\u003e\u0026bull;Belimumab\u0026nbsp;is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026bull; Due to the paucity of studies, its efects and side efects in children with LN remain unclear.\u003c/p\u003e\n\u003cp\u003eWhat is New:\u003c/p\u003e\n\u003cp\u003e\u0026bull;\u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis was a single-center, retrospective cohort study\u0026nbsp;evaluated\u0026nbsp;the efficacy and safety of belimumab combined with the standard regimen in treating children with\u0026nbsp;proliferative LN.\u003c/p\u003e\n\u003cp\u003e\u0026bull; With an equivalent renal remission rate, belimumab combined with the standard traditional regimen can reduce the dosage of glucocorticoids. The incidence of adverse events is low and generally in control.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSystemic lupus erythematosus (SLE) is an autoimmune disease that invades multiple organs and systems. Childhood-onset SLE accounts for only 15\u0026ndash;20% of all SLE cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]; however, it is more acute, affects more systems, has a more active course, and has a worse prognosis than adult SLE, especially in patients with kidney involvement. Consequently, over 50% of children with SLE develop lupus nephritis (LN) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], usually within the first 2 years of diagnosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The standard induction regimen of corticosteroids combined with immunosuppressants, including cyclophosphamide (CTX) or mycophenolate mofetil (MMF), has improved the renal prognosis; however, over one-third of children may still experience recurrence after remission [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eBelimumab can bind to B cell-activating factor (BAFF) (also known as B lymphocyte stimulator, Blys) with high affinity. It blocks Blys from binding to receptors on B cells and inhibits B cell proliferation and plasma cell differentiation, thereby reducing the production of autoantibodies in the serum and thus treating SLE [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As the first biologic approved for SLE treatment in children aged\u0026thinsp;\u0026ge;\u0026thinsp;5, it was also approved on February 10, 2022, to be combined with conventional therapy for active LN in adults. However, research on the clinical application of belimumab in children with LN is limited. Therefore, we collected clinical data from patients with active LN who received belimumab combined with standard traditional regimens at our center. We aimed to evaluate the efficacy and safety of belimumab in this population and provide a reference for its clinical application in pediatrics.\u003c/p\u003e"},{"header":"Materials and Method","content":"\u003cp\u003eResearch participants\u003c/p\u003e \u003cp\u003eThis single-center, retrospective cohort study collected the clinical data of newly diagnosed patients with active LN hospitalized in the nephrology department between December 2004 and February 2023.\u003c/p\u003e \u003cp\u003eGrouping\u003c/p\u003e \u003cp\u003eThe participants were divided into belimumab and traditional treatment groups based on whether or not they received belimumab treatment.\u003c/p\u003e \u003cp\u003e(1) Traditional treatment: All patients were administered glucocorticoids or immunosuppressants. The immunosuppressants included CTX, MMF, cyclosporine A, and tacrolimus. The specific treatment plans are provided in the guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and were determined based on the patient's condition.\u003c/p\u003e \u003cp\u003e(2) The treatment regimen of belimumab was an intravenous infusion of 10 mg/kg at weeks 0, 2, and 4, followed by another intravenous infusion of 10 mg/kg every 4 weeks for a maximum duration of 52 weeks.\u003c/p\u003e \u003cp\u003eObservation and evaluation indicators\u003c/p\u003e \u003cp\u003e(1) Data on sex, age, LN course, clinical and pathological classification, and extrarenal-affected organs in the two groups of children at the time of enrollment and follow-up were collected through outpatient follow-up visits and readmission medical records or phone calls after discharge.\u003c/p\u003e \u003cp\u003e(2) Observation indicators: Laboratory indicators of patients at 0, 6, and 12 months after treatment included 24-h urine protein output and estimated glomerular filtration rate (eGFR) based on the Schwartz formula.\u003c/p\u003e \u003cp\u003e(3) Effectiveness evaluation: Indicators such as renal remission rate, recurrence rate, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score, and glucocorticoid dosage at 6 and 12 months of treatment were evaluated.\u003c/p\u003e \u003cp\u003e(4) Safety evaluation: During the follow-up period of belimumab treatment, adverse events, including infusion reactions, hypersensitivity reactions, infections, and blood immunoglobulin levels, were recorded.\u003c/p\u003e \u003cp\u003eTreatment response [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1) Complete remission (CR): Normal renal function (eGFR\u0026thinsp;\u0026gt;\u0026thinsp;90 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e), proteinuria\u0026thinsp;\u0026lt;\u0026thinsp;0.5 g/d or urine protein: creatinine ratio (UPCR)\u0026thinsp;\u0026lt;\u0026thinsp;0.5 mg/mg\u003c/p\u003e \u003cp\u003e(2) Partial remission (PR): renal function is stable, and proteinuria is reduced by \u0026gt;\u0026thinsp;50% from baseline.\u003c/p\u003e \u003cp\u003e(3) No renal remission (NR): failure to achieve partial or complete remission within 6\u0026ndash;12 months of therapy.\u003c/p\u003e \u003cp\u003e(4) Recurrence: In patients with complete remission, proteinuria increased by \u0026gt;\u0026thinsp;50%, and/or GFR decreased by \u0026gt;\u0026thinsp;25% from baseline.