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

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Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B : an updated systematic review and economic evaluation. / Shepherd, J; Jones, Jeremy; Baxter, L; Gospodarevskaya, E; Hartwell, D; Harris, P; Price, A.

In: Health Technology Assessment, Vol. 13, No. 35, 07.2009, p. 1-172, iii.

Research output: Contribution to journalReview articlepeer-review

Harvard

Shepherd, J, Jones, J, Baxter, L, Gospodarevskaya, E, Hartwell, D, Harris, P & Price, A 2009, 'Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation', Health Technology Assessment, vol. 13, no. 35, pp. 1-172, iii. https://doi.org/10.3310/hta13350

APA

Shepherd, J., Jones, J., Baxter, L., Gospodarevskaya, E., Hartwell, D., Harris, P., & Price, A. (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), 1-172, iii. https://doi.org/10.3310/hta13350

Vancouver

Shepherd J, Jones J, Baxter L, Gospodarevskaya E, Hartwell D, Harris P et al. Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation. Health Technology Assessment. 2009 Jul;13(35):1-172, iii. https://doi.org/10.3310/hta13350

Author

Shepherd, J ; Jones, Jeremy ; Baxter, L ; Gospodarevskaya, E ; Hartwell, D ; Harris, P ; Price, A. / Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B : an updated systematic review and economic evaluation. In: Health Technology Assessment. 2009 ; Vol. 13, No. 35. pp. 1-172, iii.

Bibtex

@article{95c8b223fdcb4d62be5475c90d3f440c,
title = "Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation",
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-alpha) 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-alpha-2a and PEG-alpha-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-alpha) 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-alpha-2b and one (from the original literature search) compared PEG-alpha-2b plus LAM with PEG-alpha-2b monotherapy. No RCTs of PEG-alpha-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-alpha trials, there were statistically significant differences favouring PEG-alpha-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-alpha-2b and IFN-alpha and the comparison between different staggered regimens of the commencement of PEG-alpha-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-alpha-2a; the remainder assessed ADV. PEG-alpha-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-alpha-2a was 10,444 pounds 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-alpha-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of 20,000 pounds per QALY, and 86% at a willingness-to-pay threshold of 30,000 pounds per QALY.CONCLUSIONS: Both ADV and PEG-alpha 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.",
keywords = "Adenine/administration & dosage, Adult, Aged, Antiviral Agents/administration & dosage, Female, Hepatitis B, Chronic/drug therapy, Humans, Interferon-alpha/administration & dosage, Male, Middle Aged, Organophosphonates/administration & dosage",
author = "J Shepherd and Jeremy Jones and L Baxter and E Gospodarevskaya and D Hartwell and P Harris and A Price",
year = "2009",
month = jul,
doi = "10.3310/hta13350",
language = "English",
volume = "13",
pages = "1--172, iii",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "NIHR Journals Library",
number = "35",

}

RIS

TY - JOUR

T1 - Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B

T2 - an updated systematic review and economic evaluation

AU - Shepherd, J

AU - Jones, Jeremy

AU - Baxter, L

AU - Gospodarevskaya, E

AU - Hartwell, D

AU - Harris, P

AU - Price, A

PY - 2009/7

Y1 - 2009/7

N2 - OBJECTIVE: To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-alpha) 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-alpha-2a and PEG-alpha-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-alpha) 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-alpha-2b and one (from the original literature search) compared PEG-alpha-2b plus LAM with PEG-alpha-2b monotherapy. No RCTs of PEG-alpha-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-alpha trials, there were statistically significant differences favouring PEG-alpha-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-alpha-2b and IFN-alpha and the comparison between different staggered regimens of the commencement of PEG-alpha-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-alpha-2a; the remainder assessed ADV. PEG-alpha-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-alpha-2a was 10,444 pounds 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-alpha-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of 20,000 pounds per QALY, and 86% at a willingness-to-pay threshold of 30,000 pounds per QALY.CONCLUSIONS: Both ADV and PEG-alpha 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.

AB - OBJECTIVE: To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-alpha) 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-alpha-2a and PEG-alpha-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-alpha) 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-alpha-2b and one (from the original literature search) compared PEG-alpha-2b plus LAM with PEG-alpha-2b monotherapy. No RCTs of PEG-alpha-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-alpha trials, there were statistically significant differences favouring PEG-alpha-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-alpha-2b and IFN-alpha and the comparison between different staggered regimens of the commencement of PEG-alpha-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-alpha-2a; the remainder assessed ADV. PEG-alpha-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-alpha-2a was 10,444 pounds 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-alpha-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of 20,000 pounds per QALY, and 86% at a willingness-to-pay threshold of 30,000 pounds per QALY.CONCLUSIONS: Both ADV and PEG-alpha 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.

KW - Adenine/administration & dosage

KW - Adult

KW - Aged

KW - Antiviral Agents/administration & dosage

KW - Female

KW - Hepatitis B, Chronic/drug therapy

KW - Humans

KW - Interferon-alpha/administration & dosage

KW - Male

KW - Middle Aged

KW - Organophosphonates/administration & dosage

U2 - 10.3310/hta13350

DO - 10.3310/hta13350

M3 - Review article

C2 - 19607759

VL - 13

SP - 1-172, iii

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 35

ER -

ID: 10214314