A new paradigm evaluating cost per cure of HCV infection in the UK

Background: New interferon (IFN)-free treatments for hepatitis C are more effective, safer but more expensive than current IFN-based therapies. Comparative data of these, versus current first generation protease inhibitors (PI) with regard to costs and treatment outcomes are needed. We investigated the real-world effectiveness, safety and cost per cure of 1st generation PI-based therapies in the UK. Methods: Medical records review of patients within the HCV Research UK database. Patients had received treatment with telaprevir or boceprevir and pegylated interferon and ribavirin (PR). Data on treatment outcome, healthcare utilisation and adverse events (AEs) requiring intervention were collected and analysed overall and by subgroups. Costs of visits, tests, therapies, adverse events and hospitalisations were estimated at the patient level. Total cost per cure was calculated as total median cost divided by SVR rate. Results: 154 patients from 35 centres were analysed. Overall median total cost per cure was £44,852 (subgroup range,: £35,492 to £107,288). Total treatment costs were accounted for by PI: 68.3 %, PR: 26.3 %, AE management: 5.4 %. Overall SVR was 62.3 % (range 25 % to 86.2 %). 36 % of patients experienced treatment-related AEs requiring intervention, 10 % required treatment-related hospitalisation. Conclusions: This is the first UK multicentre study of outcomes and costs of PI-based HCV treatments in clinical practice. There was substantial variation in total cost per cure among patient subgroups and high rates of treatment-related discontinuations, AEs and hospitalisations. Real world safety, effectiveness and total cost per cure for the new IFN free combinations should be compared against this baseline

Is increased hepatitis C virus case-finding combined with current or 8-week to 12-week direct-acting antiviral therapy cost-effective in UK prisons? A prevention benefit analysis

UNLABELLED: Prisoners have a high prevalence of hepatitis C virus (HCV), but case-finding may not have been cost-effective because treatment often exceeded average prison stay combined with a lack of continuity of care. We assessed the cost-effectiveness of increased HCV case-finding and treatment in UK prisons using short-course therapies. A dynamic HCV transmission model assesses the cost-effectiveness of doubling HCV case-finding (achieved through introducing opt-out HCV testing in UK pilot prisons) and increasing treatment in UK prisons compared to status quo voluntary risk-based testing (6% prison entrants/year), using currently recommended therapies (8-24 weeks) or interferon (IFN)-free direct-acting antivirals (DAAs; 8-12 weeks, 95% sustained virological response, £3300/week). Costs (British pounds, £) and health utilities (quality-adjusted life years) were used to calculate mean incremental cost-effectiveness ratios (ICERs). We assumed 56% referral and 2.5%/25% of referred people who inject drugs (PWID)/ex-PWID treated within 2 months of diagnosis in prison. PWID and ex-PWID or non-PWID are in prison an average 4 and 8 months, respectively. Doubling prison testing rates with existing treatments produces a mean ICER of £19,850/quality-adjusted life years gained compared to current testing/treatment and is 45% likely to be cost-effective under a £20,000 willingness-to-pay threshold. Switching to 8-week to 12-week IFN-free DAAs in prisons could increase cost-effectiveness (ICER £15,090/quality-adjusted life years gained). Excluding prevention benefit decreases cost-effectiveness. If >10% referred PWID are treated in prison (2.5% base case), either treatment could be highly cost-effective (ICER<£13,000). HCV case-finding and IFN-free DAAs could be highly cost-effective if DAA cost is 10% lower or with 8 weeks' duration. CONCLUSIONS: Increased HCV testing in UK prisons (such as through opt-out testing) is borderline cost-effective compared to status quo voluntary risk-based testing under a £20,000 willingness to pay with current treatments but likely to be cost-effective if short-course IFN-free DAAs are used and could be highly cost-effective if PWID treatment rates were increased. (Hepatology 2016;63:1796-1808)

Increasing uptake of Hepatitis C virus infection case-finding, testing and treatment in primary care:HepCATT (Hepatitis C Assessment Through to Treatment Trial) qualitative evaluation

Hepatitis C virus (HCV) infection is a key cause of liver disease but can be cured in more than 95% of patients. Around 70 000 people in England may have undiagnosed HCV infection and many more will not have been treated. Interventions to increase case-finding in primary care are likely to be cost-effective; however, evidence of effective interventions is lacking. The Hepatitis C Assessment Through to Treatment (HepCATT) trial assessed whether a complex intervention in primary care could increase case-finding, testing, and treatment of HCV

Geographical variation in Hepatitis C-related severe liver disease and patient risk factors: A multicentre cross-sectional study

No abstract available

How do people in prison feel about opt-out hepatitis C virus testing?