\u003c/p\u003e \u003cp\u003eStatistical methods\u003c/p\u003e \u003cp\u003eSPSS 26 software was used for statistical analysis, and the count data were presented as the number of cases (percentage). Intergroup comparison was applied: χ2 tests or Fisher's exact probability method. If the measurement data conforms to a normal distribution, it is expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and a t-test is used for intergroup comparison. However, the Mann\u0026ndash;Whitney U rank sum test is used for intergroup comparison of non-normally distributed econometric data represented as M (1/4, 3/4). Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e1. General information:\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eForty-seven cases were enrolled, with a median age of 11.0 years (9.0, 12.0 years), including 18 males (38.3%) and 29 females (61.7%). In the traditional treatment group, there were 30 cases with a median age of 10.5 years (8.75, 12.0 years), including 13 males (43.3%) and 17 females (56.7%). The initial diagnosis was between December 2004 and April 2022. The belimumab group had 17 cases, with a median age of 11.0 years (9.0, 13.0 years), including five males (29.4%) and 12 females (70.6%). The initial diagnoses were made between September 2020 and February 2023.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e2. Clinical manifestations and treatment:\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e1) Extrarenal manifestations: At disease onset, there were no statistically significant differences between the two groups regarding the extrarenal organs involved, including the skin, mucosa, musculoskeleton, blood, nervous system, and complement C3/C4 levels. The SLEDAI-2000 score in the belimumab group (23.59\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78) was higher than that in the traditional treatment group (19.13\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10), with statistical significance (t\u0026thinsp;=\u0026thinsp;2.176, P\u0026thinsp;=\u0026thinsp;0.035).\u003c/p\u003e\n\u003cp\u003e2) Renal changes: The two groups had no significant differences in pyuria, gross hematuria, 24-h urine protein content, or eGFR. Among all cases, acute nephritis (16/47, 34.0%) and nephrotic syndrome (23/47, 48.9%) were the most common, and there was no statistically significant difference in clinical subtype distribution between both groups (\u0026chi;2\u0026thinsp;=\u0026thinsp;2.192, P\u0026thinsp;=\u0026thinsp;0.533). Forty-two pediatric patients underwent renal tissue biopsy, of which 41 (97.6%) were type III (including type III\u0026thinsp;+\u0026thinsp;V) and type IV (including type IV\u0026thinsp;+\u0026thinsp;V), with type IV being the most common. There was no statistically significant difference in pathological subtype distribution between both groups (\u0026chi;2\u0026thinsp;=\u0026thinsp;4.441, P\u0026thinsp;=\u0026thinsp;0.35). The belimumab group\u0026rsquo;s average activity index (10.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72) was higher than that of the traditional treatment group (9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78). However, there was no statistically significant difference (t\u0026thinsp;=\u0026thinsp;0.935, P\u0026thinsp;=\u0026thinsp;0.357), and the median chronic index between both groups was not statistically different (Z\u0026thinsp;=\u0026thinsp;1.244, P\u0026thinsp;=\u0026thinsp;0.322) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of baseline clinical and laboratory data between the traditional treatment group and the belimumab group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTraditional treatment group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBelimumab group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003et/Z/\u0026chi;\u003csup\u003e2\u003c/sup\u003e值\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale (n %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.345\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.10\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;0.989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.328\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOrgan involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMucocutaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14 (46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emusculoskeletal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (23.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.931\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematologic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNervous system\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKidney\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGross hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14 (46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.716\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePyuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (76.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.805\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUTP (mg/kg.d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.3 (22.3,146.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.9(34.5,117.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.894\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScr (umol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.54 (48.5,74.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65.50(49.5,102.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;0.831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.406\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eeGFR (mL/min.1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e94.72\u0026thinsp;\u0026plusmn;\u0026thinsp;32.