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PICO 6: Treatment Pegylated Interferon Plus Ribavirin Versus

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PICO 6: Treatment Pegylated Interferon Plus Ribavirin Versus WHO/HIV/2014.32 © World Health Organization 2014 Global Hepatitis Programme Guideline development for Hepatitis C virus Screening, Care and Treatment in low- and middle-income countries PICO 6: Treatment Pegylated interferon plus ribavirin versus standard interferon plus ribavirin for chronic hepatitis C infection: a meta-analytical systematic review Conducted by the Burnet Institute, Melbourne and Health Protection Scotland, Glasgow 23 June 2013 Review Members Dr Brendan Quinn Burnet Institute, Melbourne Dr Jess Howell Royal Melbourne Hospital, Melbourne Dr SweeLin Mei St Vincent’s Hospital, University of Melbourne Dr Joseph Doyle Burnet Institute, Melbourne Dr Esther Aspinall Health Protection Scotland, Glasgow Prof Sharon Hutchinson Caledonian University, Glasgow Prof Margaret Hellard Burnet Institute, Melbourne Review Advisory Group Dr Mark Stoove Burnet Institute, Melbourne Prof David Goldberg Health Protection Scotland Prof Stanley Luchters Burnet Institute, Melbourne Dr Alexander Thompson St Vincent’s Hospital, University of Melbourne Dr Stefan Wiktor WHO Global Hepatitis Program Mr Tim Nguyen WHO Global Hepatitis Program Dr Bryce Smith Centre for Disease Control and Prevention, Atlanta Dr Yngve Falck-Ytter Case Western Reserve University, Ms Rebecca Morgan Centre for Disease Control and Prevention, Atlanta © World Health Organization 2014 All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; E-mail: [email protected]). Requests for permission to reproduce or translate WHO publications –whether for sale or for non- commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. P a g e | 2 PICO 6 (Treatment): PEG/RBV versus IFN/RBV for chronic HCV Table of Contents BACKGROUND ..................................................................................................................................... 4 METHODS ............................................................................................................................................ 4 RESULTS .............................................................................................................................................. 8 CONCLUSION ..................................................................................................................................... 10 FIGURES AND TABLES ........................................................................................................................ 11 Figure 1: Systematic Review Flowchart ........................................................................................ 11 Table 1: Summaries of included studies ....................................................................................... 12 Figure 2: Failure to achieve SVR among patients with chronic HCV administered PEG versus standard IFN (both plus RBV) ........................................................................................................ 37 Figure 3: Sub-group analysis: Failure to achieve SVR among HCV genotype 1 patients administered PEG versus standard IFN (both plus RBV) ............................................................... 38 Figure 4: Sub-group analysis: Failure to achieve SVR among non-genotype 1 HCV patients administered PEG versus standard IFN (both plus RBV) ............................................................... 39 Figure 5: Sub-group analysis: Failure to achieve SVR among cirrhotic patients administered PEG versus standard IFN (both plus RBV)............................................................................................. 40 Figure 6: Sub-group analysis: Failure to achieve SVR among non-cirrhotic patients administered PEG versus standard IFN (both plus RBV) ..................................................................................... 41 Figure 7: Treatment discontinuation due to adverse events among chronic HCV administered PEG versus standard IFN (both plus RBV) ..................................................................................... 42 Figure 8: All-cause mortality among patients with chronic HCV administered PEG versus standard IFN (both plus RBV) ........................................................................................................ 43 Figure 9: Liver-related mortality among patients with chronic HCV administered PEG versus standard IFN (both plus RBV) ........................................................................................................ 44 Figure 10: Hepatic decompensation among patients with chronic HCV administered PEG versus standard IFN (both plus RBV) ........................................................................................................ 45 Table 2: GRADE summary of findings ........................................................................................... 46 Table 3: Indirect evidence from systematic reviews of HCV treatment in Children and PWID .... 48 APPENDICIES ..................................................................................................................................... 49 Appendix 1: Search syntax ............................................................................................................ 49 Appendix 2: Cochrane Collaboration’s tool for assessing risk of bias........................................... 50 Appendix 3: GRADE approach to assessing the quality of evidence across studies ..................... 51 REFERENCES ...................................................................................................................................... 52 P a g e | 3 PICO 6 (Treatment): PEG/RBV versus IFN/RBV for chronic HCV BACKGROUND The World Health Organization (WHO) estimates that between 130 and 150 million people are chronically infected with hepatitis C virus (HCV) worldwide [1]. People with untreated HCV are at increased risk of liver cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality [2]. According to the most recent guidelines of the European Association for the Study of the Liver (EASL) [3], the combination of pegylated interferon and ribavirin therapy is the approved standard of care for treating individuals with chronic HCV. This review assessed the available evidence to determine whether pegylated interferon is more effective at treating chronic HCV compared to standard interferon with respect to maximising the chance of achieving a sustained virological response (SVR), and reducing morbidity (i.e., decompensated liver disease/hepatocellular carcinoma), mortality and other serious adverse events. METHODS Narrative review question: Among people with chronic HCV and receiving antiviral treatment, is treatment with pegylated interferon and ribavirin therapy more effective than treatment with standard interferon and ribavirin therapy? PICO question: Population: Treatment-naïve adults and children with chronic HCV infection Intervention: Treatment with pegylated interferon and ribavirin therapy Comparison: Treatment with standard interferon and ribavirin therapy Outcomes: Rates of SVR, decompensated liver disease, hepatocellular carcinoma, all-cause mortality and treatment-related adverse events leading to discontinuation of therapy; quality of life. Cost outcomes will require economic modelling which will be conducted separately from this protocol. Study type/limits: Experimental studies (human) published between 1994 and the present Search strategy A systematic review was conducted using the following electronic databases and information sources: P a g e | 4 PICO 6 (Treatment): PEG/RBV versus IFN/RBV for chronic HCV - OVID MEDLINE, OVID EMBASE, LILACS, and the Cochrane Library (CENTRAL and DARE) (without language restrictions); - Unpublished/ongoing research presented at relevant international conferences; - Conference proceedings and clinical trials registries from EASL, AASLD, APASL, and ClinicalTrials.gov; - Reference lists of all relevant articles and reviews; - Recommendations from Guideline Development Group (GDG) members and other experts in the field; - Relevant articles identified during the conduct
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