| Backgrounds:Systemic lupus erythematosus(SLE)is an autoimmune disease that may affect multiple organ systems throughout the body,and lupus nephritis(LN)is one of the most common and severe organ manifestations of SLE.Refractory lupus nephritis(RLN)is defined as aggravation of renal injury at any time during the period of initial immunosuppressive therapy(increased SCr,increased proteinuria),or not achieving partial remission after at least 6 months of induction therapy.Previously common drugs used to treat LN patients mainly included glucocorticoids,hydroxychloroquine,and immunosuppressants such as cyclophosphamide,mycophenolate mofetil,calcineurin inhibitors.With the widespread application of the health management concept of early diagnosis and early treatment and the comprehensive treatment scheme of hormone combined with immunosuppressive agents,the survival rate of LN patients has improved,but the situation is still not optimistic.About 40%of LN patients cannot achieve renal remission,and the prognosis of RLN is even worse.Therefore,new therapeutic drugs have been continuously developed and applied,and a variety of biological agents targeting B lymphocytes have been proved to be effective in treating LN.Belimumab is a recombinant human IgG-lλ monoclonal antibody that can inhibit B-lymphocyte stimulator(BLyS),which can inhibit the abnormal activation,proliferation and differentiation of B lymphocytes,and alleviate the autoimmune reaction.The BLISS-LN trial,a phase 3,multicenter,randomized,double-blind,placebo-controlled trial for LN patients obtained positive results.Belimumab has been approved for the treatment of adults with active LN by the US Food and Drug Administration.However,there are still few studies on the treatment of RLN patients with belimumab,especially the effectiveness and safety of belimumab in Chinese RLN patients need to be further verified.Objectives:To evaluate the effectiveness and safety of belimumab combined with standard therapy in RLN.Methods:This was a retrospective,single-center study of RLN patients who received belimumab combined with standard therapy in the Department of Nephrology of Qilu Hospital of Shandong University from June 2020 to October 2022.The Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K)score,levels of the antinuclear antibody,anti-doublestranded DNA(anti-dsDNA)antibody,complement C3,complement C4,urinary protein-tocreatinine ratio(UPCR),serum albumin(Alb),blood urea nitrogen,serum creatinine(SCr)and estimated glomerular filtration rate(eGFR)were recorded at baseline and 1,2,3,4,5,6 and 12 months.Adverse events were recorded.Finally,the effectiveness and safety of belimumab were analyzed statistically.Results:This study involved 19 RLN patients,2 patients were evaluated for safety only,and 17 patients were evaluated for both effectiveness and safety.After treatment with belimumab combined with standard therapy,there were 8 patients(47.06%)achieved complete remission,2 patients(11.76%)achieved partial remission,and the total remission rate was 58.82%.The oral prednisone median daily dose(IQR)was reduced from 20.00(10.00-45.00)mg/day at baseline to 13.75(10.00-15.00)mg/day(P<0.01)at 6 months and 10.00(7.50-15.00)mg/d(P<0.01)at 12 months of treatment.Furthermore,clinical and laboratory indicators were also significantly improved after belimumab treatment,such as SLEDAI-2K score,UPCR,Alb,C3 and C4.The renal function estimated by eGFR was not obviously changed except the significant increase at 1 month.The safety profile of belimumab was outstanding,and only 3 patients(15.79%)occurred adverse events.Serious adverse events were not observed during treatment.Conclusions:Belimumab combined with standard therapy showed significant effectiveness and high safety profile of RLN in a real-life setting,which could reduce disease activity,proteinuria and oral glucocorticoid dose. |
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