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.02\u0026thinsp;\u0026plusmn;\u0026thinsp;37.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical typing (n %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.533\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematuria proteinuria type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNephrotic syndrome type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (23.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAcute nephritis type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14 (46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAcute progressive nephritis type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (3.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePathological classification (n %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.441\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅣ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (76.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (88.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅢ+Ⅴ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eⅣ+Ⅴ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;0.935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0 (0.0.1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0 (0.0.0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;1.244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC3 (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.27 (0.2,0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.32 (0.2,0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;0.444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.657\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC4 (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.04 (0.0,0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06 (0.0,0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.489\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSLEDAI-2000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19.13\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.59\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026ndash;2.176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eUTP, Uridine-5\u0026prime;-triphosphate; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; SLEDAI-2000, Systemic Lupus Erythematosus Disease Activity Index-2000\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eImmune induction therapy: Among the two groups, CTX was the most commonly used immunosuppressive induction therapy, with 39 cases. Among them, the traditional treatment and belimumab groups had 27 (93.10%) and 12 cases (70.59%), respectively; joint calcineurin inhibitor class (\u0026chi;2\u0026thinsp;=\u0026thinsp;1.951, P\u0026thinsp;=\u0026thinsp;0.163) and hydroxychloroquine (\u0026chi;2\u0026thinsp;=\u0026thinsp;0.171, P\u0026thinsp;=\u0026thinsp;0.679) but there was no difference in treatment between the two groups. Four children were treated with blood purification, including two continuous bedside blood filtration, one peritoneal dialysis, and one plasma exchange (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of induction therapy between the traditional treatment and belimumab groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTraditional treatment group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBelimumab group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmune induction therapy n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGC\u0026thinsp;+\u0026thinsp;CTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27 (90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12 (70.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGC\u0026thinsp;+\u0026thinsp;MMF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCNI n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (13.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (35.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.951\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHCQ n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (53.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (47.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood purification therapy n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (6.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (11.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.613\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eGC, glucorcorticoid; CTX, cyclophosphamide; MMF, mycophenolate mofetil; CNI, Calcineurin inhibitors; HCQ, hydroxychloroquine\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e3. Belimumab treatment:\u003c/p\u003e\n\u003cp\u003eSeventeen enrolled cases of LN had a course of 2 weeks to 3 months of belimumab therapy, with an average of 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 months. Fourteen patients completed 52 weeks of treatment, whereas the remaining three received belimumab for 12\u0026ndash;20 weeks.\u003c/p\u003e\n\u003cp\u003e4. Validity\u003c/p\u003e\n\u003cp\u003e1)Activity: The SLEDAI-2000 score was comparable between the two groups at 6 months of treatment, whereas at 12 months, the belimumab group had a lower score; however, the difference between the groups was not statistically significant. Comparing the complement C3 and C4 levels, the belimumab group recovered faster than the traditional treatment group at 3, 6, and 12 months of treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There were no differences in the titer changes of anti-double-stranded DNA antibodies between the two treatment groups (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e2) There were no significant differences in 24-h urine protein quantification and eGFR between the two groups after 3, 6, and 12 months of treatment (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e3) Renal response rate: At 6 months of treatment, the CR rate of all patients was 37/47 (78.7%), with that in the belimumab group (88.2%) being higher than that in the traditional treatment group (73.3%). The PR and NR rates were lower in the belimumab group than in the traditional treatment group; however, the difference was not statistically significant. At 12 months of treatment, the CR rate of all patients was 40/44 (90.9%), and there was no significant difference in the CR or PR rates between the two groups. There were no unrelieved cases in either group.