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Review confirms DAAs effective
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A recent analysis of available literature showed that FDA–approved oral direct-acting agents, or DAAs, were associated with high rates of safety, tolerability and efficacy for the treatment hepatitis C virus infection, especially in patient populations considered difficult to treat.
“Cure of this infection, defined as the absence of detectable HCV RNA in the blood at least 12 weeks after treatment completion (sustained virologic response [SVR]), is strongly associated with reduced liver-related morbidity and mortality,” Oluwaseun Falade-Nwulia, MBBS, MPH, assistant professor of medicine at Johns Hopkins University School of Medicine, and colleagues wrote. “The development of drugs that directly inhibit key steps in viral replication had led to availability of several oral HCV treatment regimens.”
Researchers systematically reviewed data from 42 published clinical trials of adults with chronic HCV infection that assessed at least 8 weeks of an interferon-free HCV regimen and included at least two FDA–approved DAAs. These included:
- NS3 protease inhibitors, such as grazoprevir, paritaprevir and Olysio (simeprevir, Janssen Therapeutics);
- NS5A inhibitors, such as Daklinza (daclatasvir, Bristol-Myers Squibb), elbasvir, ledipasvir, ombitasvir and velpatasvir; and
- NS5B polymerase inhibitors, such as Sovaldi (sofosbuvir, Gilead Sciences) and dasabuvir.
The researchers also evaluated the effect of the oral antiviral ribavirin on rates of SVR and adverse events.
The results showed that six DAA regimens produced SVR rates of more than 95% in patients with HVC genotype 1 without cirrhosis, including those coinfected with HIV. Patients with other HCV genotypes showed similar cure rates, though effective treatments for HCV genotype 3 infection are limited, findings suggested. The researchers observed that patients with hepatic decompensation, especially those with Child-Turcotte-Pugh class C disease, experienced lower SVR rates (78% to 87%) than other patient populations.
When the researchers reviewed the addition of ribavirin, they saw more mild or moderate adverse events compared with regimens that did not contain the antiviral, and that the drug was linked with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were less than 10% across all patient populations.
“Oral DAA regimens that are highly efficacious, well-tolerated and relatively short in duration are now available for all HCV genotypes and for patient populations historically considered difficult to cure,” Falade-Nwulia and colleagues wrote. “The ease of dosing, safety profile and effectiveness of these agents provide an opportunity to expand the number of patients who can be treated for HCV infection and the pool of treating providers.”
In an accompanying editorial, Jay H. Hoofnagle, MD, and Averell H. Sherker, MD, from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, cautioned that although these findings offer a possible solution to HCV infection, challenges still remain, including access to care and the potential for significant adverse events in some patients. The authors recommended that continued follow-up remain a priority for patients with HCV infection and cirrhosis or advanced fibrosis.
“The optimal means of surveillance and the appropriate intervals and duration of monitoring are currently not clear,” they wrote. – by Savannah Demko
- References:
- Falade-Nwulia O, et al. Ann Intern Med. 2017;doi:10.7326/M16-2575.
- Hoofnagle JH, Sherker AH. Ann Intern Med. 2017;doi:19.7326/M17-0567.
Disclosures: Falade-Nwulia reports no relevant financial disclosures. Please see the full study for a complete list of all other authors’ relevant financial disclosures. Hoofnagle and Sherker report no relevant financial disclosures.