Hepatitis C virus re-treatment in the era of direct-acting antivirals: projections in the USA

Alimentary Pharmacology and Therapeutics

ORIGINAL ARTICLE
Hepatitis C virus re-treatment in the era of direct-acting antivirals: projections in the USA
Authors J. Chhatwal, Q. Chen, T. Ayer, E. D. Bethea, F. Kanwal, K. V. Kowdley, X. Wang, M. S. Roberts, S. C. Gordon

First published: 29 January 2018

Summary
Background
The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re-treatment is important for budget impact and disease burden projections.

Aim
To quantify the number of HCV patients who fail to achieve SVR on oral DAAs (NS5A vs. non-NS5A) and require re-treatment.

Methods
We used a mathematical model to simulate clinical management of HCV in the USA, which included the implementation of HCV screening, treatment, and disease progression. We simulated different waves of DAA treatment and used real-world data to extract SVR rates and market shares of available therapies.

Results
Our model projected that the number of people living without viraemia (i.e. cured) would increase from 0.70 million in 2014 to 1.78 million by 2020. Between 2014 and 2020, 1.50 million people would receive treatment with DAAs, of whom 124 000 (8.3%) are projected to fail to achieve SVR. Among those treatment failures, 66 600 (53.7%) patients would fail treatment with NS5A inhibitors and 69 600 (56.1%) would have cirrhosis. During the same period, 34 200 people would progress to decompensated cirrhosis and 27 300 would develop hepatocellular carcinoma after failing to achieve SVR.

Conclusions
Even in the era of highly effective DAAs, a significant number of patients will fail to achieve SVR and will require re-treatment options. Timely and effective re-treatment is essential to prevent the long-term sequelae of HCV.

DISCUSSION

Full text article online: http://onlinelibrary.wiley.com/doi/10.1111/apt.14527/full

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The availability of well-tolerated and highly effective DAAs offers a new hope to eliminate HCV as a public health threat. However, even with the newer generations of DAAs, a small proportion of patients will fail to achieve SVR and could develop advanced sequelae such as decompensated cirrhosis and HCC. In this study, we simulated the current clinical landscape of HCV treatment and projected the number of patients in the USA who would receive treatment, achieve SVR, or require re-treatment. We found that in the era of DAAs, a total of 1.50 million people would receive treatment between 2014 and 2020 and around 124 000 (8.3%) would fail to achieve SVR; the majority of those who fail treatment would have been exposed to NS5A inhibitors. Timely and effective retreatment of these patients could prevent the long-term sequelae of HCV.

Earlier studies have estimated the number of patients who would remain viraemic in the era of DAAs,[6] and projected disease burden under different screening and treatment scenarios.[5, 6, 25, 26] This study adds new information by estimating the number of patients who would fail to achieve SVR, especially with NS5A inhibitors, and require retreatment in the era of DAAs. Providing this data allows payers to assess the budget impact of HCV treatment and disease burden projections. Although the DAAs have been shown to be cost-effective/saving,[27, 28] budget needed to treat all HCV patients remains challenging in some settings.[29]

We observed that under current clinical practice, the number of patients receiving treatment would drop to 61 000 by 2020 in spite of the fact that around 844 000 patients would still be viraemic in that year. This is because the majority of viraemic patients aware of their status would have received treatment by this time, whereas, those unaware of their HCV status would not be able to avail the benefits of DAA therapy. This finding emphasises the need to update the current screening policies to diagnose patients who otherwise would remain unaware and untreated. In addition, there is a need to remove treatment barriers for patients who are already aware of their HCV status but not yet linked to care, such as many injection drug users and people in prisons.

National and global health policy initiatives have stressed the desirability of eliminating HCV as a public health threat by 2030. To achieve this goal, a comprehensive strategy of patient identification, linkage to care and treatment access is required.[30] In addition, the availability of effective treatment options for patients who fail to achieve SVR after initial therapy is necessary. Although the number of such patients is relatively small compared with the current burden of HCV, these patients could become a nonsignificant portion of the viraemic population in the future. Successful retreatment of these patients, who are already linked to care, could reduce the risk of long-term clinical sequelae. While viral clearance would prevent development of advanced sequelae from chronic HCV, other external factors such as abuse of alcohol or drugs would also need to be addressed via appropriate interventions to achieve the full benefits of viral clearance with DAA therapy.

Our study also shows a growing population of patients alive following HCV cure. As this patient population increases, disease management efforts focused on regular surveillance of persons with pre-treatment advanced fibrosis or cirrhosis is important, as they remain at risk of developing hepatocellular carcinoma.[31] In addition, the burden of management for these patients may also shift from specialists to general practitioners. If this transition does take place, future efforts should also focus on increasing the awareness among general practitioners and internists regarding appropriate medical care for patients cured of HCV.

This modelling-based study has some limitations. First, the analysis only included non-institutionalised HCV-infected persons as estimated by the NHANES studies. Therefore, our results likely underestimated the number of viraemic patients. Secondly, recent data suggest that the uptake of birth-cohort screening in practice remains low, therefore, our model may have over-estimated the number of patients who would become aware of their HCV status. Thirdly, we did not include in the model HIV-HCV co-infection, which is beyond the scope of the current work. Fourth, we did not consider the possibility of regression of fibrosis after SVR, which is unlikely to effect the results presented in this study. Finally, we made assumptions about future treatment capacity, which could vary over time.

In conclusion, we found that even in the era of highly effective DAAs, there are still going to be challenges. To achieve HCV elimination a national strategy will need to support the development of systems aimed at increasing the diagnosis of HCV and plans outlining the effective and timely retreatment of patients who have failed on DAAs.

Read full text article online: http://onlinelibrary.wiley.com/doi/10.1111/apt.14527/full
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