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A SYSTEMATIC REVIEW OF THE EFFECTIVENESS OF PEGYLATED INTERFERON, LAMIVUDINE, ADEFOVIR AND ENTECAVIR FOR THE TREATMENT OF HEPATITIS
BG Woo, Y Nishikawa, J Heathcote, M Sherman, T Einarson, W Ungar, M Krahn
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON
BACKGROUND: Treatment options for chronic hepatitis B (CHB) are constantly evolving. A comprehensive, recent analysis comparing the effectiveness of all available treatments is not available.
Aims: To systematically review the effectiveness of pegylated interferon (PEG), lamivudine (LAM), adefovir (ADV) and entecavir (ENT) in treating CHB.
METHODS: Pubmed, Embase, Cochrane, and Econlit were searched for randomized controlled trials assessing the efficacy of the selected drugs for treating CHB. Among trials that met our inclusion critera, we abstracted data describing normalization of ALT, HBV DNA, sustained biochemical response, HBeAg seroconversion, histological improvement, drop-outs and adverse events. Intention-to-treat data were combined using a random-effects meta-analysis, with missing data considered as treatment failures. Outcomes were expressed as relative risks with 95% confidence intervals.
RESULTS: The initial search yielded 2064 references. 20 studies were included.127 were excluded for inadequate blinding, allocation concealment, randomization and reporting of outcomes. Trials involved 5573 patients (4121 males, 1309 females), ranging from 200-814 patients. Mean age was 40.7. Monotherapy comparisons available were LAM, ADV, and ENT versus placebo, and LAM versus PEG, ADV and ENT. Combination and sequential therapies were also included. Clinically relevant dosages were used for a treatment duration of one year. Eleven trials studied HBeAg-positive patients, four trials studied HBeAg-negative patients, and four trials studied both. Small numbers of trials for comparison led to pooling of eAg-positive and eAg-negative studies.
No treatment was superior for all outcome measures. Monotherapy was superior to placebo. Comparisons of single drugs favored treatment with ADV or ENT over LAM or PEG. In indirect comparisons, LAM was superior to PEG with better clinical outcomes and fewer adverse events and patient dropouts. Combination and sequential treatments were not superior, but comparisons were limited by our one-year follow-up.
CONCLUSION: Monotherapy with ADV or ENT are the most attractive treatment options within the first year of treatment. Further research on combination and sequential therapies may provide better options but presently insufficient evidence exists to support this approach.
This study was partially funded by Gilead Sciences