\u003c/p\u003e\n\u003cp\u003eRecurrence and end-stage renal disease: median follow-up of 13.0 months (9.0, 28.0 months) in the belimumab group, with no clinical recurrence cases (\u0026chi; 2\u0026thinsp;=\u0026thinsp;1.061, P\u0026thinsp;=\u0026thinsp;0.303). At 12 months of treatment, there were four cases (13.3%) of recurrence in the traditional treatment group, all of whom were followed up on time and treated regularly. As of October 31, 2023, the median follow-up time for all children in the traditional treatment group was 49.5 months (16.5, 70.0 months), of which 13 cases (43.3%) had 21 relapses, all within 5 years. The median time from onset to the first recurrence was 2 years (1, 3.5 years). Ten patients (76.9%) had one recurrence, one (7.7%) had two relapses, one (7.7%) had three relapses, and one (7.7%) had six relapses. Thirteen of the 21 relapses (61.9%) occurred after infection, fatigue, and irregular medication use, whereas eight (38.1%) had no triggers. At the end of follow-up, 16 patients in the traditional treatment group had become adults, of which one patient had developed stage 2 of end-stage renal disease (followed up for 116 months, with six relapses), whereas the other patients showed continuous CR. Further details are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of SLE activity and renal response rates between the traditional treatment and the belimumab groups at 6 and 12 months of treatment\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e6 month\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e12 month\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTraditional treatment group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBelimumab group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et/Z/\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTraditional treatment group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBelimumab group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003et/Z/\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSLEDAI-2000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (2,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (2,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ndash;0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (1,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ndash;1.507\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eeGFR (mL/min.1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e128.65\u0026thinsp;\u0026plusmn;\u0026thinsp;26.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e121.72\u0026thinsp;\u0026plusmn;\u0026thinsp;21.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.863\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e116.80\u0026thinsp;\u0026plusmn;\u0026thinsp;20.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e115.36\u0026thinsp;\u0026plusmn;\u0026thinsp;18.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.846\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRenal remission rate n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (73.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (88.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (92.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecurrence rate within 1 year n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.303\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eSLE, Systemic Lupus Erythematosus; SLEDAI-2000, Systemic Lupus Erythematosus Disease Activity Index-2000; eGFR, estimated glomerular filtration rate; CR, complete remission; NR, no renal remission; PR, partial remission\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eGlucocorticoid dosage: Both groups were treated with sufficient glucocorticoids following the guidelines [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] to induce remission. After 6 months of treatment, the steroid dosage in the belimumab group (17.87\u0026thinsp;\u0026plusmn;\u0026thinsp;6.96 mg/d) was significantly lower than that in the traditional treatment group (27.33\u0026thinsp;\u0026plusmn;\u0026thinsp;8.40 mg/d) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The hormone dose in the belimumab group (10.00 (5.3, 10.0) mg/d) after 12 months of treatment was significantly lower than that in the traditional treatment group (13.75 (10.0,22.5) mg/d) (P\u0026thinsp;=\u0026thinsp;0.007), with significant statistical significance. See Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e for details\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e5) Safety: No infusion-related reactions occurred in any patient during belimumab administration. Nine children (52.9%) experienced acute upper respiratory tract infections two to four times, one (5.9%) had gastroenteritis, one (5.9%) had tinea versicolor, and one (5.9%) had a varicella zoster virus infection. Notably, all infections improved within 1 week, and no serious adverse reactions occurred. There was a downward trend in serum immunoglobulin M (IgM), IgG, and IgA levels compared with baseline at 6 and 12 months after administering belimumab; however, there was no statistically significant difference (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cbr\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of immunoglobulin levels in