Full Text Article - Newer medications can cure HCV infections

March 22, 2017
Media Coverage of this Article
Hepatitis C Cures Lag While New Drugs Wait in the Wings

By Jessica Wapner

But with numerous DAAs now available—along with their long trail of clinical trial data—primary care physicians are left to navigate a crowded and confusing landscape for treating HCV. Controversy surrounding the cost of these drugs has also become a concern..

March 8, 2017

Newer medications can cure HCV infections
A new analysis reveals a dramatic transformation in the care of patients infected with hepatitis C virus (HCV) as more effective and tolerable medications have become available.

In an analysis of all HCV antiviral treatment regimens (N=107,079) initiated from 1999 through 2015 in the US Veterans Affairs national healthcare system, cure rates increased steadily from 19.2% in 1999 to 36.0% in 2010 before a remarkable increase to 90.5% in 2015. The number of patients achieving sustained virologic response was 1313 in 2010, the last year of the interferon era and increased 5.6-fold to 7377 in 2014 and 21-fold to 28,084 in 2015.

"The introduction of effective direct antiviral agents together with the allocation of appropriate funds and resources allowed the VA healthcare system to treat and cure hepatitis C in unprecedented numbers. In fact, out of approximately 57,500 patients cured of hepatitis C in the VA since 1999, approximately half were cured in a single year in 2015," said. Dr. George Ioannou, senior author of the Alimentary Pharmacology and Therapeutics analysis. "The question is whether we are delivering these medications to the patients who need them and what obstacles there are to treating and curing the majority of hepatitis C infected patients."
Source

March 15, 2017
Medscape Medical News
Dramatic Increase in HCV Cure Rate Among Veterans
Jennifer Garcia
| March 15, 2017
Use of direct-acting antiviral drugs (DAAs) has led to a 21-fold increase in the cure rate for hepatitis C virus (HCV) infections among patients treated in the Veterans Affairs (VA) healthcare system between 1999 and 2015, according to a new study.

"Considering that HCV infection is the most common cause of cirrhosis and liver cancer in the VA and the United States, that the benefits of SVR are long-lasting and that HCV clearance reduces the risk of liver cancer by 76% and all-cause mortality by 50%, the potential public health benefits of large-scale HCV treatment are great," write Dr Ioannou and colleagues.
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Alimentary Pharmacology and Therapeutics
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Transformation of hepatitis C antiviral treatment in a national healthcare system following the introduction of direct antiviral agents
A. M. Moon,P. K. Green,K. Berry,G. N. Ioannou
First published: 8 March 2017
DOI: 10.1111/apt.14021

Summary
Background
Highly effective direct antiviral agents (DAAs) for hepatitis C virus (HCV) were introduced recently. Their utilisation has been limited by high cost and low access to care.

Aim
To describe the effect of DAAs on HCV treatment and cure rates in the United States Veterans Affairs (VA) national healthcare system.

Methods
We identified all HCV antiviral treatment regimens initiated from 1 January 1999 to 31 December 2015 (n = 105 369) in the VA national healthcare system, and determined if they resulted in sustained virological response (SVR).

Results

HCV antiviral treatment rates were low (1981–6679 treatments/year) in the interferon era (1999–2010). The introduction of simeprevir and sofosbuvir in 2013 and ledipasvir/sofosbuvir and paritaprevir/ombitasvir/ritonavir/dasabuvir in 2014 were followed by increases in annual treatment rates to 9180 in 2014 and 31 028 in 2015. The number of patients achieving SVR was 1313 in 2010, the last year of the interferon era, and increased 5.6-fold to 7377 in 2014 and 21-fold to 28 084 in 2015. The proportion of treated patients who achieved SVR increased from 19.2% in 1999 and 36.0% in 2010 to 90.5% in 2015. Within 2015, monthly treatment rates ranged from 727 in July to 6868 in September correlating with the availability of funds for DAAs.

