Network Meta-analysis Of Using Long-term Five Immunosuppressant Combined With Glucocorticoids In Treating LN

Objective: Systemic lupus erythematous(SLE)is a chronic autoimmune disease that can migrate to multiple systems.Lupus nephritis(LN)is one of the most serious complications of SLE.LN is one of the most serious complications of SLE,which has a great impact on the quality of life and long-term prognosis of patients.This study evaluated the efficacy and safety of long-term use of different immunosuppressive agents combined with glucocorticoids in the treatment of LN in order to guide clinical use.Methods: Searching Pub Med,Cochrane Library,Web of Science,EMbase,CNKI,Wanfang and CBM database,collect randomized controlled trials(RCT)of different immunosuppressant combined with glucocorticoids for LN.Evaluate the effectiveness and safety of different treatments for LN using general meta-analysis and network metaanalysis.Then network meta-analysis was performed using Win Bugs 1.4.3 and Stata 12.0 software.Results: A total 50 RCTs involving 4202 patients were included.1.Effectiveness:(1)General meta-analysis results showed that the cyclophosphamide + leflunomide and cyclophosphamide + mycophenolate group significantly reduced the level of urinary protein,and its MD(95% CI)was-0.60(-1.08,-0.12)and-0.39(-0.68,-0.11),respectively;Cyclophosphamide + leflunomide and cyclophosphamide + mycophenolate mofetil significantly reduced serum creatinine levels,with MD(95% CI)of-0.58(-1.06,-0.10)and-0.45(-0.85,-0.05),respectively;Cyclophosphamide + leflunomide and cyclophosphamide + mycophenolate mofetil significantly increased albumin levels,with MD(95% CI)of 1.20(0.69,1.71)and 0.54(0.21,0.86),respectively,compared with the cyclophosphamide group.(2)Network meta-analysis results showed that cyclophosphamide + mycophenolate mofetil and leflunomide were better than cyclophosphamide and tacrolimus in the treatment of LN for reducing the level of urinary protein.There was significant statistical differences(P<0.05).According to the results of surface under the cumulative ranking(SUCRA),cyclophosphamide + leflunomide and phosphoramide + mycophenolate mofetil were better in treating LN to reduce proteinuria,with the SUCRA were 75.3% and 63.4%,respectively.Cyclophosphamide + leflunomide and phosphoramide + mycophenolate mofetil were better in treating LN to reduce serum creatinine,with SUCRA and 75.9% and 63.7%,respectively.Cyclophosphamide and cyclophosphamide + mycophenolate mofetil were better in treating LN on increasing albumin,with SUCRA of 97.8% and 57.8%,respectively.Cyclophosphamide and cyclophosphamide + mycophenolate mofetil were better in treating LN on increasing C3,and their SUCRA are 88.9% and 62.0%,respectively.2.Safety:(1)General meta-analysis results showed that mycophenolate mofetil significantly reduced the risk of infection,with the RR(95% CI)was 0.50(0.36,0.70);Leflunomide and mycophenolate mofetil significantly reduced the risk of leukopenia,with the RR(95% CI)were 0.34(0.15,0.78)and 0.25(0.12,0.52),respectively;Mycophenolate mofetil significantly reduced the risk of menstrual disorders,with the RR(95% CI)was 0.16(0.06,0.43);Leflunomide,mycophenolate mofetil and Leflunomide+mycophenolate mofetil significantly reduced the risk of developing gastrointestinal reactions,with the RR(95% CI)were 0.29(0.18,0.46),0.39(0.29,0.53)and 0.28(0.11,0.71),respectively;Leflunomide and mycophenolate mofetil significantly reduced the risk of elevated transaminases,with the RR(95% CI)were 0.52(0.30,0.91)and 0.16(0.07,0.38),respectively,compared with the cyclophosphamide group.(2)Network meta-analysis results showed that mycophenolate mofetil,mycophenolate mofetil + cyclophosphamide had a lower risk of LN infection,with the SUCRA were 76.7% and 63.0%,respectively;The mycophenolate mofetil and leflunomide groups had a lower risk of developing transaminase elevation in LN,with the SUCRA were 96.7% and 54.7%,respectively.Conclusion: 1.Cyclophosphamide + leflunomide +GC and cyclophosphamide + mycophenolate mofetil +GC effectively improve LN condition,with reducing urine protein and serum creatinine,and increasing serum albumin;2.Leflunomide and mycophenolate mofetil +GC have a better safety,with less risk of LN infection,leukopenia,menstrual disorders,gastrointestinal reactions and elevated transaminases;3.Based on the results of network meta-analysis and SUCRA ranking,the effects of CTX+LEF+GC and CTX+MMF+GC on LN were superior to other drugs,which more worthy of clinical promotion.