title: Optimal drug regimens for primary biliary cirrhosis: a systematic review and network meta-analysis.
abstract: OBJECTIVE
  Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP), D-penicillamine (DPM), methotrexate (MTX), or azathioprine (AZP). Since the optimum treatment regimen remains inconclusive, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse event (AE).
  
  
  METHODS
  We searched PubMed, Embase, Scopus and the Cochrane Library for randomized controlled trials until August 2014. We estimated HRs for MOLT and ORs for AE. The sensitivity analysis based on dose of UDCA was also performed.
  
  
  RESULTS
  The search identified 49 studies involving 12 different treatment regimens and 4182 patients. Although no statistical significance can be found in MOLT, COT plus UDCA was ranked highest for efficacy outcome amongst all the treatment regimes. While for AEs, compared with OBS or UDCA, monotherapy with COC (OR 5.6, P < 0.001; OR 5.89, P < 0.001), CYP (OR 3.24, P < 0.001; OR 3.42, P < 0.001), DPM (OR 8.00, P < 0.001; OR 8.45, P < 0.001) and MTX (OR 5.31, P < 0.001; OR 5.61, P < 0.001) were associated with statistically significant increased risk of AEs. No significant differences were found for other combination regimes. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Consistently, in the sensitivity analysis, results closely resembled our primary analysis.
  
  
  CONCLUSIONS
  COT plus UDCA was the most efficacious among treatment regimens both for MOLT and AEs.
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Gui-Qi
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Renji School of Wenzhou Medical University, Wenzhou, China.
authors.forename: Gui-Qian
authors.initials: GQ
authors.lastname: Huang
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Li-Ren
authors.initials: LR
authors.lastname: Wang
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Renji School of Wenzhou Medical University, Wenzhou, China.
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhi-Rui
authors.initials: ZR
authors.lastname: Zhou
authors.affiliation: Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Braddock
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Zhou
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zheng
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D001629:Bezafibrate / Q000627:therapeutic use; D001652:Bile Ducts / Q000473:pathology; D003078:Colchicine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods*; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010396:Penicillamine / Q000627:therapeutic use; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D000305:Adrenal Cortex Hormones; D014580:Ursodeoxycholic Acid; D016572:Cyclosporine; D010396:Penicillamine; D001379:Azathioprine; D003078:Colchicine; D001629:Bezafibrate; D008727:Methotrexate
keywords: UDCA-based therapy; adverse events; indirect comparison; network meta-analysis; primary biliary cirrhosis