The prison population is central to the campaign to eliminate hepatitis C virus as a public health threat. In the UK, this has led to the introduction of a national ‘opt‐out’ policy, requiring people in prison to be tested for HCV unless they decline, with a target to test 75% of those admitted. However, in a representative prison estate in the East Midlands of England (20,000 prison entrants per annum) testing rates were only 13.4%. This qualitative study explains why the rates of test uptake are so far short of target. This qualitative study examines the experiences of 45 people in prison about hepatitis C virus testing in an English category C (low security) prison. The data collection method was semi‐structured interviews. The data were coded and analysed according to the research questions, and interpretation of the data was aided by the use of a thematic network approach. The themes Fear , Insufficient Knowledge, Stigma, Privacy , Choice and Prison Life emerged as the principal barriers to test uptake. Test Uptake Facilitators that promoted testing were identified by participants and benefits presented of prison health care being a Health Farm . In order to increase hepatitis C virus test uptake, significant changes and flexibility in the timing, location, and staff deployed to test are required. Providing information to people in prison about hepatitis C virus transmission and treatment may reduce fears and enable the test uptake target to be met and sustained

Synthesis of nucleoside-boronic esters hydrophobic pro-drugs: a possible route to improve hydrophilic nucleoside drug loading into polymer nanoparticles

Nucleoside analogues are active therapeutic agents for different types of diseases e.g. Cancer and virus infections. However, they are associated with several side effects due to off-target accumulation. Particulate delivery systems such as nanoparticles (NP) may be able to selectively target drug into affected organs and lower or omit off-target accumulation. Hydrophilic nucleoside analogues are poorly incorporated into NP. This work has used boronic compounds to synthesize more hydrophobic biodegradable pro-drugs of hydrophilic nucleosides to improve drug loading into NP. Ribavirin (RV) was used as a model hydrophilic nucleoside to test our hypothesis. RV is a broad antiviral agent, active against both RNA and DNA viruses. RV accumulates into Red Blood Cells (RBCs) causing haemolytic anaemia that restricts its therapeutic benefits. RBCs are reported to have no endocytic mechanisms. So, NP delivery should be advantageous. Two hydrophobic pro-drugs of RV were synthesized namely, ribavirin conjugated to phenylboronic acid and ribavirin conjugated to 4-butoxy-3, 5-dimethylphenylboronic acid and were encapsulated into polymer NP. It was shown that the pro-drugs were incorporated more effectively into polymer nanoparticles with a 1700 fold improved RV loading. Polymer NP had been prepared with biocompatible and biodegradable polymers, Poly(glycerol adipate) and its more hydrophobic derivatives

Use of short-tandem repeat (STR) fingerprinting to validate sample origins in hepatitis C virus molecular epidemiology studies

Sequence analysis is used to define the molecular epidemiology and evolution of the hepatitis C virus. Whilst most studies have shown that individual patients harbour viruses that are derived from a limited number of highly related strains, some recent reports have shown that some patients can be co-infected with very distinct variants whose frequency can fluctuate greatly. Whilst co-infection with highly divergent strains is possible, an alternative explanation is that such data represent contamination or sample mix-up. In this study, we have shown that DNA fingerprinting techniques can accurately assess sample provenance and differentiate between samples that are truly exhibiting mixed infection from those that harbour distinct virus populations due to sample mix-up. We have argued that this approach should be adopted routinely in virus sequence analyses to validate sample provenance

Use of a regional wall motion score to enhance risk stratification of patients receiving an implantable cardioverter-defibrillator

AbstractObjectives. We postulated that preoperative assessment of both regional wall motion and left ventricular ejection fraction would serve as an accurate prognostic indicator of long-term cardiac mortality and functional outcome in patients treated with an implantable cardioverter-defibrillator.Background. Long-term cardiac mortality has remained high in patients receiving an implantable cardioverter-defibrillator. The ability to risk stratify patients before defibrillator implantation is becoming increasingly important from a medical and economic standpoint.Methods. The hypothesis was retrospectively tested in 74 patients who had received an implantable cardioverterdefibrillator. Left ventricular ejection fraction and regional wall motion score, derived from centerline chord motion analysis, were calculated for each patient from the preoperative right anterior oblique contrast ventriculogram. Wall motion score was the only significant independent predictor of long-term cardiac mortality and functional status by multivariate analysis because of its enhanced prognostic capability in patients with an ejection fraction in the critical range of 30% to 40%.Results. Patients with an ejection fraction >40% had a 3-year cardiac mortality rate of 0% compared with 25% for those with an ejection fraction of 30% to 40% and 48% for those with an ejection fraction <30% (p < 0.05). Similarly, 75% of patients with an ejection fraction >40% were in New York Heart Association functional class I or II during long-term follow-up compared with 59% of those with an ejection fraction 30% to 40% and 29% of those with an ejection fraction <30%. Among patients with an ejection fraction of 30% to 40%, those with a wall motion score >16% had a 3-year cardiac mortality rate of 0% compared with 71% of those with a wall motion score ≤ 16% (p = 0.002). In addition, 86% of patients with a wall motion score >16% were in functional class I or II during long-term follow-up compared with 13% of those with a wall motion score ≤16% (p = 0.001).Conclusions. Long-term cardiac mortality and functional outcome in patients receiving an implantable cardioverterdefibrillator can be predicted if the left ventricular ejection fraction and regional wall motion score are measured preoperatively