May 12, 2014
By David Douglas
NEW YORK - In well-compensated cirrhotic patients with HCV-1, peginterferon/ribavirin along with boceprevir appears to have a generally favorable benefit-risk profile, according to pooled data from phase 3 studies.
In an April 17th online paper in the Journal of Hepatology, Dr. John Vierling of Baylor College of Medicine, Houston, Texas and colleagues note that HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials.
Moreover, as Dr. Vierling told Reuters Health by email, "many areas of the world will continue to use combination boceprevir plus peginterferon and ribavirin (PR) for treatment of HCV genotype 1 patients due to cost considerations with newer all oral options."
He added, "The high rates of serious adverse events, deaths and decompensations requiring liver transplantation in the French CUPIC study of open label use of either boceprevir + PR or telaprevir + PR in 'compensated' cirrhotic patients with HCV genotype 1 infections prompted us to perform the meta-analysis."
His team pooled data from five phase 3 trials of boceprevir + PR, focusing on the cirrhotic patients.
The patients received peginterferon and ribavirin for four weeks and continued on that regimen or had boceprevir added to their therapy, which lasted from 24 to 44 weeks.
Overall, in the 212 cirrhotic patients (Metavir fibrosis stage 4), the pooled meta-estimate for sustained virologic response (SVR) was 55% with boceprevir and 17% without. In F3 patients, estimated SVR with boceprevir was similar (54%).
In addition, say the investigators, "the SVR rates were particularly high (89%) in F4 patients who were HCV-RNA undetectable at treatment week 8; these patients accounted for 43% of the total treated cirrhotic population."
Furthermore, F3 and F4 patients with undetectable viral load at treatment week 8 achieved similar SVR rates with durations of treatment between 28 and 40 weeks compared to 40 weeks or more.
Predictors of SVR in F3 and F4 patients included male gender, low baseline viral load, and viral responses at weeks 4 and 8.
Anemia and diarrhea occurred more frequently in cirrhotic than non-cirrhotic patients - and more often with boceprevir. The proportion of serious adverse events was also higher in F4 patients treated with the boceprevir combination than in f0 to F2 or F3 patients (18% vs 12%).
The researchers point out that one limitation of the meta-analysis is that the five trials enrolled stable, well-compensated cirrhotics who may differ from cirrhotic patients in clinical practice.
Also, they say, although the treatment can help achieve SVR, "the frequency of serious adverse events, transfusions, anemia and thrombocytopenia (grade 4) were higher in F4 patients treated with boceprevir + PR compared to F0-F2 patients. Therefore, our results demonstrate both the potential benefits and risks of treating F4 patients."
Summing up, Dr. Vierling added, "Our results indicated that treatment of patients with compensated biopsy-proven cirrhosis had a favorable benefit-risk profile and that boceprevir + PR was safe and effective in this population of patients. The most significant predictor of SVR was undetectable HCV RNA at week 8."
In fact, he continued, "patients who had undetectable HCV RNA at week 8 could achieve SVR if the total treatment duration was greater than 28 weeks. Thus, the HCV RNA at treatment week 8 is informative for decisions about continuing or shortening therapy based on individual patient needs and characteristics."
J Hepatol 2014.
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