Clinical Observation And Literature Review Of Belimumab In The Treatment Of Lupus Nephritis

BackgroundSystemic lupus erythematosus(SLE)is a chronic autoimmune connective tissue disease that affects multiple organ systems.It is mainly characterized by the production of a large number of autoantibodies and the deposition of immune complexes in the body,mainly affecting women of reproductive age.Over the past 50 years,survival rates have improved dramatically because of early diagnosis and more appropriate treatment regimens.However,the standardized mortality rate for patients with SLE was still 4.6 times higher than for the general population.Lupus nephritis(LN),which occurs in 25%to 60%of patients with SLE,is one of the most serious clinical manifestations of SLE and is the leading cause of morbidity and mortality in SLE patients.In recent years,due to early diagnosis and the application of glucocorticoid combined with immunosuppressant therapy such as cyclophosphamide and mycophenolate mofetil,the survival rate of patients with LN has improved significantly.However,the proportion of patients with renal reactions is still very low,and there are many problems such as long maintenance remission period,poor targeting,high recurrence rate and many adverse reactions,which highlight the necessity of seeking better treatment options for LN.New drugs and treatment options are being explored continuously.Belimumab is a human monoclonal antibody that can specifically bind B-cell-activating factor,block its interaction with specific receptors,inhibit the survival and differentiation of B cells,and promote the apoptosis of B cells,so as to achieve the purpose of treating SLE.Belimumab was approved in 2011 for the treatment of active SLE patients who are positive for autoantibodies and receiving standard care.It is the first biologic agent approved by the U.S.Food and Drug Administration for active SLE.With the release of the results of a large randomized,double-blind,placebo-controlled phase Ⅲ trial(BLISS-LN)of belimumab in the treatment of active lupus nephritis in adults,the addition of belimumab to standard care is effective in improving renal outcome.Belimumab was approved by the Food and Drug Administration in 2020 for the treatment of adults with active LN,providing a new drug option for patients with LN.However,the efficacy and safety of beliliumab in Chinese patients with LN need to be further validated.ObjectiveTo investigate the efficacy and safety of belimumab in patients with active lupus nephritis.MethodsTen patients with active LN treated with belimumab in the Department of Nephrology and Rheumatology at Qilu Hospital of Shandong University from June 2020 to April 2021 were enrolled.Patients included in the study met the diagnostic criteria for LN,were positive for autoantibodies(antinuclear antibody titer≥1:80 and/or positive for anti-dsDNA antibodies),and had a SLEDAI-2K score≥6.Since the start of clinical observation,all patients were regularly treated with belimumab 10mg/kg intravenously,in combination with standard LN treatment,i.e.,oral prednisone(or methylprednisolone),hydroxychloroquine,and/or immunosuppressant therapy.Patients’ conditions were evaluated every four weeks,and relevant clinical data were collected:patients’ SLEDAI-2K score,urinary protein creatinine ratio,serum albumin,serum creatinine,complement(C3,C4),anti-dsDNA antibody levels,etc.At the same time,detailed medical history inquiry and physical examination,as well as the monitoring of urine routine,blood routine,liver and kidney function and other related laboratory indicators were conducted during the follow-up to count the incidence of adverse events after medication.Statistical software was used to conduct statistical analysis on the collected clinical data,and the differences of clinical indicators before and after treatment with belimumab were compared,so as to objectively evaluate the efficacy and safety of belimumab in the treatment of active lupus nephritis.ResultsA total of ten patients with active LN were included in this study,of which seven patients were included in the efficacy evaluation,and the other three patients were treated with belimumab for no more than 3 months and only included in the safety evaluation.Among the seven patients included in the efficacy evaluation in this study,the duration of treatment with belimumab was from 4 to 9 months,with a median treatment duration of 7 months.Among them,one patient(14.29%)achieved a complete remission,which was achieved by the eighth month after treatment,and three patients(42.86%)achieved a partial remission at the end of follow-up.With the extension of treatment time with belimumab,the total remission rate continued to increase.Overall proteinuria decreased from baseline at all follow-up time points,but only at 4 months(5.49±6.54g/g vs.3.61±6.04g/g,P=0.025)and 5 months(6.18±6.88g/g vs.3.03±4.88g/g,P=0.046)the decrease level of urinary protein was significantly different from baseline(P<0.05).The SLEDAI-2K score improved at all time points.During treatment,the levels of albumin,complement C3 and complement C4 increased,and the levels of anti-dsDNA antibodies decreased.In terms of safety,belimumab had a low incidence of adverse events,occurring in 2(20%)of the 10 patients with active LN included in the safety evaluation.One case is upper respiratory tract infection(10%)and the other is infusion reaction(10%).In addition,no death,severe infection,severe infusion reaction or hypersensitivity reaction,tumor,bone marrow suppression and other serious adverse events were found.ConclusionBelimumab had significant effect on LN,effectively reduced urinary protein and SLE disease activity,and the improvement of urinary protein and serological indexes increased gradually with the prolongation of treatment time.Belimumab has a low incidence of adverse events,besides,no death,serious infection,serious infusion reaction or hypersensitivity reaction,tumor,bone marrow suppression and other serious adverse events were found,with good safety.