| Systemic lupus erythematosus（SLE）is an autoimmune disease characterized by the presence of multiple autoantibodies in the plasma and the involvement of multiple organ systems.B lymphocyte stimulator（BLy S）,also known as the B cell activating factor of the TNF family（BAFF）,is a key factor in the pathogenesis of SLE.B lymphocyte stimulator（BLy S）,also known as the B cell activating factor of the TNF family（BAFF）,can be activated by binding transmembrane activator and CAML[calcium-modulator and cyclophilin ligand]interactor（TACI）,B cell B cell maturation antigen（BCMA）and BLy S receptor 3（B lymphocyte stimulator receptor,BR3）play a regulatory role in the promotion of B cell survival and maturation plasmacytosis.Studies have shown that BLy S is overexpressed in SLE patients[2].belimumab（BLM）,a human immunoglobulin（Ig）G1λκmonoclonal antibody targeting BLy S,selectively inhibits the binding of BLy S to survival receptors on B cells and inhibits the survival and differentiation of aberrantly activated self-reactive B cells.BLM has been approved as add-on therapy for patients with mild to moderately active SLE who have failed conventional treatment regimens,as it improves the rate of induced remission,reduces relapses and reduces hormone use.The recommended dosing regimen is 10mg/kg every 2 weeks for the first 3 doses and every 4 weeks thereafter.However,BLM has a slow onset of action and it is recommended that 6 months after treatment be used as the time point to determine whether BLM is effective.No clinical studies have been conducted to determine whether there is a difference in clinical remission,hormone reduction and safety between loading doses and non-loading doses of a slow-acting add-on treatment for mild to moderate SLE patients who have failed to respond to conventional treatment.This study is intended to compare the efficacy and safety of BLM loading doses（10mg/kg given every 2 weeks for the first 3 doses and every 4 weeks thereafter）with non-loading doses（10mg/Kg given every 4weeks）for the induction of remission in SLE patients.Purpose:The aim of this study was to evaluate the efficacy and safety of comparing loading and non-loading doses of BLM for the induction of remission in SLE patients and to examine the differences in B-cell subpopulations in SLE patients after the application of loading doses of BLM and non-loading doses of BLM anti-treatment,respectively,using flow cytometry.This provides new clinical research evidence for the appropriate use of doses of BLM to induce and maintain remission of SLE treatment.Methods:The study included patients aged 18-75 years with a definite diagnosis of SLE who presented to our rheumatology department between February 2022 and December 2022.Patients with SLE who had a Systemic lupus erythematosus disease activity index（SLEDAI）score of≥8.A total of 48 patients with SLE were randomised in a 1:2 ratio to the BLM loading dose group（intravenous BLM 10mg/kg every 2 weeks for the first three doses,then every 4 weeks until week 24）and the non-loading group（intravenous BLM 10mg/Kg every 4weeks until week 24）.Combined conventional treatment.Follow-up points were set at baseline,4 weeks,12 weeks and 24 weeks respectively.Data were collected on clinical presentation,laboratory tests,in vitro B-cell subsets,SRI-4 response index and adverse effects of treatment to compare the efficacy and safety of the non-load dose BLM and load dose groups.Results:1.16 and 32 patients with SLE treated with loading dose and non-loading dose were included in the study.Compared to baseline,SLEDAI scores decreased by≥4 points in both loading dose and non-loading dose groups at 24 weeks of BLM treatment[8.00（8.00,11.50）vs.2.00（2.00,7.50）,P<0.001]and[8.00（8.00.10.00）vs 4.00（2.00,4.00）,P<0.001],a statistically significant difference;PGA scores decreased significantly（2.23±0.53 vs 0.43±0.23,P<0.001）and（2.14±0.69 vs 0.46±0.24,P<0.001）;there were no new A grades or more than 1 new B grade score at 24 weeks of treatment