the belimumab group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e6 month\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e12 month\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIgG (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.669\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIgM (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.955\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIgA (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eIG, immunoglobulin\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eStandardized treatment with corticosteroids combined with immunosuppressive agents (including CTX or MMF) improves renal prognosis, but it is not an ideal therapy. According to adult data, approximately 45% of patients with proliferative LN do not improve within 6 months of standard treatment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and 25\u0026ndash;30% develop end-stage kidney disease (ESKD) within 20 years [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A cohort study of adults with LN in the UK [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] showed that 33% of patients with histologically confirmed grade III or IV LN experienced renal recurrence at an average of 3.5 years after induction, 44% of patients with PR experienced renal recurrence. The recurrence rate was only 5% among patients who achieved initial CR. Subsequent studies [1.12] also suggest that an inadequate renal response to induction therapy primarily causes recurrence and poor prognosis.\u003c/p\u003e \u003cp\u003eCompared with adults, there are few reports on pediatric LN. In recent long-term prognostic data on pediatric LN, survival rates without advanced chronic kidney disease (CKD), ESKD, or death were 92.7% and 83.2% at 10 and 20 years, respectively [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Proliferative LN is the most common and severe type of LN in children [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and is a risk factor for progression to CKD [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Recurrence is common in children, especially those aged\u0026thinsp;\u0026lt;\u0026thinsp;13 years [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this study, proliferative LN accounted for 97.6% of the cases involving the kidneys. We evaluated the renal response rates at 6 and 12 months of induction therapy, with CR rates of 78.7% and 90.9% and PR rates of 19.1% and 9.1%, respectively. Notably, both were higher than previous literature reports, which indicated that only 40\u0026ndash;60% of children achieved a CR at 6 months of induction therapy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]; however, our data showed that 43.3% of children in the traditional treatment group experienced recurrence within 5 years after remission, which is close to the recent data from children with LN in Hong Kong, China (recurrence rate of 41%) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and the United States (recurrence rate of 46%) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this study, 61.9% of relapses occurred after infection, fatigue, or irregular medication use. The 2017 European Children's LN Evidence-Based Recommendation [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] also indicated that the noncompliance rate in children's treatment was as high as 50%. Notably, some children with long-term glucocorticoid use experienced different degrees of negative effects on their psychology, growth, and development due to Cushing syndrome, infection, diabetes, hypertension, ocular hypertension, and other adverse reactions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], which led to a decline in compliance with the standard treatment scheme. Therefore, to achieve and maintain sustained renal remission, reduce long-term exposure to glucocorticoids and infections, and improve treatment compliance, it is equally crucial to prevent recurrence and improve prognosis.\u003c/p\u003e \u003cp\u003ePrevious studies have shown elevated serum BAFF levels are associated with SLE pathogenesis, supporting the basic principle of targeted molecular therapy for SLE. Research on BAFF blockade therapy for childhood LN remains limited; however, multiple randomized trials of non-renal SLE have shown that the efficacy and safety of belimumab are comparable in pediatric and adult patients [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This study analyzed the efficacy and safety of the early use of belimumab combined with standard traditional regimens for treating active LN. Seventeen patients were included in this study. After a median follow-up of 13 months, the belimumab group was compared with 30 patients with LN treated only with standard regimens. It was observed that the belimumab group had a higher SLEDAI score (23.59\u0026thinsp;\u0026plusmn;\u0026thinsp;7.78 vs. 19.13\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10) at enrollment and a higher median urinary protein level (75.9 mg/kg. d vs. 63.3 mg/kg. d) and renal pathological activity index (10.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72 vs. 9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78). The statistical results showed a higher renal remission rate and a 1-year recovery rate in both groups; however, there was no difference in the incidence rate; the renal remission rate of the belimumab group was slightly higher than that of the traditional treatment group (88.2% vs. 73.3% in June and 92.9% vs. 90.0% in December). There was no recurrence at 1 year, which was significantly lower than that in the traditional treatment group (13.3%). This indicates that belimumab may effectively reduce disease activity and maintain LN remission without recurrence. However, in this study, the median recurrence time for children in the traditional treatment group was 2 years. In contrast, the follow-up time for the belimumab group was still short, and the number of enrolled cases was not large.