Oral Combo Tx Soars in HCV
In one large international study, 99.3% of patients infected with genotype 1b receiving ABT-450/r plus ombitasvir and dasabuvir -- the direct-acting 3D regimen -- without ribavirin showed sustained virologic responses at 12 weeks (SVR12), as did 98.7% of those who were given that regimen plus ribavirin, Andreas Maieron, MD, of Elisabeth Hospital in Linz, Austria, reported during the presidential plenary session at the annual meeting of the American College of Gastroenterology.
Published: Oct 20, 2014
PHILADELPHIA -- Oral combination therapy for hepatitis C virus (HCV) infection continues to have striking efficacy, even without additional ribavirin and also in patients with cirrhosis, studies presented here found.
Action Points
- Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Oral combination therapy for hepatitis C virus infection continues to have striking efficacy, even without additional ribavirin and also in patients with cirrhosis, according to results from an international study.
- Note that in another study of patients with Child-Pugh A cirrhosis treated with of ABT-450/r/ombitasvir, dasabuvir, plus ribavirin, not only were high rates of sustained virologic response achieved, but liver enzymes normalized in the majority of patients during treatment.
In addition, unlike a previous study that compared treatment outcomes using this regimen with or without ribavirin, the 599 patients in this trial could have been previously treated with pegylated interferon/ribavirin. The patients in this study did not have cirrhosis.
In a second study, 3D plus ribavirin was evaluated in patients with Child-Pugh A cirrhosis.
'Optimal Treatment Efficacy'
ABT-450/r is an NS3/4A protease inhibitor dosed with ribavirin. Ombitasvir is an NS5A inhibitor, and dasabuvir is a non-nucleoside NS53 RNA polymerase inhibitor. ABT-450/r/ombitasvir was given in doses of 150 mg/100 mg/25 mg once daily, and 250 mg of dasabuvir was given twice daily.
Only one patient (in the 3D plus ribavirin group) experienced virologic breakthrough, at week 10, and none relapsed. Two patients in the 3D group were classified as not achieving SVR12 because their week 12 post-treatment follow-up was missing. In the 3D-ribavirin group, two had discontinued because of adverse events and one missed the 12-week follow-up.
Serious adverse events were reported in 0.7% of those in the 3D plus ribavirin group and in 1% of the 3D group. However, there was more nausea and pruritus in the ribavirin group, and more instances of grade 3 elevations in bilirubin, although these were transient, Maieron said.
"Both regimens were well tolerated, as evidenced by the low rates of serious [adverse events], and in the absence of interferon, ribavirin was well tolerated and was associated with low rates of anemia," he said.
There were no differences between the two groups in SVR12 when outcomes were analyzed according to multiple baseline factors. For instance, among those who were treatment naive, SVR12 rates were 99% in the 3D group and 99.5 in the 3D/ribavirin group, while for those with previous treatment, the rates were 100% and 96.6%.
Among blacks, rates of SVR12 were 100% for both regimens, and among women, rates were 100% for 3D and 98.7% for 3D plus ribavirin.
For those whose body mass index (BMI) was 30 kg/m2 or higher, the rates were 96.9% and 97.8%, and for those 65 and older, the rates were 100% in both groups.
For the IL28B non-CC genotype, the rates were 99.6% and 98.4%, while for fibrosis stage F3, rates were 93.9% and 97.1%.
"These regimens provided optimal treatment efficacy regardless of previous treatment response, and regardless of demographics or baseline characteristics," Maieron concluded.
'Hepatic Improvements'
In the next study presented in the plenary session, 3D plus ribavirin was evaluated for patients with Child-Pugh A cirrhosis. In this presentation, not only were high rates of SVR achieved, but liver enzymes normalized in the majority of patients during treatment, reported Gregory Everson, MD, of the University of Colorado in Aurora.
"The previous talk was focused on virologic response, but this talk is actually focused on hepatic improvements," Everson said.
"In the era of interferon, we all noticed that patients with advanced fibrosis and cirrhosis experienced improvements in long-term follow-up when they achieved sustained virologic response, including important clinical endpoints -- reduction in liver-related death, all-cause mortality, hepatocellular carcinoma, and reduced risk of liver decompensation and need for transplantation," he said.
