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Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation

Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation
Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation
Objective:
To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-?) for the treatment of chronic hepatitis B (CHB).

Data sources:
Thirteen bibliographic databases were searched including MEDLINE, EMBASE and the Cochrane Library. Searches were run from the beginning of 2005 to September 2007.

Review methods:
For the clinical effectiveness review, randomised controlled trials (RCTs) comparing ADV, PEG-?-2a and PEG-?-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-?) and lamivudine (LAM), were included. Outcomes included biochemical, histological and virological response to treatment, drug resistance and adverse effects. A systematic review of economic evaluations of antiviral treatments for CHB was conducted. The economic Markov model used in the 2006 report was updated in terms of utility values, discount rates and costs.

Results:
Of the 82 papers retrieved for detailed screening, eight RCTs were included. Three evaluated ADV, four evaluated PEG-?-2b and one (from the original literature search) compared PEG-?-2b plus LAM with PEG-?-2b monotherapy. No RCTs of PEG-?-2a were identified. One ADV trial showed a statistically significant difference between ADV and placebo in terms of ALT response and HBV DNA levels, favouring ADV. Following withdrawal of ADV, levels were similar to those in placebo patients. In the ADV versus ADV plus LAM trial, there was a statistically significant difference in favour of the combination treatment. In the PEG-? trials, there were statistically significant differences favouring PEG-?-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-?-2b and IFN-? and the comparison between different staggered regimens of the commencement of PEG-?-2b and LAM, there were no statistically significant differences between groups. Four full economic evaluations were identified, in addition to one identified in the original report. Two assessed PEG-?-2a; the remainder assessed ADV. PEG-?-2a was associated with increased treatment costs and gains in quality-adjusted life expectancy. In a UK study, the incremental cost-effectiveness ratio (ICER) for PEG-?-2a was £10,444 per QALY gained compared with LAM. Evaluations of ADV found that LAM monotherapy was dominated; the ICER for ADV monotherapy compared with 'doing nothing' was $19,731. The results of the updated analysis were generally robust to changes in deterministic sensitivity analysis. In a probabilistic sensitivity analysis, the same sequence of treatments was identified as optimal. In a probabilistic sensitivity analysis, PEG-?-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of £20,000 per QALY, and 86% at a willingness-to-pay threshold of £30,000 per QALY.

Conclusions:
Both ADV and PEG-? are beneficial for patients with CHB in terms of suppressing viral load, reducing liver damage-associated biochemical activity, inducing HBeAg seroconversion, and reducing liver fibrosis and necroinflammation. The effects of long-term treatment with ADV are generally durable, with relatively low rates of resistance. In most cases, cost-effectiveness estimates were within acceptable ranges. Further research should assess the clinical effectiveness and cost-effectiveness of newer antiviral agents in relation to existing drugs, including the role of initiating treatment with combination therapy.
systematic review, economic evaluation, hepatisis B
1366-5278
1-196
Jones, Jeremy
270b303b-6bad-4be7-8ea0-63d0e8015c91
Shepherd, Jonathan
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Baxter, Louise
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Gospodarevskaya, Elena
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Hartwell, Debbie
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Harris, Petra
0e15de29-ece4-43e6-9861-4e20bcee5acd
Jones, Jeremy
270b303b-6bad-4be7-8ea0-63d0e8015c91
Shepherd, Jonathan
dfbca97a-9307-4eee-bdf7-e27bcb02bc67
Baxter, Louise
c2e955db-6d0e-43c1-8a16-98981727d98e
Gospodarevskaya, Elena
38d92bb3-d2e6-4400-a3f8-513c780fadb2
Hartwell, Debbie
e6a0eaa0-956d-45fb-9b7d-03ca1af3334c
Harris, Petra
0e15de29-ece4-43e6-9861-4e20bcee5acd

Jones, Jeremy, Shepherd, Jonathan, Baxter, Louise, Gospodarevskaya, Elena, Hartwell, Debbie and Harris, Petra (2009) Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation. Health Technology Assessment, 13 (35), 1-196. (doi:10.3310/hta13350). (PMID:19607759)

Record type: Article

Abstract

Objective:
To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-?) for the treatment of chronic hepatitis B (CHB).

Data sources:
Thirteen bibliographic databases were searched including MEDLINE, EMBASE and the Cochrane Library. Searches were run from the beginning of 2005 to September 2007.

Review methods:
For the clinical effectiveness review, randomised controlled trials (RCTs) comparing ADV, PEG-?-2a and PEG-?-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-?) and lamivudine (LAM), were included. Outcomes included biochemical, histological and virological response to treatment, drug resistance and adverse effects. A systematic review of economic evaluations of antiviral treatments for CHB was conducted. The economic Markov model used in the 2006 report was updated in terms of utility values, discount rates and costs.

Results:
Of the 82 papers retrieved for detailed screening, eight RCTs were included. Three evaluated ADV, four evaluated PEG-?-2b and one (from the original literature search) compared PEG-?-2b plus LAM with PEG-?-2b monotherapy. No RCTs of PEG-?-2a were identified. One ADV trial showed a statistically significant difference between ADV and placebo in terms of ALT response and HBV DNA levels, favouring ADV. Following withdrawal of ADV, levels were similar to those in placebo patients. In the ADV versus ADV plus LAM trial, there was a statistically significant difference in favour of the combination treatment. In the PEG-? trials, there were statistically significant differences favouring PEG-?-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-?-2b and IFN-? and the comparison between different staggered regimens of the commencement of PEG-?-2b and LAM, there were no statistically significant differences between groups. Four full economic evaluations were identified, in addition to one identified in the original report. Two assessed PEG-?-2a; the remainder assessed ADV. PEG-?-2a was associated with increased treatment costs and gains in quality-adjusted life expectancy. In a UK study, the incremental cost-effectiveness ratio (ICER) for PEG-?-2a was £10,444 per QALY gained compared with LAM. Evaluations of ADV found that LAM monotherapy was dominated; the ICER for ADV monotherapy compared with 'doing nothing' was $19,731. The results of the updated analysis were generally robust to changes in deterministic sensitivity analysis. In a probabilistic sensitivity analysis, the same sequence of treatments was identified as optimal. In a probabilistic sensitivity analysis, PEG-?-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of £20,000 per QALY, and 86% at a willingness-to-pay threshold of £30,000 per QALY.

Conclusions:
Both ADV and PEG-? are beneficial for patients with CHB in terms of suppressing viral load, reducing liver damage-associated biochemical activity, inducing HBeAg seroconversion, and reducing liver fibrosis and necroinflammation. The effects of long-term treatment with ADV are generally durable, with relatively low rates of resistance. In most cases, cost-effectiveness estimates were within acceptable ranges. Further research should assess the clinical effectiveness and cost-effectiveness of newer antiviral agents in relation to existing drugs, including the role of initiating treatment with combination therapy.

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Published date: 2009
Keywords: systematic review, economic evaluation, hepatisis B

Identifiers

Local EPrints ID: 143837
URI: http://eprints.soton.ac.uk/id/eprint/143837
ISSN: 1366-5278
PURE UUID: 7362e110-5c46-4d34-bb16-6836328b4e3b
ORCID for Jonathan Shepherd: ORCID iD orcid.org/0000-0003-1682-4330

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Date deposited: 13 Apr 2010 11:55
Last modified: 14 Mar 2024 02:38

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Contributors

Author: Jeremy Jones
Author: Louise Baxter
Author: Elena Gospodarevskaya
Author: Debbie Hartwell
Author: Petra Harris

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