\u003c/p\u003e \u003cp\u003eConsequently, whether belimumab can maintain long-term non-recurrence in patients still requires a larger sample size and extended follow-up time to further observe the long-term efficacy of belimumab. Similarly, our data showed that, under similar conditions of renal remission, the dose of glucocorticoids used in the belimumab group was significantly lower than that used in the traditional treatment group at 6 and 12 months of treatment, which is consistent with a recent observational study of 17 real-world studies on using belimumab in patients with SLE. The reduction in SLEDAI score, prednisone equivalent dose, and recurrence frequency was significant within 6\u0026ndash;12 months of belimumab treatment [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBelimumab is a recombinant whole human monoclonal antibody that inhibits the survival of autoreactive B cells and promotes their apoptosis. It has a relatively small impact on advanced B cells, as it can retain a certain level of immunity. In this study, we also compared the serum levels of immunoglobulins, such as IgM, IgG, and IgA, during belimumab therapy. There was a downward trend compared with the baseline; however, no serious adverse reactions were observed clinically. In this multicenter, open-label study on the safety and efficacy of belimumab combined with standard therapy in treating patients with SLE for 13 years [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], the total exposure time of belimumab was 2294 patient-years, with an average median infusion frequency of 115.5 times. The results showed that with the extension of the observation years, the serum IgG levels of most patients (65.9%) were normal, with only 4.1% of patients experiencing a grade 3 decrease in IgG (250\u0026ndash;399 mg/dL) and 2.4% reaching grade 4 (\u0026lt;\u0026thinsp;250 mg/dL). There was an average decrease of 16.2% in the IgG levels; however, the risk of infection, including severe infections, did not increase. Therefore, the long-term safety of belimumab was acceptable.\u003c/p\u003e \u003cp\u003eAt present, the timing and duration of belimumab treatment in children with LN remain unclear. However, it is unanimously believed that BAFF inhibition is a favorable complementary treatment based on existing traditional treatments for proliferative LN.\u003c/p\u003e \u003cp\u003eThis study has the following limitations: single-center design, small sample size, retrospective design, risk of data collection and recording bias, the short application time of belimumab, and lack of long-term follow-up data. Therefore, data from multiple centers and large sample sizes are required to improve this study\u0026rsquo;s statistical reliability and accuracy. Simultaneously, the follow-up period should be extended to observe belimumab\u0026rsquo;s long-term efficacy and safety in children with LN. This would provide further guidance for clinical decision-making and help determine the best timing and duration of administration and appropriate patient selection.\u003c/p\u003e \u003cp\u003eIn conclusion, with an equivalent renal remission rate, belimumab combined with the standard traditional regimen can reduce the dosage of glucocorticoids. The incidence of adverse events is low and generally in control.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBAFF, B cell-activating factor\u003c/p\u003e\n\u003cp\u003eCKD, chronic kidney disease\u003c/p\u003e\n\u003cp\u003eCR, Complete remission\u003c/p\u003e\n\u003cp\u003eCTX, cyclophosphamide\u003c/p\u003e\n\u003cp\u003eESKD, end-stage kidney disease\u003c/p\u003e\n\u003cp\u003eIg, immunoglobulin\u003c/p\u003e\n\u003cp\u003eLN, lupus nephritis\u003c/p\u003e\n\u003cp\u003eMMF, mycophenolate mofetil\u003c/p\u003e\n\u003cp\u003eNR, no renal remission\u003c/p\u003e\n\u003cp\u003ePR, partial remission\u003c/p\u003e\n\u003cp\u003eSLE, Systemic lupus erythematosus\u003c/p\u003e\n\u003cp\u003eUPCR, urine protein: creatinine ratio\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e:Material preparation and data collection were performed by \u0026nbsp;Huarong Li and Hongxian Yang; data analysis and revision were performed by Huarong Li and Chaoying Chen and Juan Tu; The frst draft of the manuscript was written by Huarong Li. All authors contributed to the study conception, design, and revision. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e:This study was approved by the Ethics Committee of the Children\u0026apos;s Hospital Affiliated to Beijing Capital Pediatric Research Institute in China [SHERLL2021052]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e:Informed consent obtained from parents and participants in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statements\u003c/strong\u003e:The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePan L, Liu J, Liu C et al. Childhood-onset systemic lupus erythematosus: characteristics and the prospect of glucocorticoid pulse therapy (2023). Front Immunol 14:1128754. https://doi.org/10.3389/fimmu.2023.1128754\u003c/li\u003e\n\u003cli\u003eOni L, Wright RD, Marks S, Beresford MW, Tullus K (2021) Kidney outcomes for children with lupus nephritis. Pediatr Nephrol 36(6):1377\u0026ndash;1385. https://doi.org/10.1007/s00467-020-04686-1. Epub 2020 Jul 28\u003c/li\u003e\n\u003cli\u003eWenderfer SE, Chang JC, Goodwin Davies A, et al (2022) Using a multi-institutional pediatric learning health system to identify systemic lupus erythematosus and lupus nephritis: development and validation of computable phenotypes. Clin J Am Soc Nephrol 17(1):65\u0026ndash;74. https://doi.org/10.2215/CJN.07810621. Epub 