Kavita Patel

Treatment of chronic hepatitis C patients with persistently normal alanine aminotransferase levels with the combination of peginterferon α-2a (40 kDa) plus ribavirin: Impact on health-related quality of life

Background:  Peginterferon α‐2a (40 kDa) plus ribavirin is equally effective in chronic hepatitis C patients with normal or elevated alanine aminotransferase (ALT) values. This analysis, in patients with normal ALT levels, compared health‐related quality of life (HRQoL) measurements between untreated control patients and treated patients grouped by virological response. HRQoL in the present population was also compared with HRQoL in patients with elevated ALT levels, observed in a previous study.

Cost-effectiveness of peginterferon alfa-2a compared to lamivudine treatment in patients with hepatitis B e antigen positive chronic hepatitis B in Taiwan

Background:  Peginterferon alfa‐2a (40KD), a new treatment option for patients with chronic hepatitis B (CHB), offers improved efficacy with a defined treatment duration compared with lamivudine, but at a higher cost. We undertook an economic evaluation of peginterferon alfa‐2a from the perspective of the Taiwan Bureau of National Health Insurance to assess the clinical outcomes and costs of 48 weeks of peginterferon alfa‐2a for the treatment of patients with hepatitis B e antigen (HBeAg)‐positive CHB, compared to lamivudine treatment for 48 weeks.

Health-related quality of life with enfuvirtide (ENF; T-20) in combination with an optimized background regimen.

SummaryThis study assessed the impact of enfuvirtide on health-related quality of life (HRQoL). Patients enrolled in 2 phase 3 trials T-20 versus Optimized Regimen Only (TORO 1 and 2) completed the Medical Outcomes Study (MOS)-HIV questionnaire at baseline and at 4, 8, 16, and 24 weeks. A total of 995 treatment-experienced HIV-1–infected individuals received either self-administered enfuvirtide (90 mg twice daily) + optimized background (OB) or OB alone and had at least 1 follow-up visit. Data from the 2 clinical trials were pooled. Analysis of covariance was used to evaluate changes in the 10 MOS-HIV scale scores and 2 summary scores. Least-squares means for these changes were calculated and used to test for between-group differences. There were no significant between-group differences in any HRQoL measure at baseline. Most MOS-HIV scores showed improvement in the enfuvirtide arm compared with OB alone, although only some of these were significant. Improvements in the general health scale were significantly higher in the enfuvirtide arm compared with OB alone at all post-baseline time points. No scale or summary score for the OB arm showed a significantly greater improvement in score from baseline compared with the enfuvirtide arm, at any time point. The mental health summary score at 24 weeks was significantly higher in the enfuvirtide arm compared with OB alone. Enfuvirtide in addition to an OB regimen does not adversely affect and may improve HRQoL when self-administered for up to 24 weeks by treatment-experienced, HIV-1–infected individuals.

HBeAg-Negative Chronic Hepatitis B: Cost-Effectiveness of Peginterferon Alfa-2a Compared to Lamivudine in Taiwan

OBJECTIVE In Taiwan, the carrier rate of hepatitis B surface antigen is 15% to 20%, one of the highest in the world. Among chronic hepatitis B (CHB) patients, hepatitis B e antigen (HBeAg)-negative accounts for approximately 40% to 50% of these patients. A recent study found that peginterferon alfa-2a (40 KD) is more effective than lamivudine in treating HBeAg-negative CHB, but its cost-effectiveness has not been evaluated. Our objective is to evaluate the incremental cost-effectiveness of 48 weeks of peginterferon alfa-2a compared to 48 weeks of lamivudine, from the perspective of the Taiwan Bureau of National Health Insurance. METHODS A Markov model was used to simulate the natural history of HBeAg-negative CHB in a cohort of 40-year-old patients. Efficacy, disease progression, economic, and quality-of-life data were derived from published literature and a survey of clinical experts in Taiwan. Life expectancy, quality-adjusted life expectancy, lifetime costs in New Taiwan Dollars (NTD) (1 USD = 31.96 NTD), and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS The gain in quality-adjusted life-years (QALYs) for 48 weeks of peginterferon alfa-2a compared to 48 weeks of lamivudine was 0.45 at an additional cost of 157,000 NTD (4900 USD), resulting in an ICER of 347,000 NTD (10,900 USD) per QALY gained. The 95% central range for the ICER from a probabilistic sensitivity analysis was 228,000-566,000 NTD (7100-17,700 USD). CONCLUSIONS In HBeAg-negative CHB, 48 weeks of treatment with peginterferon alfa-2a compared to 48 weeks of lamivudine appears to offer life expectancy and quality-of-life improvements at an acceptable cost-effectiveness ratio.

