In May 2011, the United States Food and Drug Administration (FDA) approved the direct-acting antiviral (DAA) drugs boceprevir (BOC) and teleprevir (TVR) to be used in combination with peginterferon and ribavirin (PEG/RBV) for genotype 1 (G1) chronic hepatitis C (HCV). These drugs offered improvements in efficacy and reduced duration for some patients, benefits somewhat compromised by increased adverse events and pill burden.
Major increases in treatment uptake rates are required to impact the growing burden of disease from HCV complications including cirrhosis and hepatocellular carcinoma. However, it is not clear whether HCV treatment uptake increased since the availability of BOC and TVR. We surveyed prescription activity in the USA after the FDA approval of BOC and TVR, using proprietary databases (see online methods).
The impact of these medications on the total number of HCV patients treated was small (Table 1). Over 80,000 patients were treated in 2008 prior to BOC/TVR introduction, slipping to just over 66,000 in 2010.
After initially brisk uptake of the agents after FDA approval of TVR and BOC, utilization plateaued and then declined (Fig. 1). Over 77,000 patients started HCV treatment in 2011, and of these ∼34,000 were also begun on TVR or BOC (i.e., after May 2011). By 2012, while a greater proportion of patients were on DAAs, the total number of patients treated had dropped to just over 64,000 (Table 1).
Thus, ironically, within the period the total annual number of patients treated for HCV declined since DAA introduction. These data suggest limited uptake of newer therapies, and raise concern about the public health impact of future treatments.
Using a previously developed Markov model, we sought to determine the potential impacts of treatment patterns on HCV-related morbidity and mortality. We assumed a sustained virological response (SVR) rate of 65% with BOC or TVR, accepting lower real-world SVR rates than those observed in clinical trials. These results project that should rates of treatment with current antiviral therapy continue, liver-related mortality from HCV in the U.S. will only reduce by 21% over the next 20 years.
The evolution of HCV therapy is a source of much optimism in addressing the increasing burden of complicated liver disease, yet barriers exist to realizing the potential. In our model, major benefits come not from the increase in SVR but improving treatment rates. An increase in SVR from 65% to 75% only gains an additional 1% improvement in liver-related mortality. In contrast, increasing rates of diagnosis and subsequently increasing the number of patients treated by 1.5-fold yields an additional 9% improvement in liver-related mortality. This suggests that the true rate-limiting step for addressing the HCV-associated cirrhosis epidemic lies not solely in more efficacious agents, but in getting more patients diagnosed and treated. Birth cohort-based HCV screening in baby-boomers offers one such attempt to address this need. As newer and better drugs are becoming available to clinicians, parallel public health efforts are needed to improve rates of diagnosis, referral, and treatment, to ensure that the full potential of new HCV therapies can be realized.
Paul J. Clark, M.D.
Alexander J. Thompson, M.D.
Keyur Patel, M.D.
Andrew J. Muir, M.D.
Michael L. Volk, M.D.
Duke Clinical Research Institute Duke University Medical Center Durham, NC