2021 Nov 3\u003c/li\u003e\n\u003cli\u003eCanny SP, Jackson SW (2021) B cells in systemic lupus erythematosus: from disease mechanisms to targeted therapies. Rheum Dis Clin North Am 47(3):395\u0026ndash;413. https://doi.org/10.1016/j.rdc.2021.04.006\u003c/li\u003e\n\u003cli\u003eAringer M, Costenbader K, Daikh D, et al. (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 78(9):1151\u0026ndash;1159. https://doi.org/10.1136/annrheumdis-2018-214819. Epub 2019 Aug 5\u003c/li\u003e\n\u003cli\u003eSubspecialty Group of Renal Diseases, the Society of Pediatrics, Chinese Medical Association The Nephrology Group of the Pediatric Branch of the Chinese Medical Association Evidence based guidelines for the diagnosis and treatment of lupus nephritis (2018). Zhonghua Er Ke Za Zhi 56(2):88\u0026ndash;94. https://doi.org/10.3760/cma.j.issn.0578-1310.2018.02.003\u003c/li\u003e\n\u003cli\u003eDemir S, G\u0026uuml;lhan B, \u0026Ouml;zen S, et al (2022) Long-term renal survival of paediatric patients with lupus nephritis. Nephrol Dial Transplant 37(6):1069\u0026ndash;1077. https://doi.org/10.1093/ndt/gfab152\u003c/li\u003e\n\u003cli\u003eSmith EMD, Lythgoe H, Midgley A, Beresford MW, Hedrich CM (2019) Juvenile-onset systemic lupus erythematosus: update on clinical presentation, pathophysiology and treatment options. Clin Immunol 209:108274. https://doi.org/10.1016/j.clim.2019.108274. Epub 2019 Oct 31\u003c/li\u003e\n\u003cli\u003eParikh SV, Rovin BH (2016) Current and emerging therapies for lupus nephritis. J Am Soc Nephrol 27(10):2929\u0026ndash;2939. https://doi.org/10.1681/ASN.2016040415. Epub 2016 Jun 9\u003c/li\u003e\n\u003cli\u003eHui M, Garner R, Rees F, et al (2013) Lupus nephritis: a 15-year multi-centre experience in the UK. Lupus 22(3):328\u0026ndash;332. https://doi.org/10.1177/0961203312474084. Epub 2013 Feb 5\u003c/li\u003e\n\u003cli\u003eYo JH, Barbour TD, Nicholls K (2019) Management of refractory lupus nephritis: challenges and solutions. Open Access Rheumatol 12(11):179\u0026ndash;188. https://doi.org/10.2147/OARRR.S166303. eCollection\u003c/li\u003e\n\u003cli\u003eHanaoka H, Yamada H, Kiyokawa T, et al (2017) Lack of partial renal response by 12 weeks after induction therapy predicts poor renal response and systemic damage accrual in lupus nephritis class III or IV(J). Arthritis Res Ther 19(1):4. https://doi.org/10.1186/s13075-016-1202-z\u003c/li\u003e\n\u003cli\u003eChan EY, Yap DY, Wong WT, et al (2023) Long-term outcomes of children and adolescents with biopsy-proven childhood-onset lupus nephritis. Kidney Int Rep 8(1):141\u0026ndash;150. https://doi.org/10.1016/j.ekir.2022.10.014. eCollection 2023 Jan.\u003c/li\u003e\n\u003cli\u003eGroot N, de Graeff N, Avcin T, et al (2017) European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis 76(11):1788\u0026ndash;1796. https://doi.org/10.1136/annrheumdis-2016-210960. Epub 2017 Jun 19\u003c/li\u003e\n\u003cli\u003eKaneko M, Jackson SW (2023) Recent advances in immunotherapies for lupus nephritis. Pediatr Nephrol 38(4):1001\u0026ndash;1012. https://doi.org/10.1007/s00467-022-05670-7. Epub 2022 Jul 1\u003c/li\u003e\n\u003cli\u003eSakamoto AP, Silva CA, Islab\u0026atilde;o AG, et al (2023) Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus. Pediatr Nephrol 38(6):1843\u0026ndash;1854. https://doi.org/10.1007/s00467-022-05811-y. Epub 2022 Nov 21\u003c/li\u003e\n\u003cli\u003eChan EY, Yap DY, Wong WH, et al (2023) Renal relapse in children and adolescents with childhood-onset lupus nephritis: a 20-year study. Rheumatol (Oxf Engl) 26:kead447. https://doi.org/10.1093/rheumatology/kead447. Epub ahead of print\u003c/li\u003e\n\u003cli\u003eWenderfer SE, Orjuela A, Bekheirnia MR, et al. (2022) Lupus nephritis, autoantibody production and kidney outcomes in males with childhood-onset systemic lupus erythematosus. Pediatr Rep 14(2):220\u0026ndash;232. https://doi.org/10.3390/pediatric14020030\u003c/li\u003e\n\u003cli\u003eFiorot FJ, Islab\u0026atilde;o AG, Pereira RM, et al. (2019) Childhood-onset systemic lupus erythematosus group. Disease presentation of 1312 childhood-onset systemic lupus erythematosus: influence of ethnicity. Clin Rheumatol 38(10):2857\u0026ndash;2863. https://doi.org/10.1007/s10067-019-04631-0. Epub 2019 Jun 13\u003c/li\u003e\n\u003cli\u003eHeshin-Bekenstein M, Trupin L, Yelin E, et al (2019) Longitudinal disease- and steroid-related damage among adults with childhood-onset systemic lupus erythematosus. Semin Arthritis Rheum 49(2):267\u0026ndash;272. https://doi.org/10.1016/j.semarthrit.2019.05.010. Epub 2019 Jun 3\u003c/li\u003e\n\u003cli\u003eBrunner HI, Abud-Mendoza C, Mori M, et al (2021) Efficacy and safety of Belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open 7(3):e001747. https://doi.org/10.1136/rmdopen-2021-001747\u003c/li\u003e\n\u003cli\u003eBrunner HI, Abud-Mendoza C, Viola DO, et al (2020) Safety and efficacy of intravenous Belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. Ann Rheum Dis 79(10):1340\u0026ndash;1348. https://doi.org/10.1136/annrheumdis-2020-217101. Epub 2020 Jul 22\u003c/li\u003e\n\u003cli\u003eHuang SP, Snedecor SJ, Nanji S, Lloyd E, Bell CF (2022) Real-world effectiveness of Belimumab in systemic lupus erythematosus: A systematic literature review. Rheumatol Ther 9(4):975\u0026ndash;991. https://doi.org/10.1007/s40744-022-00454-9. Epub 2022 May 21\u003c/li\u003e\n\u003cli\u003eWallace DJ, Ginzler EM, Merrill JT, et al (2019) Safety and efficacy of Belimumab plus standard therapy for UP to thirteen years in patients with systemic lupus erythematosus. Arthritis Rheumatol 71(7):1125\u0026ndash;1134. https://doi.org/10.1002/art.40861. Epub 2019 Jun 5\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Lupus