title: Calcineurin inhibitors versus cyclophosphamide for idiopathic membranous nephropathy: A systematic review and meta-analysis of 21 clinical trials.
abstract: OBJECTIVE
  To compare the efficacy and safety of calcineurin inhibitors (CNIs) with cyclophosphamide (CTX) in the treatment of idiopathic membranous nephropathy (IMN).
  
  
  METHODS
  A literature search was carried out using PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and three Chinese databases (WanFang Data, Chongqing VIP and China National Knowledge Infrastructure) from inception through June 2016. Randomized controlled trials (RCTs) comparing the efficacy and safety of CNIs with CTX in IMN patients were included. Two authors independently extracted data and assessed the quality of each study. Statistical analyses were performed using Revman 5.3 software. Odds ratio (OR) for dichotomous data and mean difference (MD) for continuous data with 95% confidence interval (CI) were calculated and data were pooled with a random-effect model.
  
  
  RESULTS
  A total of twenty-one studies involving 1187 patients were included in this study. CNIs had significant merits in increasing total remission (CSA vs CTX: OR 1.91, 95%CI 1.09 to 3.34, P=0.02; TAC vs CTX: OR 2.95, 95%CI 1.84 to 4.75, P<0.00001), elevating serum albumin (CSA vs CTX: MD 3.83, 95%CI 2.49 to 5.16, P<0.00001; TAC vs CTX: OR 8.57, 95%CI 5.08 to 12.07, P<0.00001) and reducing proteinuria (CSA vs CTX: MD -0.73, 95%CI -1.25 to -0.22, P=0.005; TAC vs CTX: MD -1.7, 95%CI -2.29 to -1.10, P<0.00001) compared with CTX after 6months of treatment. However, no similar results were found after 12months. Moreover, CSA had a higher relapse rate than CTX (OR 3.89, 95%CI 1.53 to 9.92, P=0.004), which was not found in the comparison of TAC and CTX. The incidences of leukopenia, alopecia and liver damage were higher in the CTX group (OR (95%CI): 0.23 (0.09 to 0.59), 0.10 (0.04 to 0.24), and 0.36 (0.19 to 0.69, respectively), whereas the incidences of hirsutism, gingival hyperplasia, worsening hypertension and hyperuricemia were higher in the CSA group (OR (95%CI): 8.64 (1.97 to 37.79, 4.44 (1.09 to 17.99), 4.59 (1.43 to 14.82) and 9.05 (1.53 to 53.36), respectively).
  
  
  CONCLUSIONS
  Our systematic review demonstrates that CNIs are promising alternatives to CTX for IMN patients, primarily due to their better short-term efficacy and safety. Well-designed clinical trials are needed to further evaluate the long-term efficacy and safety of CNIs and CTX.
authors.affiliation: Department of pharmacy, Peking University Third Hospital, Beijing, China; School of basic medicine and clinical pharmacy, China pharmaceutical university, Nanjing, China.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Qiu
authors.affiliation: Department of pharmacy, Peking University Third Hospital, Beijing, China. Electronic address: laural.zhang@yahoo.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Zhao
authors.affiliation: Public health department, AixMarseille university, Marseille, France.
authors.forename: Jun Wen
authors.initials: JW
authors.lastname: Zhou
mesh_terms: D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: Calcineurin inhibitors; Cyclophosphamide; Idiopathic membranous nephropathy; Meta-analysis