Incidence: From —, Hep A declined in all age groups except group 0—19 years y ; in , group 20—29 y had the highest incidence 0. In , acute Hep B was highest 2. In , Hep C occurred in From —, Hep C increased 3. In , group 20—29 y had the highest Hep C rate 2. Hep A, B, and C declined from — in both sexes. In , Hep A dropped to 0. Hep C, 1. For Hep B, In , of Hep C—infected persons with risky behaviors, Death Rates: The death rate from Hep A was significantly lower in 0. The Hep C—related mortality rate in males was 2.
Comparative Effectiveness of Treatment for Hepatitis C in Adults | Effective Health Care Program
Absolute differences ranged up to 10 percentage points in either direction. Lower-dose pegylated interferon alfa-2b as part of dual therapy was associated with a lower likelihood of SVR than was a higher dose typically 1. Excluding the poor-quality trials 38, 47 or 1 trial that evaluated an atypical dosing regimen 46 had little effect on the pooled estimate. Two fair-quality trials found no clear difference between induction regimens of pegylated interferon alfa-2b higher initial doses followed by lower doses plus ribavirin versus standard fixed-dose dual therapy 53, Methodological shortcomings included open-label design 55 or high attrition A week boceprevir regimen 4 weeks of dual-therapy lead-in followed by 44 weeks of triple therapy was associated with a higher likelihood of SVR than was 48 weeks of dual therapy pooled RR, 1.
Other triple-therapy regimens evaluated in the trials 28 weeks with or without dual-therapy lead-in, 48 weeks without dual-therapy lead-in, or response-guided triple therapy for 28 or 48 weeks were associated with lower or similar SVR rates compared with the week regimen with lead-in. Six randomized trials compared triple therapy with telaprevir, pegylated interferon, and ribavirin versus dual therapy for genotype 1 infection Appendix Table 3 20, 31, 56— One trial used pegylated interferon alfa-2b 57 , 1 evaluated regimens with pegylated interferon alfa-2a or alfa-2b 31 , and the remainder used pegylated interferon alfa-2a.
One trial 58 was rated as good-quality and the remainder as fair-quality.
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Methodological shortcomings included open-label design or unclear blinding procedures 31, 56, 59 , unclear randomization methods 56, 58 , and unclear attrition 57, In all triple-therapy regimens, telaprevir was administered with pegylated interferon plus ribavirin for the first 8 to 12 weeks. For regimens longer than 12 weeks, dual therapy was continued to the end of treatment. Excluding a trial that evaluated pegylated interferon alfa-2b instead of alfa-2a had no effect on the estimate Two trials found no difference between 12 weeks of triple therapy and 48 weeks of dual therapy 56, 58 , and 1 trial found no difference between 48 and 24 weeks of telaprevir triple therapy Figure 3.
In patients with genotype 1 infection, 1 trial of dual therapy with pegylated interferon alfa-2b versus alfa-2a 21 , 2 trials of 48 weeks of triple therapy with boceprevir and dual-therapy lead-in versus 48 weeks of dual therapy 22, 55 , and 2 trials of triple therapy with telaprevir response-guided or fixed duration versus 48 weeks of dual therapy 20, 57 found no clear differences in RR estimates based on race, sex, age, baseline fibrosis, and weight. Across regimens, absolute SVR rates were lower in older patients, black patients, patients with more advanced fibrosis, and patients with higher viral load.
Six head-to-head trials of dual therapy with pegylated interferon alfa-2b versus alfa-2a found no difference in risk for withdrawal due to adverse events 6 trials; pooled RR, 1. Excluding 1 outlier trial RR, 4. Two trials found dual therapy with pegylated interferon alfa-2b to be associated with lower risk for serious adverse events than was dual therapy with pegylated interferon alfa-2a pooled RR, 0. There were no differences between dual-therapy regimens in risk for anemia, thrombocytopenia, depression, fatigue, myalgia, or influenza-like symptoms Appendix Table 4.
Dual therapy with pegylated interferon alfa-2b was associated with higher risk for headache 3 trials; pooled RR, 1. Excluding the low-dose pegylated interferon alfa-2b group from the IDEAL trial had little effect on pooled estimates, except that pegylated interferon alfa-2b became associated with increased risk for depression 3 trials; pooled RR, 1.
Excluding 2 poor-quality trials had little effect on pooled estimates 24, Two trials found a week boceprevir regimen with dual-therapy lead-in was associated with higher risk for neutropenia pooled RR, 1. There were no differences in risk for withdrawal due to adverse events, serious adverse events, or other adverse events. A week regimen of triple therapy with telaprevir was associated with higher risk for anemia 3 trials; pooled RR, 1. Triple therapy was also associated with increased risk for thrombocytopenia in 1 trial RR, 1.