Conclusions

DAAs resulted in a 21-fold increase in the number of patients achieving HCV cure. Treatment rates in 2015 were limited primarily by the availability of funds. Further increases in funding and cost reductions of DAAs in 2016 suggest that the VA could cure the majority of HCV-infected Veterans in VA care within the next few years.

Discussion Only

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Our results demonstrate a dramatic transformation in HCV care as more effective and tolerable interferon-free DAAs have emerged. Over the last 2 years of our study period (2014–15), the VA healthcare system has significantly scaled up its provision of HCV antiviral treatment. SVR rates in our cohort increased steadily from 19.2% in 1999 to 36.0% in 2010 before a remarkable increase to 90.5% in 2015, including 91.7% among genotype 1-infected patients, which is comparable with SVR rates reported in the clinical trials of LDV/SOF (94–99%)[2-4] and PrOD (95–100%).[5, 7-9] As a result, the number of patients achieving SVR increased 21-fold from 1313 in 2010 to an estimated 28 084 in 2015. The number of patients cured in 2015 (n = 28 084) represented almost half of all patients cured in the entire 17-year period (n = 57 445). Our results suggest that with increased funding and reduced cost of DAAs, both of which already occurred in January 2016, the VA will have the ability to successfully treat the majority of the remaining 124 662 HCV-infected Veterans who were in the VA care as of January 2016 within the next few years.[29]

Several factors likely contributed to the remarkable increases in HCV treatment and cure rates that occurred in 2014 and 2015. Most importantly, the introduction of interferon-free DAAs vastly increased the VA population eligible for and willing to undergo antiviral treatment. Second, given the high relative cost of DAAs, increases in the VA funding were critical. Third, the VA embraced innovative care models including the use of teleconsultation for HCV treatment.[30] Through the Specialty Care Access Network-Extension for Community Healthcare Outcomes (SCAN-ECHO) program, which allows physicians, nurses and pharmacists to get teaching and feedback through videoconferencing from HCV experts, median time from diagnosis to treatment has decreased from more than 2 years to 6 months.[31] Finally, the VA used existing electronic databases to identify and coordinate care for HCV-infected Veterans, employed aggressive screening practises for HCV and encouraged local facilities to set ambitious treatment goals. These goals were facilitated by a national integrated hepatitis C program, which oversees and supports dedicated hepatitis C teams at every VA facility.[32]

Although a record number of highly effective antiviral regimens were prescribed in 2015 (n = 31 028), this still represented only a small proportion of all HCV-infected patients in the VA care. The number of patients who received HCV antiviral treatment could, in theory, be limited by the availability of funds for DAAs, the cost of DAAs, access to experienced treatment providers, identification and linkage to care of eligible HCV-infected patients and willingness of patients to undergo treatment. The nine-fold variation in monthly treatment rates in FY 2015 related to availability of DAA funding suggests that funding for HCV treatment was the most important determinant of treatment rates in 2015 (Figure 4).

Whilst the increases in HCV treatment and cure rates in 2014 and 2015 were impressive, there are reasons to believe that these rates will increase even further in 2016. First, in January 2016, the US Congress approved $1.5 billion for HCV DAA costs in the VA in FY 2016, doubling the funding from FY 2015.[33] Second, the VA was able to purchase LDV/SOF and PrOD in 2016 at approximately half the price paid in 2015.[31, 34] Third, the FDA approval of additional antiviral agents including daclatasvir (approved 24 July 2015), elbasvir/grazoprevir (approved 28 January16) and velpatasvir/sofusbuvir (approved 28 June 2016) will lead to increased treatment and cure rates, particularly for genotype 2 and 3-infected patients who have fewer treatment options and lower SVR rates than genotype 1-infected patients. Finally, the VA employed prioritisation criteria until February 2016, encouraging facilities and providers to give priority to the treatment of patients with advanced fibrosis or cirrhosis, those likely to have rapid progression of fibrosis and those with extrahepatic manifestations of HCV.[35] However, as of February 2016, the VA removed all HCV treatment prioritisation criteria and encouraged treatment of all patients, whilst continuing to emphasise aggressive outreach to patients with advanced fibrosis or cirrhosis.[36] This should further increase treatment rates and is in stark contrast to most healthcare systems, state Medicaid programs and insurance carriers in the US, which still restrict access to DAAs based on severity of liver disease. Following the VA's lead, state Medicaid programs in New York, Washington, Delaware, Florida and Massachusetts announced the removed restrictions on the coverage of DAAs. Also the AASLD Guidance documents, which in 2015 stated that it was ‘most appropriate to treat those at greatest risk of disease complications before treating those with less advanced disease’, were changed in 2016 stating that ‘treatment is recommended for all patients with chronic HCV infection.’[37]