"So that was all great, but interferon wasn't well tolerated in this population, and rates of sustained virologic response were low. But now we have interferon-free treatments that target the virus at multiple levels and hopefully we can have a greater impact on this condition in a larger number of patients," he said.
The current data represent an analysis of a phase III trial in an exclusively cirrhotic population of patients infected with genotypes 1a or 1b.
The same 3D regimen was used as in the previous study, combining ABT-450/r/ombitasvir and dasabuvir, along with weight-based ribavirin.
Patients were eligible for the study if they had platelet counts at or above 60,000 cells/mm3, serum albumin of 2.8 g/dL or more, and total bilirubin below 3 mg/dL. These patients were sicker than those who have been reported in much of the literature on antiviral therapy for cirrhosis, Everson pointed out.
Among 380 patients randomized to receive the 3D plus ribavirin for 12 or 24 weeks, SVRs were seen in 92% and 96%, respectively.
In a virtual press conference, John R. Saltzman, MD, of Brigham and Women's Hospital in Boston and chair of the ACG's education affairs committee, said that the results "showed an impressive response rate, and more surprising than the response rate in the 90+ range was that some of the liver parameters actually improved."
"The results were really quite spectacular," Everson agreed. "We assessed the impact on liver injury with liver enzymes, the impact on liver function with changes in bilirubin, albumin, and prothrombin time, and the impact of treatment on portal hypertension using platelet count as a surrogate," he said.
The study population was predominantly white males, age 57, with a mean BMI of 28 kg/m2.
In patients treated for both 12 weeks and 24 weeks, among those with baseline elevations of liver enzymes, normalization occurred by the end of treatment in the majority. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had normalized by the end of treatment in 93.1% and 87.8%, respectively. Gamma-glutamyl transpeptidase normalized in 92.5%.
In the group treated for 12 weeks, ALT was 99 U/L at baseline, falling to 24 U/L at the end of treatment, while AST decreased from 88 U/L to 27 U/L.
And among patients treated for 24 weeks, ALT decreased from 100 U/L to 19 U/L, while AST declined from 92 U/L to 24 U/L.
Among patients who had abnormalities in conjugated bilirubin prior to treatment, 90% normalized with treatment, while among those who had albumin abnormalities, 80% to 90% normalized post-treatment, even though the mean change was modest, he said.
A trend also was seen for change in prothrombin time at week 12, with 60% of those with abnormalities at baseline showing normalization.
Platelet counts increased in both groups and were significantly changed in the 24-week group, with 20% showing normalization.
There were no laboratory signs of decompensation during the trial, he said.
"So in summary, this treatment of 3D with ribavirin improved liver injury, as measured by normalization of enzymes, benefited liver function as shown by normalization of bilirubin and albumin, and had a trend toward an increase in platelet numbers, which may be a surrogate for portal hypertension," Everson said.
"So we would conclude that this 3D plus ribavirin treatment in patients with cirrhosis led to early improvement in measurements of hepatic injury and liver function, but longer follow-up may be required to establish the platelet count as a surrogate for portal hypertension," he said.
The study by Maieron's group was supported by AbbVie. Maieron disclosed relevant relationships with MSD, Janssen Therapeutics, AbbVie, Boehringer Ingelheim, Gilead Sciences, BMS, Rottapharm-Madaus, and Roche. Some co-authors disclosed relevant relationships with MSD, Janssen, AbbVie, Boehringer Ingelheim, Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK), Roche, Gilead Sciences, Merz, and Merck. The study by Everson's group was supported by AbbVie. Everson disclosed relevant relationships with AbbVie, Vertex, BMS, Merck, Roche/Genentech, Gilead/Pharmasset, GSK, Novartis, Tibotec, Janssen, Novartis, Eisai, Biotest, and HepQuant. Some co-authors disclosed relevant relationships with AbbVie, BMS, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, Vertex, Achillion, Idenix, Novartis, Santaris, Janssen Cilag, Sanofi, and Tibotec.
Source - MedPage Today
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