Risk Of Infection With Different Immunosuppressive Drugs Combined With Glucocorticoids For The Treatment Of Idiopathic Membranous Nephropathy:A Pairwise And Network Meta-analysis

IntroductionIdiopathic membranous nephropathy(IMN)is a common cause of nephrotic syndrome in adults and one of the leading causes of end-stage renal disease(ESRD).During recent years,the incidence of IMN has been increasing and becoming younger.The main treatment option for IMN is the use of immunosuppressive drugs combined with glucocorticoids(GC).However,the infection risk with different immunosuppressive drug treatments has not been systematically compared.Therefore,a network meta-analysis(NMA)was performed to compare the risk of infection of different immunosuppressive drug treatments for IMN.MethodsSearch all the randomized controlled trials(RCT)related to IMN treatment from the PubMed,EMBASE,Cochrane Library,Wanfang,CNKI and VIP databases,and further searches were made based on previous relevant reviews and references cited in meta-analysis.,thedeadline is May 21,2018.The traditional meta-analysis was performed using Rev Man 5.3 software to calculate the risk ratio(RR)and 95%confidence interval(CI)of the dichotomous data,and the random effect model was used to summarize the data.The NMA was performed using Stata 14.0 software,and the surface under the cumulative ranking area(SUCRA)was drawn to rank the infection risks of different interventions.ResultsA total of 38 RCTs with 2066 participants were included for comparison of nine interventions.Direct comparison revealed that tacrolimus combined with GC(TAC+GC)was associated with a significantly lower risk of infection than that with intravenous cyclophosphamide(IVCTX)+GC with a risk ratio(95% CI)of 0.52(0.34-0.79).The NMA showed that IVCTX+GC was associated with a significantly higher risk of infection than that with TAC+GC,cyclosporin(CSA)+GC,and oral cyclophosphamide(POCTX)+GC(IVCTX+GC vs.TAC+GC: RR=1.98,95% CI: 1.25-3.13;IVCTX+GC vs.CSA+GC:RR=3.35,95% CI: 1.31-8.55;POCTX+GC vs.IVCTX+GC: RR=0.39,95% CI: 0.20-0.76).A sensitivity analysis,excluding studies with a very long follow-up period showed that the risk of infection with non-immunosuppressive therapy was related to the length of follow-up,and no significant difference was found in other results..The SUCRA showed that CSA+GC had the lowest risk of infection(SUCRA 86.0%),and the second best treatment was POCTX+GC(SUCRA 78.6%).Conversely,IVCTX+GC(SUCRA 16.2%)had a higher risk of infection than that with the other immunosuppressive drugs.ConclusionsCSA+GC and POCTX+GC were associated with a lower risk of infection than that with other immunosuppressive drugs combined with GC for IMN.Combined with comparative efficacy data,these results can help patients make informed decisions about treatment options for IMN.