By Michael Smith, North American Correspondent, MedPage Today
Published: April 29, 2013
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania
AMSTERDAM – Three-drug therapy appears to help liver transplant patients whose hepatitis C (HCV) recurs, a researcher said here.
In early results from an observational cohort, about two-thirds of evaluable patients had undetectable virus 4 weeks after the end of therapy with pegylated interferon and ribavirin along with a protease inhibitor, according to Elizabeth Verna, MD, of Columbia University in New York City.
But that must be "balanced" against a high rate of adverse events, including need for hospital admission, kidney dysfunction, and death, Verna reported at the meeting of the European Association for the Study of the Liver.
Treatment with pegylated interferon and ribavirin has been shown to lead to sustained virologic responses in about 30% of patients with the hard-to-treat genotype 1 of the virus, Verna noted.
And adding one of the recently approved protease inhibitors – telaprevir (Incivek) or boceprevir (Victrelis) – improves the odds, she said.
But triple therapy has not been tested in transplant patients whose genotype 1 virus recurs, usually in a very aggressive fashion. To help fill the gap, she and colleagues are following 112 patients receiving triple therapy at six U.S. centers.
Of those, she noted, 15 had been on pegylated interferon and ribavirin for more than 90 days before the protease inhibitors were approved in mid-2011 and they could be started on the new drugs.
Those patients were excluded from efficacy analyses, but included in safety studies.
The other 97 patients had a short lead-in period with interferon and ribavirin, followed by triple therapy (with telaprevir in most cases), and then took interferon and ribavirin again, for a total of 48 weeks.
Verna presented efficacy data at the EASL meeting on a subset of 43 patients who have completed therapy and had at least 4 weeks of observation afterward. Most remaining patients are still on interferon/ribavirin.
Verna said that 63% of those patients had what she called an extended rapid virologic response, defined as undetectable HCV viremia 4 and 12 weeks after the start of triple therapy.
At the end of therapy, 67% had undetectable viremia, and 4 weeks later the rate was 65%.
Currently, in the era of triple therapy and a host of investigational direct-acting HCV drugs, undetectable viremia 12 weeks after the end of therapy is regarded as tantamount to a cure.
While the early efficacy results are promising, Verna said 11% of the cohort had adverse events that led to stopping treatment, 21% needed to be admitted to hospital, 34% needed transfusions, 4% suffered graft rejection, and 6% died (4% from liver-related causes).
The study is an important step forward, although the results remain preliminary, commented Patrizia Burra, MD, PhD, of Padova University Hospital in Padua, Italy, who was not involved in the study but who moderated an EASL session at which it was presented.
At a minimum, the investigators have "demonstrated that [triple therapy] can be used quite safely," she told MedPage Today. She noted that high rates of adverse events are to be expected in these patients, many of whom have aggressive disease.
Also the preliminary efficacy data are encouraging, she said, and suggest it may be possible to rescue HCV patients who relapse after transplant. "We're really hoping to see good results," she said.
Neither Verna nor Burra reported any conflicts of interest.
Primary source: European Association for the Study of the Liver
Source reference:
Verna EC, et al "A multicenter study of protease inhibitor-triple therapy in hcv-infected liver transplant recipients: Report from the CRUSH-C group" EASL 2013; Abstract 23.
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