- Category: HCV Treatment
- Published on Friday, 25 April 2014 00:00
- Written by Liz Highleyman
Most people with chronic hepatitis C in the Kaiser Southern California health plan have not received treatment, often due to co-existing conditions and contraindications, but practice is evolving with the approval of more effective and better tolerated direct-acting antivirals, according to a study presented at the 49thEASL International Liver Congress this month in London.
Because interferon-based therapy caused numerous side effects, took a long time (24 to 48 weeks), and cured only about half of treated patients, hepatitis C treatment was recommended only for people with moderate or worse liver disease, as determined by liver biopsies or non-invasive tests. With new interferon-free direct-acting antivirals that are well-tolerated and can cure upwards of 90% of patients in as little as 8-12 weeks, there is shift toward thinking that more people should be eligible for treatment, but the high cost of the new drugs may limit access.
Lisa Nyberg from Kaiser Permanente in San Diego and colleagues performed an comparison of characteristics of Kaiser Permanente members treated or not treated for hepatitis C using pegylated interferon plus ribavirin or triple therapy adding boceprevir (Victrelis) or telaprevir (Incivek or Incivo). The study did not look at next-generation direct-acting antivirals, the first of which -- sofosbuvir (Sovaldi) and simeprevir (Olysio) -- were just approved in late 2013.
This retrospective cohort study included more than 50,000 adult hepatitis C patients enrolled in Kaiser Permanente Southern California, a large (3.5-4.0 million members) non-profit integrated health maintenance organization that employs medical providers, dispenses prescription medication, and handles payment as a single entity.
The analysis focused on 32,283 participants (about 60% men) who had been members for at least 6 continuous months between January 2002 and December 2012 and had prescription benefits. A majority (around 60%) were age 45-65 -- the predominant age group with hepatitis C in the U.S. -- while about 27% were under 45 and 14% were older than 65. About 40% were white, 12% were Hispanic/Latino, 12% were black, 5% were Asian, and around 30% were classified as "other."
The researchers used diagnosis codes or lab test results in medical records to identify comorbid conditions that might be considered relative or absolute contraindication for interferon-based therapy, such as anemia or decompensated liver disease.
- Among 32,283 eligible plan members, 5533 (17%) received treatment and 26,745 (83%) received no treatment.
- Among all 51,984 members identified with hepatitis C, 7945 (15%) received treatment -- similar, Nyberg noted, to the 12% treated in a Veterans Administration study.
- Conditions representing absolute or relative contraindications to interferon or ribavirin were associated with not receiving treatment.
- Conditions that can predispose patients to more aggressive liver disease or faster disease progression were associated with higher likelihood of treatment.
- 16,186 participants (50%) had a least 1 significant comorbid condition.
- Within this group, 2484 (15%) were treated while 85% were not treated -- similar to the rates for Kaiser hepatitis C patients overall.
- 42% were deemed likely to be interferon ineligible or intolerant.
- Factors significantly associated with being more likely to receive treatment included:
o Age 45-65 vs >65 (odds ratio [OR] 4.566, or more than 4 times more likely);
o Age <45 vs >65 (OR 4.384);
o Liver cirrhosis (OR 4.328);
o Prior liver transplant (OR 2.903);
o Non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH) (OR 2.854);
o Depression (OR 1.541);
o HIV/HCV coinfection (OR 1.395);
o Male sex (OR 1.184).
- Factors significantly associated with not receiving treatment included:
o Anemia (OR 0.329, or more than 60% less likely);
o Advanced liver dysfunction with a MELD score >12 (OR 0.385);
o Substance abuse (OR 0.542);
o Severe lung disease (OR 0.555)
o Cardiovascular disease (OR 0.602);
o Kidney dysfunction (OR 0.659);
o Psychosis or bipolar disorder (OR 0.678);
o Autoimmune disorder (OR 0.775).
"Treatment of HCV with peginterferon-based regimens is significantly limited by numerous comorbid conditions," the investigators concluded. "Future treatment may be better tolerated and with fewer contraindications, thus increasing treatment effectiveness and thereby reducing future morbidity and mortality of liver disease."
During the discussion after her presentation, Nyberg acknowledged that some plan participants with hepatitis C may not have been considered for treatment because they had only mild liver disease. Until now, many people with hepatitis C have been "warehoused" to await new and better drugs.
Kaiser is currently "struggling like many others" about how to manage hepatitis C patients, she said. To date Kaiser has not restricted on-label use of sofosbuvir or simeprevir, and off-label -- but recommended in the latest AASLD/IDSA/IAS-USA guidelines -- use of these 2 drugs together is now being reviewed.
"The philosophy will be to treat those with more advanced fibrosis first, but others may require treatment for other reasons, including extrahepatic manifestations," she added, noting that research has shown that hepatitis C is associated with increased all-cause mortality beyond liver-related deaths, and successful treatment reduces overall mortality. "We should treat and reduce our pool of [warehoused] patients," she said.
LM Nyberg, KM Chiang, Z Li, et al. Comorbid conditions associated with decision-making regarding treating or not treating chronic hepatitis C in a large U.S. Health maintenance organization. 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract O67.