Authors' objectives:

The aim of this review was to assess the clinical effectiveness and cost-effectiveness of adefovirdipivoxil (ADV) and pegylated interferon alfa-2a (PEG) for the treatment of adults with chronic hepatitis B infection (CHB).

Authors' results and conclusions: A total of 1086 references to clinical effectiveness studies were identified, of which seven fully published RCTs and one systematic review met the inclusion criteria. Four of the RCTs evaluated the effectiveness of ADV and three reported results for PEG. In addition, a conference abstract was included reporting interim results from an on-going Phase II RCT of ADV in combination with LAM. The published trials were of good quality, although details of randomisation and allocation of concealment were poorly reported. ADV was significantly more effective than placebo. Response rates were in the range 21-51% compared with 0%, respectively. For patients resistant to LAM, response rates were significantly higher for those treated with ADV in addition to on-going LAM (35-85%) than those who continued on LAM with placebo (0-11%). Significant alanineaminotransferase (ALT) reductions to normal levels were observed in all studies. For treatment-naive patients, seroconversion rates were 12-14% for ADV compared with 6% for placebo (statistically significant), rates were higher for LAM-resistant patients who received ADV in addition to on-going LAM (8%) than those who continued on LAM with placebo (2%) (no significance value was reported), and rates were higher for LAM-resistant patients who switched to ADV than those who continued on LAM with placebo (11 versus 0%, respectively; not statistically significant). HBsAg loss or seroconversion was observed in less than 5% of patients taking ADV. Two ADV studies reported changes in liver histology. In general, histological improvement and necroinflammatory activity/fibrosis scores were significantly better in ADV groups than in placebo groups. Dose discontinuations for safety reasons were low for patients receiving ADV. With the exception of headache, the most commonly reported adverse events were often seen in the placebo groups in similar proportions to the ADV groups, with different trials reporting conflicting results. PEG/LAM dual therapy and PEG monotherapy were similar in effect on HBV DNA and ALT levels, and both were significantly superior to LAM monotherapy. Response rates were higher for HBeAg-negative patients than for HBeAg-positive patients. HBeAg seroconversion rates at follow-up were significantly higher for PEG monotherapy patients than for those receiving either a combination of PEG and LAM or LAM monotherapy (32, 27 and 19%, respectively). For the comparison between PEG and IFN-2a, there was a significant difference in the combined outcome of ALT normalisation, HBV DNA response and HBeAgseroconversion at follow-up (24 versus 12%, respectively). Changes in liver histology were reported by two studies. There was no statistically significant difference in histological improvement between the PEG monotherapy groups, the LAM monotherapy groups and the dual therapy groups. Two PEG trials reported small percentages (up to 5%) of HBsAg loss or seroconversion among patients receiving PEG either as monotherapy or in combination with LAM, but no HBsAg loss or seroconversion was reported in those receiving LAM monotherapy. Health-related quality of life (HRQoL) scores, as measured by the Short Form with 36 Items, decreased during treatment, but returned to at least baseline levels at follow-up (based on unpublished data). For HBeAg-positive patients, there were no significant differences in scores between treatment groups. Dose discontinuations for safety reasons were significantly higher for patients receiving PEG than for patients receiving LAM monotherapy. The most commonly reported adverse events in the PEG studies were headache, pyrexia, fatigue, myalgia and alopecia.

Authors' recommendations: ADV and PEG are associated with significant improvements in a number of biochemical, virological and histological outcomes in both HBeAg-positive and -negative patients. For a small proportion of patients this is associated with resolution of infection. For another proportion it leads to remission and a reduced risk of progressing to cirrhosis, hepatocellular carcinoma, liver transplant and death. For others who do not respond or who relapse, retreatment with another agent is necessary. The results of our cost-effectiveness analysis demonstrate that incremental costs per QALY for a range of comparisons were between 5994 GBP and 16,569 GBP and within the range considered by NHS decision-makers to represent good value for money. When subjected to sensitivity analysis, most costs per QALY estimates remained under 30,000 GBP. Further RCT evidence of the effectiveness of anti-viral treatment is required, particularly for subgroups of patients with different genotypes, patients with cirrhosis, patients from different ethnic groups, patients with co-infections (e.g. HIV, HCV) and co-morbidities, liver transplant patients and children and adolescents.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.hta.ac.uk/1463

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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