Cost-effectiveness of peginterferon α-2a compared with lamivudine treatment in patients with HBe-antigen-positive chronic hepatitis B in the United Kingdom

Background Peginterferon &agr;-2a (40 kDa), a new treatment for chronic hepatitis B, produces seroconversion within 48 weeks in approximately 32% of HBeAg-positive patients. Over a defined treatment duration it offers improved efficacy over lamivudine, but at higher cost. We assessed the clinical outcomes and costs, from the perspective of the UK National Health Service, of 48 weeks of peginterferon &agr;-2a (40 kDa) vs. 4 years of lamivudine. Methods Cost-effectiveness was analysed using a state-transition Markov model simulating HBeAg-positive chronic hepatitis B natural history. Efficacy data were obtained from a large randomized trial comparing peginterferon &agr;-2a (40 kDa) with lamivudine over 48 weeks. Use of adefovir salvage treatment for lamivudine-resistant patients was also evaluated. Long-term lamivudine efficacy, treatment durability, disease progression, cost, and quality-of-life estimates were derived from the literature. One-way and probabilistic sensitivity analyses evaluated uncertainty. Results Treatment with peginterferon &agr;-2a (40 kDa) for 48 weeks resulted in higher discounted total healthcare costs (£3100), but an increase of 0.3 discounted quality-adjusted life years compared with long-term lamivudine, giving an incremental cost-effectiveness ratio of £10 400 per quality-adjusted life year gained (£8300–£15 400 in one-way sensitivity analyses). The cost-effectiveness acceptability curve showed intervention was below the £30 000/QALY threshold in over 95% of the simulations. When adefovir was included for patients with lamivudine resistance, peginterferon &agr;-2a (40 kDa) had an incremental cost of £6100/QALY gained. Conclusions Treatment with peginterferon &agr;-2a (40 kDa) for a defined duration of 48 weeks, although more expensive than lamivudine therapy, provides improvement in health outcomes, with a cost-effectiveness ratio well below the current UK cost-effectiveness threshold.

The economics of treating chronic hepatitis C patients with peginterferon alpha-2a (40 kDa) plus ribavirin presenting with persistently normal aminotransferase.

Summary.  Peginterferon α‐2a (40 kDa) plus ribavirin is effective at achieving sustained viral response compared with no treatment in patients with chronic hepatitis C (CHC) and persistently normal aminotransferase levels (PNALT). The cost‐effectiveness of treating CHC in the setting of PNALT has not been assessed. Disease progression in patients with PNALT was simulated in a Markov model. The rate of fibrosis progression, quality of life and costs for each health state were based on literature estimates. The perspective of the Italian National Health Service was adopted and costs (€2003) and benefits were discounted at 3%. Sensitivity analyses were performed on important parameters. The primary analysis compared combination therapy with peginterferon α‐2a (40 kDa) plus ribavirin to no treatment in a cohort of patients with mean age 45 years, and was based on findings from a multinational, randomized trial in patients with PNALT. In genotype 1 patients, the risk of cirrhosis at 30 years is forecast to fall from 32% with no treatment to 19% with combination therapy, increasing quality‐adjusted life years (QALYs) by 0.74 years at an incremental cost per QALY gained of €16 831. The 30‐year risk of cirrhosis in genotype 2 or 3 is projected to fall to 9% with combination therapy, an increase in QALYs of 1.34 years, at an incremental cost per QALY gained of €3000. Thus treatment of PNALT with peginterferon α‐2a (40 kDa) plus ribavirin is projected to reduce the incidence of cirrhosis, increase life expectancy and have an acceptable cost‐effectiveness ratio from a societal perspective.

PGI5 COST-EFFECTIVENESS OF TREATING ADULTS WITH CHRONIC HEPATITIS C (CHC) AND PERSISTENTLY NORMAL ALANINE AMINOTRANSFERASE (PNALT) WITH PEGINTERFERON ALFA-2A (40KD) (PEGASYS) PLUS RIBAVIRIN (COPEGUS)

cation was developed as an alternative to the complete wrap in order to reduce the prevalence of post-operative symptoms such as bloating and dysphagia. OBJECTIVE: To systematically review the effectiveness of two different surgical techniques of laparoscopic fundoplication (partial versus total) for the treatment of GORD in adults. METHODS: A systematic search of the literature was carried out. All randomised trials comparing total versus partial laparoscopic fundoplication were included. The main outcome measure was the number of patients who were symptom free at follow-up. Other outcome measures reviewed included clinical outcomes, PROs and QoL. In addition any long-term follow-up data were reviewed. RESULTS: Seven randomised trials identified met the inclusion criteria for this review. All trials included compared laparoscopic total fundoplication compared to partial fundoplication. Post-trial follow-up results varied between 3–6 months and a variety of outcome measures were reported. One study reported 12-month results. There was no reporting on quality of life, though three trials reported PROs. Dysphagia was more frequently reported in patients undergoing total fundoplication compared to partial warp RR 2.82 [95% CI: 18.4, 4.32]. No significant differences in post-operative bloating was found between the two surgical techniques. There was no significant difference in the number of patients reporting either “good” or “excellent” outcomes between techniques RR 0.97 [95% CI: 0.89, 1.05]. CONCLUSIONS: Evidence from trials supports the view that both total and partial fundoplication are clinically effective for treating GORD. However, long-term efficacy and QoL data are needed to choose one technique over the other.

Cost Effectiveness of Peginterferon alpha-2a Plus Ribavirin versus Interferon alpha-2b Plus Ribavirin as Initial Therapy for Treatment-Naive Chronic Hepatitis C. The Authors' Reply

although it should be borne in mind that growth Cost Effectiveness of factors were not allowed in the clinical studies. On the other hand, adverse events more frequent with Peginterferon α-2a Plus conventional interferon-α therapy include flu-like symptoms and depression. We elected to incorpoRibavirin versus rate adverse events in the model through their imInterferon α-2b Plus pact on treatment discontinuation, rather than microcosting the events using assumptions about treatRibavirin as Initial ment patterns related to adverse events.