Patient time costs and out-of-pocket costs in hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with substantial costs to patients, their caregivers and society. AIMS: We evaluated time costs (time spent seeking healthcare) and out-of-pocket (OOP) costs for patients with HCV and their caregivers. METHODS: We measured costs for 738 HCV outpatients in a tertiary-care clinic using a patient-completed questionnaire. Time and OOP costs were compared across disease stages and sociodemographic categories. We examined the association between cost and disease stage using linear regression adjusting for age, gender, marital status, education, income and Index of Coexistent Disease (ICED) comorbidity score. Costs were expressed in 2007 Canadian dollars. RESULTS: The mean annual time cost per patient was $2136 (98 h), and ranged from $281 (18 h) in individuals who had cleared the virus to $9416 in transplant recipients (420 h). Caregiver costs were reported in 10% of patients. The mean annual OOP cost per patient was $1326. Patients receiving active treatment and those with late-stage disease spent $2500-2800 per year on HCV-related healthcare, approximately 7% of their annual income. Patients who had cleared the virus had the lowest time and OOP costs. Low income and unemployed patients had higher costs. CONCLUSIONS: In HCV-infected individuals, OOP and time costs represent a significant economic burden and fall disproportionately upon those least able to afford them. The lower cost burden among those who were successfully treated suggests that wider use of antiviral therapy may reduce economic burden in addition to improving health outcomes.

Health utilities and psychometric quality of life in patients with early- and late-stage hepatitis C virus infection.

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection is associated with impairment in health-related quality of life (HRQOL). The purpose of this study was to evaluate HRQOL across the HCV disease spectrum using preference-based (utility) and non-preference-based (psychometric) methods, adjusting for sociodemographic factors and co-morbidity. METHODS: Hepatitis C virus patients (n = 751) were recruited from several tertiary care settings in Vancouver, Canada for this observational, cross-sectional cohort study. Patients completed the Health Utilities Index Mark 2/3, a self-administered time trade-off utility instrument, and the Hepatitis Quality of Life Questionnaire (SF-36 with HCV-specific items). We examined the association between HRQOL and disease stage using linear regression adjusting for age, education, marital status, income, and co-morbidities. RESULTS: Utility scores were low across disease stage and instrument, ranging from 0.51 to 0.80. On the SF-36, the mean Physical Component Summary score ranged from 37.2 to 49.2 across disease stage, and the Mental Component Summary score ranged from 39.7 to 45.7 (United States norms = 50). In general, patients with viral clearance had the highest scores, and those with late-stage disease (cirrhosis, liver cancer) had the lowest. Multivariable linear regression showed that the effect of disease stage was modest overall. Increasing age, lower income, unattached marital status, and high comorbidity were strongly associated with impairment in HRQOL. CONCLUSIONS: The effect of stage of disease on HRQOL is modest, although viral clearance is associated with higher HRQOL. HCV patients' HRQOL is strongly associated with concomitant illness and sociodemographic factors.

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial.

BACKGROUND: Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. METHODS: In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1.5 mug/kg plus ribavirin 800-1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400-1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670. FINDINGS: Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44-64], p=0.013 for PRB28; 58/103 [56%, 44-66], p=0.005 for PR4/PRB24; 69/103 [67%, 57-76], p<0.0001 for PRB48; and 77/103 [75%, 65-83], p<0.0001 for PR4/PRB44; vs 39/104 [38%, 28-48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%] vs 35/104 [34%]) and dysgeusia (111/416 [27%] vs nine of 104 [9%]) than did the control group. INTERPRETATION: In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. FUNDING: Merck.

Evaluation of VCH-759 monotherapy in hepatitis C infection.

BACKGROUND/AIMS: VCH-759 is a non-nucleoside inhibitor of HCV RNA-dependent polymerase with sub-micromolar IC(50) values versus genotype 1a/1b replicons. METHODS: The antiviral activity, pharmacokinetics and tolerability of VCH-759 administered as monotherapy for 10 days with a 14 day follow-up period were evaluated in 31 treatment-nai ve genotype 1 participants. Three cohorts received: 400mg thrice (t.i.d.), 800 mg twice (b.i.d.), 800 mg t.i.d or placebo. RESULTS: VCH-759 was well tolerated with the most frequent adverse event being gastrointestinal upset in both the active and placebo groups attributable, in part, to the dosing vehicle. VCH-759 was rapidly absorbed and trough plasma levels were at or above the IC(90) (non protein-adjusted) for all dosing regimens. The mean maximal decrease in HCV RNA log(10) (IU/mL) was 1.97, 2.30 and 2.46 for 400mg t.i.d., 800 mg b.i.d. and 800 mg t.i.d. doses. Viral polymerase genotypic sequencing revealed emergence of HCV variants in a majority of participants that coincided with on-treatment viral rebound. CONCLUSIONS: VCH-759 was well tolerated and achieved a> or =2 log(10) decline in HCV RNA with 800 mg b.i.d. and t.i.d doses. In a subset of participants, viral rebound was observed and associated with resistant variants. This data supports further evaluation of VCH-759 in combination with interferon-ribavirin treatment.

Sustained responders have better quality of life and productivity compared with treatment failures long after antiviral therapy for hepatitis C.

