4K-2 CURRENT TREATMENT FOR CHRONIC HEPATITIS B (CHB): A SYSTEMATIC REVIEW AND A NETWORK META-ANALYSIS

Tuesday, October 20, 2015: 1:45 PM
Grand Ballroom B (Hyatt Regency St. Louis at the Arch)

William W. L. Wong, Ph.D.1, Petros Pechlivanoglou, MSc, PhD1, Aysegul Erman2, Yasmin Saeed, BScPhm2, Mina Tadrous, PhD3, Mona Younis2, Noha Zaki Rayad, PhD4, Joanna M. Bielecki, BSC, MISt1, Valeria E. Rac, MD, PhD1 and Murray D Krahn, MD, MSc, FRCPC1, (1)Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto, Toronto, ON, Canada, (2)Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada, (3)The Ontario Drug Policy Research Network, St. Michael's Hospital, Toronto, ON, Canada, (4)Toronto, ON, Canada
Purpose: An estimated 240 million people worldwide are chronically infected with the hepatitis B virus. Of those infected with CHB, 40% will silently progress to liver cirrhosis and are at risk of dying prematurely of liver failure or liver cancer.  The objective of this review is to identify and synthesize the available Randomized Controlled Trials (RCTs) evidence investigating the comparative effectiveness and safety between the available CHB treatments (standard interferon, pegylated-interferon, adefovir, lamivudine, entecavir, telbivudine, and tenofovir) in treatment-naive individuals.

Method: Databases (PubMed, Embase, Cochrane Library and Web of Science) were searched for RCTs investigating the therapy in hepatitis B e antigen (HBeAg) positive and/or HBeAg negative patients with CHB published in English before October 29, 2014.  Network meta-analyses (NMA) were conducted to estimate pooled effectiveness and safety data using the following outcomes:  1) Efficacy for HBeAg positive patients: virologic response; alanine aminotransferase (ALT) normalization; HBeAg loss; HBeAg seroconversion; and HBsAg loss; 2) Efficacy for HBeAg negative patients: virologic response and ALT normalization; and 3) Safety: Serious adverse events, any adverse events, and withdrawal due to adverse events.

Result: A total of 62 studies were selected for inclusion. In HBeAg positive patients, tenofovir was most effective in achieving virologic response (predicted probability: 86%); tenofovir was found significantly better than adefovir, telbivudine, entecavir, pegylated interferon and interferon.  In terms of other efficacy outcomes (i.e. ALT normalization; HBeAg seroconversion; and HBsAg loss), tenofovir was not significantly better than the other treatments.  In HBeAg negative patients, tenofovir was the most effective in achieving virologic response (98%); tenofovir was significantly better than adefovir, telbivudine, pegylated interferon and interferon.  Tenofovir was not significantly better than the other treatments for ALT normalization.  There was no significant difference between tenofovir and other oral agents for safety outcomes.

Conclusion: Our study found that for HBeAg positive patients, tenofovir is the most effective treatment followed by entecavir, for the outcomes of virologic response and ALT normalization; for HBeAg loss and HBeAg seroconversion, pegylated interferon is the most effective treatment followed by tenofovir. For HBeAg negative patients, tenofovir is also the most effective treatment, followed by adefovir and entecavir, in terms of virologic response and ALT normalization. Current practice guidelines should be informed by cost-effectiveness and patient perspectives, in addition to evidence regarding effectiveness and safety.

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