in either group of BILAG or more than 1 new B grade score at 24 weeks of treatment,with no statistically significant difference before and after treatment（P>0.05）.Compared to baseline,at 24 weeks of BLM treatment,complement C3（0.22±0.08 vs 0.38±0.15,P<0.001）,（0.28±0.15 vs 0.37±0.14,P<0.05）,and complement C4（0.17±0.07 vs 0.35±0.21,P<0.05）in the loading dose and non-loading dose groups,（0.18±0.12 vs 0.24±0.12,P<0.001）were significantly increased;anti-ds-DNA antibodies were significantly decreased[167.79（106.10,470.37）vs 46.18（26.47,87.64）,P<0.05],[112.16（89.42,239.83）vs 42.27（22.45.85.04）,P<0.001];the number of CD19+B cells both decreased（851.81±133.05 vs 492.71±134.55,P<0.001）,（842.65±115.51 vs 487.92±122.86,P<0.001）,with statistically significant differences;the number of CD19+CD10-CD269+B cells decreased[15.10（6.80,20.15）vs 14.15（4.60,19.35）,P>0.05],[14.35（6.48,25.43）vs 13.95（4.76,19.87）,P>0.05],but the differences were not statistically significant.2.1)Comparison of SRI-4 compliance rates between the loading dose and non-loading dose groups at week 12 and 24 of treatment:the SRI-4 compliance rate was higher in the loading dose group than in the non-loading dose group at week 12 of treatment,but the difference was not statistically significant（56.25%vs.46.87%,P>0.05）;the SRI-4compliance rates were similar in the two groups at week 24 of treatment（68.75%vs.65.62%,P>0.05）.2.2)The proportion of patients on prednisone or equivalent hormone≥7.5 mg/d at24 weeks of treatment was significantly lower in both the loading dose and non-loading dose groups compared to baseline（93.73%vs 43.75%,P<0.05）and（87.50%vs 59.38%,P<0.05）.At 24 weeks of treatment,the proportion of patients on prednisone or equivalent hormone≥7.5mg/d was statistically significantly lower in the loading dose group than in the non-loading dose group（43.75%vs.59.38%,P<0.05）;at 24 weeks of treatment,the mean cumulative hormone dose was lower in the loading dose group than in the non-loading dose group,with a statistically significant difference between the two groups（3021.82mg/d vs.3081.67mg/d）.2.3)The differences in SLEDAI,PGA,BILAG,anti-ds-DNA antibody,complement C3,CD19+B cell count and CD19+CD10-CD269+B cell count between the two groups at weeks 4,12 and 24 of treatment were not statistically significant（P>0.05）;the differences between the loading dose and non-loading dose groups at week 4,12 and 24 of treatment were not statistically significant（P>0.05）.complement C4 at week 4 and 12 were（0.30±0.14 vs 0.22±0.16,P<0.05）and（0.36±0.18 vs 0.27±0.21,P<0.05）in the two groups of loading dose,respectively.3.Comparing the safety aspects between the two groups,there were no serious adverse events in the loading dose and non-loading dose groups at 24 weeks of treatment.Both groups had no serious adverse events in infusion reactions（6.25%vs 3.13%,P>0.05）,upper respiratory tract infection（6.25%vs 0.00%,P>0.05）,urinary tract infection（0.00%vs3.13%,P>0.05）,headache（6.25%vs 0.00%,P>0.05）,insomnia（6.25%vs 0.00%,P>0.05）,muscle pain（6.25%vs 0.00%,P>0.05）,diarrhea（12.50%vs 3.13%,P>0.05）,nausea（6.25%vs 0.00%,P>0.05）,skin rash（0.00%vs 3.13%,P>0.05）There was no statistically significant difference between groups in terms of adverse reactions.Conclusion:Both the loading and non-loading doses of BLM were effective in inducing clinical remission in patients with mild to moderately active SLE despite conventional treatment.The difference in SRI-4 attainment rates between the loading dose of BLM and the non-loading dose at 12 and 24 weeks of treatment was not statistically significant.add-on treatment with BLM had a slow onset of action and the loading dose did not significantly increase efficacy,onset of action or clinical remission attainment rates.However,the loading dose group achieved faster hormone reductions and reduced the mean cumulative hormone dosage.There was no difference in safety between the loading and non-loading doses. |
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