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Optimal drug regimens for primary biliary cirrhosis: a systematic review and network meta-analysis

2015; Impact Journals LLC; Volume: 6; Issue: 27 Linguagem: Inglês

10.18632/oncotarget.4528

1949-2553

Gui‐Qi Zhu, Sha Huang, Guiqian Huang, Liren Wang, Yi-Qian Lin, Yi-Ming Wu, Keqing Shi, Jiangtao Wang, Zhirui Zhou, Martin Braddock, Yongping Chen, Mengtao Zhou, Ming‐Hua Zheng,

Liver Disease and Transplantation

// Gui-Qi Zhu 1,2,* , Sha Huang 1,2,* , Gui-Qian Huang 1,3,* , Li-Ren Wang 1,2 , Yi-Qian Lin 1,3 , Yi-Ming Wu 1,2 , Ke-Qing Shi 1,4 , Jiang-Tao Wang 1,2 , Zhi-Rui Zhou 5 , Martin Braddock 6 , Yong-Ping Chen 1,4 , Meng-Tao Zhou 7 and Ming-Hua Zheng 1,4 1 Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 2 School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China 3 Renji School of Wenzhou Medical University, Wenzhou, China 4 Institute of Hepatology, Wenzhou Medical University, Wenzhou, China 5 Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 6 Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom 7 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China * These authors are Co-first author Correspondence to: Ming-Hua Zheng, email: // Meng-Tao Zhou, email: // Keywords : primary biliary cirrhosis, UDCA-based therapy, adverse events, network meta-analysis, indirect comparison Received : April 11, 2015 Accepted : May 22, 2015 Published : June 19, 2015 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.