The Effect of Shorter Treatment Regimens for Hepatitis C on Population Health and Under Fixed Budgets

Abstract

Background: Direct acting antiviral hepatitis C virus (HCV) therapies are highly effective but costly. Wider adoption of an 8-week ledipasvir/sofosbuvir treatment regimen could result in significant savings, but may be less efficacious compared with a 12-week regimen. We evaluated outcomes under a constrained budget and cost-effectiveness of 8 vs 12 weeks of therapy in treatment-naïve, noncirrhotic, genotype 1 HCV-infected black and nonblack individuals and considered scenarios of IL28B and NS5A resistance testing to determine treatment duration in sensitivity analyses.

Methods: We developed a decision tree to use in conjunction with Monte Carlo simulation to investigate the cost-effectiveness of recommended treatment durations and the population health effect of these strategies given a constrained budget. Outcomes included the total number of individuals treated and attaining sustained virologic response (SVR) given a constrained budget and incremental cost-effectiveness ratios.

Results: We found that treating eligible (treatment-naïve, noncirrhotic, HCV-RNA <6 million copies) individuals with 8 weeks rather than 12 weeks of therapy was cost-effective and allowed for 50% more individuals to attain SVR given a constrained budget among both black and nonblack individuals, and our results suggested that NS5A resistance testing is cost-effective.

Conclusions: Eight-week therapy provides good value, and wider adoption of shorter treatment could allow more individuals to attain SVR on the population level given a constrained budget. This analysis provides an evidence base to justify movement of the 8-week regimen to the preferred regimen list for appropriate patients in the HCV treatment guidelines and suggests expanding that recommendation to black patients in settings where cost and relapse trade-offs are considered.

Keywords: IL28B; NS5A; budget impact; cost-effectiveness.

Figure 1.

Decision tree evaluating 8-week vs 12-week therapy for HCV. Figure 1 is a schematic of our model. All individuals begin the analysis ready for treatment. Following firstline therapy, individuals’ chance of attaining SVR is based on the efficacy of the firstline regimen. Among those failing to achieve SVR, they are either retained in care or lost to follow-up. Those lost to follow-up never achieve SVR. Those retained are treated with salvage therapy and attain SVR with a probability equal to the efficacy of the salvage therapy. At the end of each branch (SVR or no SVR), lifetime cost and QALY outcomes are calculated via the HEP-CE model. Abbreviations: HCV, hepatitis C virus; HEP-CE, Hepatitis C Cost-Effectiveness Model; QALY, quality-adjusted life-year; SVR, sustained virologic response.

Figure 2.

Sensitivity analysis of SVR of 8-week therapy and salvage therapy. Figure 2 depicts the results of our sensitivity analysis of the effect of 8-week regimen SVR and salvage therapy SVR. The x-axis displays the SVR range of the salvage regimen, and the y-axis depicts the SVR of the 8-week regimen. Holding constant the efficacy of the 12-week regimen, we vary the salvage SVR from 0% to 100% and find the corresponding 8-week regimen efficacy threshold that results in 12-week therapy to be preferred. In the figure, the downward sloping line is that threshold, with the shaded region underneath representing where the 12-week regimen is preferred. Areas above each threshold shaded region indicate where the 8-week regimen is preferred. The threshold for black patients is higher compared with nonblack patients because in our primary data source [18] the 12-week efficacy of LDV/SOF was higher among black patients (98.9%) than it was among nonblack (97.1%) patients, which makes 12 weeks of therapy more attractive in general. Abbreviations: LDV, ledipasvir; SOF, sofosbuvir; SVR, sustained virologic response.