OBJECTIVES: We sought to compare the health status of patients with a sustained response to antiviral therapy for hepatitis C virus (HCV) infection with that of treatment failures, using health-related quality of life and preference (utility) measures. METHODS: Sustained responders had undetectable HCV viral levels 6 months after antiviral therapy. After antiviral therapy, participants completed, by mail or interview, the hepatitis-specific Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), the Health Utilities Index Mark 2/3 (HUI2/3), and time trade-off (TTO) for current health. The respondents provided information on demographics, history of substance abuse, comorbidities, and health history. Detailed clinical information was obtained by chart review. The respondents also indicated whether they missed work, volunteer opportunities, or household activities during the previous 3 months because of hepatitis C infection or its treatment. RESULTS: A total of 235 patients (133 responders and 102 treatment failures) completed questionnaires at an average of 3.7 years after the end of treatment. Treatment failures had significantly lower scores on the eight SF-36 domains (P<0.01), lower scores on the hepatitis-specific domains (P<0.0001), and lower physical (42.5 vs. 49.2) and mental (40.5 vs. 46.1) component summary scores (P<0.01). HUI3 (0.57 vs. 0.70), HUI2 (0.74 vs. 0.80), SF-6D (0.65 vs. 0.71), and TTO (0.84 vs. 0.89) were lower for treatment failures (P<0.05). The regression-adjusted difference in HUI3, SF-6D, physical summary score, and mental summary score was 0.08 (P=0.04), 0.05 (P=0.004), 5.22 (P=0.001), and 5.73 (P<0.0001), respectively. Differences in the HUI2 and TTO scores were not significant after adjustment for demographic and clinical variables. Treatment failures were more likely to have missed work, volunteer opportunities, or household activities in the previous 3 months because of hepatitis C infection or its treatment (44 vs. 9%, P<0.001). CONCLUSIONS: Patients with a sustained response to antiviral therapy for chronic HCV infection have better quality of life than treatment failures do. Our study validates the benefits associated with the sustained response to antiviral therapy in a real-world clinic population and shows that these benefits are maintained over the long term.

Does cirrhosis affect quality of life in hepatitis C virus-infected patients?

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and is associated with impairments in health-related quality of life. AIMS: To evaluate quality of life (QOL) in cirrhotic (compensated and decompensated) and non-cirrhotic patients with chronic HCV infection, using preference-based (utilities) and non-preference-based methods of evaluating QOL. METHODS: In a tertiary care setting, 271 patients completed a self-administered time trade-off utility instrument, the Health Utility Index Mark 2 and Mark 3, and the Hepatitis Quality of Life Questionnaire Version 2. Mean QOL scores were compared across HCV disease stages and sociodemographical categories. We examined the association between QOL and disease stage using linear regression adjusting for age, education, marital status, log income and Charlson comorbidity scores. Mean utility scores were compared across disease stages using a propensity score method. RESULTS: Mean utilities were lower than general population norms (0.81-0.92) and ranged from 0.62 to 0.82 in non-cirrhotic patients (n=197), 0.56-0.84 in compensated cirrhotic patients (n=17) and 0.55-0.76 for decompensated cirrhotic patients (n=57). No significant association found was between disease stage and utility for current health status. Higher income, fewer comorbidities and living in a married or common-law relationship were significantly associated with higher utilities and better QOL. No significant difference in utilities was found between disease stages using propensity score matching. CONCLUSIONS: Our study confirms that changes in HCV disease stage explain only small changes in QOL and suggests that factors such as underlying comorbidities, income and marital status have a greater effect on QOL than disease stage.

Infliximab maintenance therapy for fistulizing Crohn's disease.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection.

BACKGROUND & AIMS: Entecavir is a novel and selective nucleoside analogue with potent activity against hepatitis B virus (HBV). METHODS: In a 24-week, double-blind, randomized, multicenter, phase II clinical trial, the safety and efficacy of entecavir (0.01 mg/day, 0.1 mg/day, or 0.5 mg/day orally) were compared with lamivudine (100 mg/day orally). Patients (n = 169) chronically infected with HBV (hepatitis B e antigen [HBeAg]-positive and -negative) were evaluated for efficacy. RESULTS: Compared with lamivudine, entecavir reduced HBV DNA by an additional 0.97 log(10) at the 0.1-mg/day dose and an additional 1.28 log(10) at the 0.5-mg/day dose (P < 0.0001). A clear dose-response relationship was observed for entecavir with the higher doses showing significantly greater viral suppression. In patients treated with entecavir 0.5 mg/day, 83.7% had an HBV-DNA level below the lower limit of detection of the Quantiplex branched DNA (bDNA) assay (Bayer-Versant Diagnostics, formerly Chiron Diagnostics, Emeryville, CA), compared with 57.5% treated with 100 mg/day lamivudine (P = 0.008). In both treatment arms, very few patients achieved HBeAg loss and/or seroconversion by week 22. More patients treated with the 0.1-mg/day and 0.5-mg/day doses of entecavir had normalization of alanine transaminase (ALT) levels at week 22 compared with lamivudine (P = not significant). Entecavir was well tolerated; most adverse events were mild to moderate, transient, and comparable in all study arms. CONCLUSIONS: This study showed that entecavir has potent antiviral activity against HBV at 0.1-mg/day and 0.5-mg/day doses, both of which were superior to lamivudine in chronically infected HBV patients.