nephritis, children, Belimumab, Efficacy, Safety","lastPublishedDoi":"10.21203/rs.3.rs-4199333/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4199333/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis was a single-center, retrospective cohort study. We collected the clinical data of children with newly active LN hospitalized in the Department of Nephrology between December 2004 and February 2023. The children were divided into belimumab and traditional treatment groups according to whether they received belimumab or not. The renal remission rate, recurrence rate, and glucocorticoid dose were compared between both groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e1) Baseline data of clinical and pathology: 47 children with a median age of 11 years were enrolled in this study, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ±7.78) was higher than that for those in the traditional treatment group (19.13 ±6.10) (\u003cem\u003e\u003cstrong\u003et\u003c/strong\u003e\u003c/em\u003e=2.176, \u003cem\u003eP\u003c/em\u003e=0.035). The two groups showed no significant difference in pyuria, gross hematuria, 24-h urinary protein, and estimated glomerular filtration rate. In all cases, acute glomerulonephritis (34.0%) and nephrotic syndrome (48.9%) were the most common, and there were no differences in the clinical classification between both groups (χ2=2.192, \u003cem\u003eP\u003c/em\u003e=0.533). Forty-two children completed renal biopsy, and there were no differences in the distribution of pathological classification and the activity and chronic indices between both groups (\u003cstrong\u003eχ\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e=\u003c/strong\u003e4.441, \u003cem\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/em\u003e=0.35; \u003cstrong\u003et\u003c/strong\u003e\u003cem\u003e=\u003c/em\u003e0.935, \u003cem\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e=\u003c/em\u003e0.357; \u003cstrong\u003eZ\u003c/strong\u003e=1.244, \u003cem\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e=\u003c/em\u003e0.322).\u003c/p\u003e\n\u003cp\u003e2) Efficacy: The complement C3/C4 in the belimumab group was faster than that in the traditional treatment group 3, 6, and 12 months after treatment (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). The average SLEDAI-2000 score showed no difference in both groups at 6 and 12 months (\u003cem\u003eP\u003c/em\u003e=0.799; \u003cem\u003eP\u003c/em\u003e=0.132). There were no differences in the complete remission rate between both groups at 6 months and 12 months (χ2=1.631, \u003cem\u003eP\u003c/em\u003e=0.442; χ2=0.094, \u003cem\u003eP\u003c/em\u003e=0.759). The 1-year recurrence rate was 13.3% in the traditional treatment group, and there was no clinical recurrence in the belimumab group (χ2=1.061, \u003cem\u003eP\u003c/em\u003e=0.303). Furthermore, 6 months after treatment, the glucocorticoid dose in the belimumab group (17.87 ±6.96 mg/d) was significantly lower than that in the traditional treatment group (27.33 ±8.40 mg/d) (\u003cem\u003eP\u003c/em\u003e=0.000). At 12 months of treatment, the glucocorticoid dose in the belimumab group [10.00 (5.3) mg/d] was also significantly lower than that in the traditional treatment group [13.75 (10.0) mg/d] (\u003cem\u003ep\u003c/em\u003e=0.007).\u003c/p\u003e\n\u003cp\u003e3) Safety: there was no infusion reaction during belimumab treatment. Nine cases (52.9%) had two to four episodes of acute upper respiratory tract infections, one (5.9%) had gastroenteritis, one (5.9%) had tinea versicolor, and one (5.9%) had a varicella-zoster virus infection. The infection was relieved within 1 week without serious adverse reactions. During belimumab therapy, the levels of serum immunoglobulin M (IgM), IgG, and IgA showed a decreasing trend at 6 and 12 months compared with baseline, but there was no statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eWith an equivalent renal remission rate, belimumab combined with the standard traditional regimen can reduce the dosage of glucocorticoids. The incidence of adverse events is low and generally in control.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of belimumab combined with the standard regimen in treating children with lupus nephritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-10 16:20:14","doi":"10.21203/rs.3.rs-4199333/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-02T20:19:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-20T17:27:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-08T12:32:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20accfbd-45ec-49e3-807f-371c9f9d6a19","date":"2024-04-08T11:18:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6db2a65a-ef7b-4d12-9eeb-4463134367b6","date":"2024-04-08T03:29:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"454a7e93-d991-4cd7-9d16-47fe87534f36","date":"2024-04-07T21:10:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-07T20:49:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-02T07:33:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-02T07:32:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2024-04-01T08:37:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a5e1fd2b-038d-41e6-9d52-972f9b18b6a9","owner":[],"postedDate":"April 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-06-28T17:13:00+00:00","versionOfRecord":{"articleIdentity":"rs-4199333","link":"https://doi.org/10.1007/s00431-024-05662-9","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2024-06-28 17:13:00","publishedOnDateReadable":"June 28th, 2024"},"versionCreatedAt":"2024-04-10 16:20:14","video":"","vorDoi":"10.1007/s00431-024-05662-9","vorDoiUrl":"https://doi.org/10.1007/s00431-024-05662-9","workflowStages":[]},"version":"v1","identity":"rs-4199333","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4199333","identity":"rs-4199333","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}