Adverse Events Common With Triple Therapy in HCV Cirrhosis

May 22, 2013

By David Douglas

NEW YORK (Reuters Health) May 22 - In cirrhotic patients, triple-therapy against hepatitis C virus (HCV) produces a high virological response rate, but at the cost of a high rate of serious adverse events, French researchers say.

In the French CUPIC cohort, four in ten cirrhotic patients on triple therapy with pegylated interferon and ribavirin plus boceprevir or telaprevir suffered a serious complication (death, severe infection, or hepatic decompensation).

This cohort, Dr. Christophe Hézode told Reuters Health by email, consisted of "HCV genotype 1 treatment-experienced patients with compensated cirrhosis."

In a May 13th online paper in The Journal of Hepatology, Dr. Hézode of Universite Paris-Est, Creteil and colleagues say phase III trials have yielded similar results in treatment-experienced cirrhotics and non-cirrhotics, but patients were highly selected.

To evaluate the effect in "real-world" patients, the team analyzed 497 patients who reached at least week 16 in a 48-week triple therapy early access program. All had previously received interferon.

Forty percent (199 patients) had serious adverse events, with 58 patients stopping their treatment as a result. Refractory anemia was also common. Six patients died and another 32 (6.4%) had severe infection or hepatic decompensation or another serious event.

Death or severe complications were related to platelet counts at or below 100,000/mm3 (odds ratio 3.11) and albumin <35 g/dL (OR 6.33).

In patients with both of these risk factors, who accounted for 7.9% of the cohort, the rate of severe complications was 44.1%, "suggesting that they should not be treated with the triple therapy." In the remaining 92.1%, the risk was at or below 7.1%.

In an intention-to-treat analysis in the 292 patients treated with the telaprevir combination, HCV RNA was undetectable in 78.8% at week 12 and 67.1% at week 16. In the 205 given boceprevir, the corresponding proportions were 54.6% and 58.0%.

Although the safety profile of triple therapy is poor in a real-life setting, the approach "was associated with high rates of on-treatment virological response," the authors report.

Overall, they say "Serum albumin level and platelet count should be evaluated to determine the risk/benefit ratio of triple therapy in cirrhotic patients and to decide treatment."

"Patients combining a platelet count of less 100,000 /mm3 and serum albumin below 35 g/L should not be treated with a triple combination," Dr. Hézode stressed.

"The other patients," the team concludes, "could be treated cautiously and carefully monitored."

Commenting on the findings by email, Dr. Savino Bruno of A. O. Fatebenefratelli e Oftalmico, Milan, Italy told Reuters Health that "risk overcame benefit" in a number of patients. However, "a more reliable on-treatment stopping rule... may maximize benefit and minimize risk."

Other research on the CUPIC cohort that was recently presented at the 48th annual meeting of European Association for the Study of the Liver, sheds more light on a related strategy. In that study, by investigators including Dr. Hézode found that independently of cirrhosis severity, baseline concentration of apolipoprotein H was associated with early virological response.

SOURCE: http://bit.ly/14S1CwV

J Hepatol 2013.

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