New and Noteworthy
- Two new Hep C medications added to Quebec provincial formulary
- Severe liver injury and liver failure common in a large sample of people with Hep C
- Adding ribavirin to Harvoni increased side effects but not cure rates
Two new Hep C medications added to Quebec provincial formulary
Harvoni and Holkira Pak have been added to the provincial formulary in Quebec for people with genotype 1 virus.
Holkira Pak is a combination of three direct-acting antivirals (DAAs). DAAs attack the ability of the Hep C virus to make copies of itself. Holkira Pak consists of:
- paritaprevir, a protease inhibitor, which is boosted with ritonavir
- ombitasvir, an NS5A inhibitor
- dasabuvir, an NS5B inhibitor
Paritaprevir/ritonavir and ombitasvir are co-formulated into one tablet. Dasabuvir is its own tablet. Holkira Pak may also be taken with ribavirin.
In clinical trials of Holkira Pak, the cure rates ranged from 90% to 100%.
For more information on Holkira Pak, see the Holkira Pak factsheet and TreatmentUpdate 207.
Harvoni is a combination of two DAAs, ledipasvir and sofosbuvir that are co-formulated into one tablet.
In clinical trials of Harvoni, cure rates ranged from 93% to 99%.
For more information on Harvoni, see the Harvoni factsheet and TreatmentUpdate 208.
Severe liver injury and liver failure common in a large sample of people with Hep C
More than one-quarter of people with Hep C who receive care through a large U.S. health maintenance organization developed severe liver injury (cirrhosis) over 12 years, which is higher than expected, reported researchers at Digestive Diseases Week 2015 in Washington, DC.
The 24,968 participants with Hep C were drawn from Kaiser Permanente (KP) Southern California, a U.S. organization that provides healthcare to its members. The majority of participants were men (60%) and the average age was 53 years.
This was a retrospective study, which means it looked backwards in time (between 2002 and 2013) to analyze outcomes in people with Hep C.
At the beginning of the study period, 19% of participants had severe liver injury or cirrhosis and 81% did not have cirrhosis.
Of the patients without cirrhosis, 23% received a new diagnosis of cirrhosis over the study period. This translated to an annual rate of 5.63%.
Of the people with cirrhosis, 40% developed liver failure or decompensation over the study period. This translated to an annual rate of almost 10%.
People in both groups who experienced progressive liver injury tended to have additional major health issues, such as cardiovascular disease and diabetes.
“Our study lends support for early diagnosis and treatment of chronic hepatitis C to reduce morbidity and mortality,” they concluded. (HIVandhepatitis.com, July 2015, in English)
Adding ribavirin to Harvoni increased side effects but not cure rates
Combining Harvoni with ribavirin increased side effects but did not increase the cure rates according to an analysis of late-stage clinical trial data published in Hepatology.
Harvoni is a combination of two medications, ledipasvir and sofosbuvir, which are combined together into one pill.
This study looked at three late-stage clinical trials testing Harvoni with or without ribavirin in people with genotype 1:
- 865 people who had never been treated before (16% with severe liver injury or cirrhosis), were treated for 12 or 24 weeks
- 440 people who had been treated before but didn’t respond to treatment (20% with cirrhosis) were treated for 12 or 24 weeks
- 647 people who had never been treated before (no one with cirrhosis) were treated for eight or 12 weeks
The overall cure rate was 97% – both for people who received ribavirin and those who didn’t.
The people in the treatment arms that included ribavirin experienced more side effects (71%) than the treatment arms that didn’t (45%).
Reported side effects included fatigue, insomnia, irritability, rash and itchy skin.
“[Sofosbuvir/ledipasvir] plus ribavirin was associated with a greater incidence of adverse events as well as concomitant medication use than [sofosbuvir/ledipasvir] alone,” the study authors concluded. “Use of ribavirin did not impact the efficacy of [sofosbuvir/ledipasvir] regimens in the ION Phase III studies.”
While the overall cure rates with and without ribavirin were the same in these studies, the majority of participants had not been treated before and did not have cirrhosis- situations where Hep C is generally considered easier to treat. Ribavirin may still have a role to play in treating the most challenging patients. (HIVandhepatitis.com, June 2015, in English)