Preliminary Evaluation Of Immunosuppressive Agents For The Maintence Treatment Of Lupus Nephritis

Objective: To evaluate the efficacy and safety of different kinds of immunosuppressive agents(mycophenolate,tacrolimus,azathioprine,leflunomide,cyclosporine,cyclophosphamide,tripterygium and multiple targets)for the maintenance treatment of lupus nephritis.Methods: The related RCTs in Chinese and English database,such as CNKI,CBM,PUBMED,Web of Science,EMBASE and Cochrane Library were searched from the date of their establishment to august 10,2018.Articles were searched according to the inclusion and exclusion criteria and were evaluated by the improved Jadad scale.Win BUGS 3.2.2 and Stata 14.0 were used to analysis the data in the article.Results: After strict selection by the evaluators,10 RCTs involving 936 patients were included in our review.Traditional head-to-head meta-analysis was performed on the included studies and there was no significant difference in relapse rate between azathioprine and mycophanate for the treatment of lupus nephritis(RR=1.39,95% CI 0.98 ~ 1.97,P > 0.05),there was no significant statistical difference in other interventions.Compared withazathioprine,the incidence of leukopenia in patients treated with tacrolimus was relatively low(95% CI 0.06~0.58,P=0.004).In terms of the incidence of infection,the results of mycophenolate compared with cyclophosphamide(95% CI 0.21 ~ 0.89,P=0.02)showed that the incidence of infection of cyclophosphamide was higher,comparison between azathioprine and cyclophosphamide(95% CI 0.22~0.93,P=0.03)showed that the infection rate of cyclophosphamide was higher.Regarding the incidence of menstrual disorder,a comparison of azathioprine with tripterygium(95% CI 0.07~0.77,P=0.02)indicated that azathioprine treatment was less likely to cause menstrual disorder,a comparison of leflunmide and tripterygium(95% CI0.02~0.35,P=0.0006)showed that menstrual disorder were more likely to occur during treatment with tripterygium.In terms of rash incidence,the comparison between leflunmide and tripterygium(95% CI 1.13 ~ 319.38,P=0.04)showed that leflunmide was more likely to result in rash.There was no significant statistical difference in other interventions about adverse effects.The results of net-work meta-analysis indicated that there was no significant difference in relapse rate between immunosuppressive agents.The possible ranking of relapse rate in descending order as follows: cyclophosphamide>tripterygium>leflunomide>azathioprine>cyclosporine>mycophenolate>multiple targets > tacrolimus.In terms of leukopenia,there was also no significant difference between the immunosuppressive agents.The possible ranking of incidence of leukopenia in ascending order as follows: tacrolimus< tripterygium < mycophenolate < cyclosporine < multiple targets <azathioprine<leflunomide<cyclophosphamide.Conclusion: There was no significant difference for direct comparison of different kinds of immunosuppressive agents for the maintenance therapy of lupus nephritis about relapse rate.In terms of safety,azathioprine has a higher incidence of leukopenia than tacrolimus,the incidence of cyclophosphamide infection was higher than that of mycophenolate and azathioprine,the incidence of menstrual disorders in tripterygium was higher than azathioprine and leflunomide,the rash of leflunomide was more common than tripterygium.The results of network analysis showed that there was no significant difference in relapse rate and leukopenia between immunosuppressive agents;tacrolimus was the most likely to have the lowest relapse rate and leukopenia,while cyclophosphamide was the most likely to have the highest relapse rate and leukopenia.