Questions have been raised about the feasibility of large-scale HCV treatment efforts given the high costs of new HCV medications.[38] Some have concluded that whilst eliminating chronic HCV infection is possible, the required universal access to DAAs is not currently feasible.[39] Yet, many of the obstacles of large-scale HCV treatment are not shared by the VA. It is a large, federally funded healthcare system with the ability to negotiate lower medication prices, offer DAAs to patients for free or for a nominal co-pay, obtain influxes of funding in response to demand for DAAs and identify all HCV-diagnosed patients using its comprehensive national electronic medical records. Given these advantages and our data until 2015, the possibility of near universal cure of HCV appears realisable within the VA population. Considering that HCV infection is the most common cause of cirrhosis and liver cancer in the VA and the United States,[21] that the benefits of SVR are long-lasting[40] and that HCV clearance reduces the risk of liver cancer by 76% and all-cause mortality by 50%, the potential public health benefits of large-scale HCV treatment are great.[41-46] In addition, a recent cost-effectiveness analysis reported that DAAs must cost $47 000 per treatment course to achieve incremental cost-effectiveness ratio of $50 000 per QALY for patients with no fibrosis,[47] suggesting that it would be cost-effective or even cost saving[48] for the VA to treat all HCV-infected Veterans.[47] Another recent cost-effectiveness analysis reported that, using wholesale acquisition costs, all-oral DAA regimens such as the LDV/SOF were associated with the lowest yearly costs per SVR and was the most cost-effective option in patients with genotype 1 infection.[49]

This study has a few potential limitations. SVR values were missing in 9.6% of all patients, many of whom initiated antiviral treatment in the latter half of 2015 and had not yet accumulated sufficient follow-up time to ascertain SVR (Table S11). Missing SVR values were imputed using era-specific logistic regression models that included multiple baseline predictors of SVR as well as duration of treatment and antiviral regimen, which increases confidence that the estimated SVR rates are accurate. The magnitude of increases in treatment and cure rates that we report in the VA may not be directly generalisable to the non-Veteran US population for many of the previously mentioned reasons including that some payers have introduced prior authorisation rules limiting HCV treatment to those with advanced liver fibrosis.[50, 51] Although we report dramatic increases in treatment rates temporally related to the introduction of DAAs and to the availability of funding for DAAs especially in 2015 (Figure 4), our study was not designed to formally evaluate other factors that may influence treatment rates such as staffing, infrastructure, administration, training, identification of patients and linkage to care. With the funding increases and DAA price reductions that occurred in 2016, such factors may very well become the limiting factors determining treatment rates in the near future.

In conclusion, the VA health care system has dramatically increased the number of HCV treatments initiated and resulting instances of SVR in 2015. The acceleration in treatment provision, particularly in August and September 2015, demonstrates the abilities of the VA's existing HCV treatment infrastructure when sufficient funding for DAAs is available. These results raise the spectre of near complete eradication of HCV within the VA system, which given the 124 662 VA patients with diagnosed HCV, would substantially reduce the burden of HCV within the entire country and prevent tens of thousands of deaths.

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