One trial found that response-guided therapy with telaprevir for 24 to 48 weeks was associated with higher risk for withdrawal due to adverse events RR, 3. No trial reported harms in patient subgroups. Three trials of dual therapy with pegylated interferon alfa-2b versus alfa-2a for genotype 1 infection reported pooled estimates for harms similar to the estimates based on all trials 21, 30, Duration of follow-up ranged from 3 to 9 years. Ten studies were conducted in Asia 60, 67—72, 75, 77, Eight 64—66, 72, 75—78 were rated as poor-quality and the remainder as fair-quality.
Although all studies reported adjusted risk estimates, only 8 60, 61, 63, 67—70, 73 evaluated 5 key confounders age, sex, genotype, viral load, and fibrosis stage. No study clearly described assessment of outcomes blinded to SVR status. It adjusted for multiple potential confounders, including age, sex, viral load, presence of cirrhosis, multiple comorbid conditions, aminotransferase levels, and others.
It also stratified results by genotype.
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In a predominantly male, Veterans Affairs population, SVR after antiviral therapy was associated with lower risk for all-cause mortality than was no SVR, after a median of 3. Mortality curves began to separate as soon as 3 to 6 months after SVR assessment.
Eighteen other cohort studies also found SVR to be associated with decreased risk for all-cause mortality adjusted hazard ratios, 0. The subgroup of studies that focused on patients with advanced fibrosis or cirrhosis at baseline 62, 63, 65—68, 74—76 or that were conducted in Asia 60, 67—72, 75, 77, 78 reported similar ranges of risk estimates. Antiviral therapy for chronic HCV infection continues to evolve. No study evaluated comparative effectiveness of current antiviral regimens on long-term clinical outcomes. Such trials are a challenge to carry out because of the long time course over which complications of HCV infection develop.
In lieu of direct evidence on long-term clinical outcomes, SVR rates are the primary outcome measure with which to evaluate comparative effectiveness.
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For treatment-naive patients, dual therapy with pegylated interferon alfa-2b is associated with a lower likelihood of SVR than is dual therapy with pegylated interferon alfa-2a absolute difference, about 8 percentage points. Although there was no difference between dual-therapy regimens in risk for withdrawals due to adverse events, pegylated interferon alfa-2b was associated with a lower risk for serious adverse events, suggesting potential tradeoffs between benefits and harms.
Comparative Effectiveness of Treatment for Hepatitis C in Adults
For genotype 2 or 3 infection, standard doses and durations 24 weeks of pegylated interferon as part of dual therapy are more effective than shorter regimens or lower doses, lending support to current dosing guidance 4, 79, Evidence on differential effects of ribavirin dose is limited, although differences were small in most studies. The relative ineffectiveness of dual therapy for genotype 1 infection has led to ongoing efforts to identify more effective treatments.
This has important implications for treatment, as well as for screening, because screening benefits depend in part on the effectiveness of available treatments Triple therapy for genotype 1 infection is also associated with shorter duration of treatment, an important consideration given the high frequency of adverse effects associated with interferon-based therapy.
Across all antiviral regimens, absolute treatment response rates are lower in older patients; black patients; and patients with higher baseline viral load, genotype 1 infection, or more advanced fibrosis. The rapid separation of mortality curves in this study suggests possible residual confounding, given the typically protracted course of HCV infection.
Therefore, estimates of benefit may be exaggerated, although it is not possible to determine to what degree. Eighteen other cohort studies also found that SVR was associated with decreased risk for serious complications of chronic HCV infection, but these studies had more methodological shortcomings than did the Veterans Affairs study. Our study has limitations. We excluded non—English-language articles.
We did not perform formal analyses for publication bias because of the small numbers of trials, but analyses of abstracts and searches of clinical trials registries did not suggest publication bias.
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Estimates and conclusions based on small numbers of trials should also be interpreted cautiously. For example, pooled estimates based on 2 trials can be unreliable, particularly when statistical heterogeneity is present. The trials generally met criteria for efficacy studies, which could limit their applicability because of exclusion of patients with comorbid conditions, and greater adherence than typically observed in clinical practice.
Almost all of the randomized trials were funded by pharmaceutical companies 83, Additional research would help clarify the comparative effectiveness of antiviral treatments. Studies are needed to understand the long-term clinical outcomes associated with different antiviral treatments, the long-term harms of telaprevir and boceprevir, the comparative effectiveness of triple therapy with telaprevir versus boceprevir, and effective strategies to improve adherence Other direct-acting antiviral agents, including second-generation protease inhibitors, polymerase inhibitors, NS5A inhibitors, and others, are in active development, with all-oral, interferon-sparing regimens expected within the next few years The increasing burden of mortality from viral hepatitis in the United States between and National Institutes of Health.
Antiviral activity and tolerability between pegylated interferon alpha 2a and alpha 2b in naive patients with chronic hepatitis C: results of a prospective monocentric randomized trial [Abstract]. Review article: pegylated interferons: chemical and clinical differences. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. Food and Drug Administration. Accessed at www.
A Systematic Review. Prepared by Oregon Evidence-based Practice Center under contract no.