Ever improving treatment tolerability
Care for Hepatitis C in the early 1990s consisted of daily interferon injections, which had debilitating side effects and a very low cure rate. Once clinicians began adding ribavirin to the mix, cure rates rose to 25 percent, but the toxicity of the daily interferon was difficult to manage, and treatment duration was 48 weeks. Pegylated interferon, which could be given just once a week, improved treatment tolerance greatly, but only raised cure rates to about 40 percent. In 2009, the introduction of two protease inhibitors — telaprevir and boceprevir — brought cure rates to 60 percent, but side effects worsened.
Late last year, "A sea change occurred," says Jeff McKinney, a nurse practitioner who clinically manages all the hepatology patients on Hepatitis C treatment at Stanford. Two new medications — simeprevir and sofosbuvir — received FDA approval. These two DAAs inhibit the mechanism by which the virus replicates, and attack the virus in two different locations. With these new drugs, treatment duration plummeted to 12 weeks for most patients, side effects were greatly reduced and cure rates soared to between 80 and 97 percent depending on the patient's level of liver disease and genotype of Hepatitis C.
There are three and a half to four million people in the U.S. alone with chronic Hepatitis C. "Our goal is to identify as many of those people as we can and get them into care and treatment," says McKinney. Left untreated, Hepatitis C can cause progressive liver disease and liver cancer, and is the most common cause of liver transplantation.
"It's exciting to see patients in clinic who have been living with this disease for decades and we're now curing their disease," says McKinney.
Lutchman and McKinney are now looking ahead to FDA approval of an all-oral treatment regimen later this year, which would eliminate the need for injectable interferon completely, and reduce the treatment duration even further. Both clinicians say the research pipeline for new medications is rich, and the "Holy Grail" of Hepatitis C treatment may soon become available — one tablet, once a day, for the most common for of Hepatitis C.
The Stanford protocol
Stanford has treated more than 200 patients with chronic Hepatitis C so far using directly acting antiviral agents. "We looked at the published data on all the different drug regimens, the different subtypes of patients and the different subtypes of virus, and created a treatment algorithm for each type," says Lutchman.
For patients who cannot tolerate interferon, Stanford uses an off-label treatment that is in the guidelines of the American Association of Liver Disease, says Lutchman. In this all-oral protocol, patients take sofosbuvir with simeprevir once a day for 12 weeks, and the cure rate is more than 90 percent. Because this regimen is not FDA approved, it can be difficult to get insurance coverage, and it is expensive – 12 weeks of sofosbuvir costs $84,000, and simeprevir is an additional $70,000.
McKinney works with insurance companies to gain approval for treatment by appealing denials, writing letters and providing proof of necessity. In the few cases when coverage is denied, patients have one of two options. If they have very mild liver disease, they are encouraged to wait for FDA approval of newer all-oral regimens. If they cannot wait to begin treatment, McKinney applies directly to the pharmaceutical companies' patient assistance programs.
Stanford has had success treating patients with all types of Hepatitis C, including those who are healthy otherwise, as well as patients with liver failure, de-compensated liver disease and disease recurrence post liver transplant. The benefits to treating patients on the transplant list are enormous, says Lutchman. "If you cure the Hepatitis C, there is data to suggest that some patients may not need a transplant. That's not a paradigm that has ever existed for Hepatitis C liver disease before." The all-oral regimen has also made treatment post transplant a possibility, he adds. In the past, it was difficult to use interferon with transplant patients because it could cause organ rejection. With the new DAAs, there's no added risk of rejection, and there are no significant interactions with post-transplant medications.
To refer a patient for an evaluation for Hepatitis C treatment, please contact the Stanford Health Care referral center at 866-742-4811.
By Grace Hammerstrom