Trial Supports Addition of Telaprevir for HCV Genotype 2
BY DENISE NAPOLI
Elsevier Global Medical News Adding telaprevir to the standard regimen of peginterferon-alfa and ribavirin reduced the time needed to attain decreased viral loads in genotype 2 hepatitis C virus infection, reported Dr. GrahamR. Foster and his colleagues in the September issue of Gastroenterology.
The drug was less effective in patients with genotype 3 hepatitis C virus (HCV),in the first study to assess use of telaprevir for treating these strains. Dr. Foster,of Queen Mary University of London,and colleagues looked at treatment-naivepatients with HCV genotypes 2 and 3 (23and 26 participants, respectively).Patients received either telaprevir monotherapy (750 mg every 8 hours), telaprevir plus peginterferon alfa-2a (180mcg/week) and ribavirin (400 mg twice daily),or placebo plus peginterferon/ribavirin for 15 days, followed by the standard peginterferon/ribavirin regimen for 22 or 24weeks.
On day 8 of treatment, the proportion of patients with undetectable HCV RNA was 0% in the telaprevir monotherapy group, 20% in the telaprevirplus peginterferon/ribavirin group,and 0% in the peginterferon/ribavirin only cohort. By day 15, the proportions were 0%, 40% (2 of 5 patients), and22% (2 of 9 patients), respectively.The median times to undetectableHCV RNA were 31, 12, and 43 days in thetelaprevir monotherapy group, the telaprevir plus peginterferon/ribavirin group, and the peginterferon/ribavirin only group.
Moreover, the proportions of patients with a sustained virologic response(SVR), defined as undetectable HCV RNA at end of treatment and 24weeks after final study medication, were56% in the monotherapy cohort (5 of 9patients), 100% in the dual telaprevir plus peginterferon/ribavirin group (5 of 5 patients),and 89% in the peginterferon/ribavirin-only group (8 of 9 patients).
There was less success among patients with genotype 3 of the disease. The median times to first undetectable HCV RNA result among these patients were 99, 43,and 29 days for the monotherapy cohort,the telaprevir plus peginterferon/ribavirin group, and the peginterferon/ribavirin only group, respectively. Likewise, the corresponding SVR rates were 50% (4/8),67% (6/9), and 44% (4/9), respectively.The most frequently reported adverse events were flu like illnesses and pruritis.
Of the five reported serious adverse events,only one – pneumonia – was considered related to the study medication, in this case, peginterferon/ribavirin. Based on theefficacy shown among treatment-naive patients, “the potential of telaprevir-based triple combination therapy in patients with HCV genotype 2 who have not responded to peginterferon/ribavirin should be explored,” said the authors.And while the drug’s poor performance among genotype 3 patients makes it “unlikely to have major clinical utility in this patient sub population,… for treatment-naive patients with genotype 2 HCV, studies to examine a shortened duration of therapy that includes telaprevir should be considered.”
The study was sponsored by Janssen Pharmaceuticals and Vertex Pharmaceuticals.
Several authors had financialrelationships with multiple pharmaceuticalcompanies, including Tibotec Pharmaceuticals.
Two investigators were alsoemployees of Tibotec or Janssen. ?
Received 23 June 2011; received in revised form 26 July 2011; accepted 2 August 2011. published online 30 August 2011. Accepted Manuscript
Dermatological adverse events (AEs) are an existing concern during hepatitis C virus (HCV) infection and peginterferon/ribavirin treatment. HCV infection leads to dermatological and muco-cutaneous manifestations including small-vessel vasculitis as part of the mixed cryoglobulinemic syndrome.
Peginterferon/ribavirin treatment is associated with well-characterized dermatological AEs tending towards a uniform entity of dermatitis. New direct-acting antivirals have led to significant improvements in sustained virologic response rates, but several have led to an increase in dermatological AEs versus peginterferon/ribavirin alone.
In telaprevir trials, approximately half of treated patients had rash. More than 90% of these events were Grade 1 or 2 (mild/moderate) and in the majority (92%) of cases, progression to a more severe grade did not occur. In a small number of cases (6%), rash led to telaprevir discontinuation, whereupon symptoms commonly resolved. Dermatological AEs with telaprevir-based triple therapy were generally similar to those observed with peginterferon/ribavirin (xerosis, pruritus and eczema).
A few cases were classified as severe cutaneous adverse reaction (SCAR), also referred to as serious skin reactions, agroup of rare conditions that are potentially life-threatening. It is therefore important to distinguish between telaprevir-related dermatitis and SCAR. The telaprevir prescribing information does not require telaprevir discontinuation for Grade 1 or 2 (mild/moderate) rash, which can be treated using emollients/moisturizers and topical corticosteroids.
For Grade 3 rash, the prescribing information mandates immediate telaprevir discontinuation, with ribavirin interruption (with or without peginterferon) within 7 days of stopping telaprevir if there is no improvement, or sooner if it worsens. In case of suspicion or confirmed diagnosis of SCAR, all study medication must be discontinued.
SCAR- Severe Cutaneous Adverse Reactions Cutaneous drug reactions occur when your skin has a reaction to a drug.
DRESS-(Drug Reaction with Eosinophilia and Systemic Symptoms) Japanese Dermatologists call this syndrome DIHS (Drug Induced Hypersensitivity Syndrome) while European and American dermatologists suggested the acronym of DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)
DRESS is one of several terms that has been used to describe a severe idiosyncratic reaction to a drug that is characterized by a long latency of onset after exposure to the offending medication, a rash, involvement of internal organs, hematologic abnormalities and systemic illness.
Hepatitis C Drug Incivek (telaprevir); What are the side effects ?
Use of New HCV Protease Inhibitors ‘Not That Simple’
The most recent issue of the Journal of Viral Hepatitis investigates sex and age differences in lipid response to chronic infection with the hepatitis C virus in the United States National Health and Nutrition Examination Surveys.
Low levels of serum lipids were reported in subjects chronically infected with the hepatitis C virus (HCV) and correlated with poorer clinical outcomes.
Whether HCV ‘hypo-lipidemia’ is constant across age, sex and race has not been systematically explored.
Dr Lao and colleagues from North Carolina, USA investigated the association between HCV infection and serum lipid levels in 2 independent National Health and Nutrition Examination Survey (NHANES) cohorts.
HCV antibody status and serum lipid levels were obtained from 14,369 adults from NHANES 1999–2006 and 12,261 from NHANES III.
Among women less than 50 years of age, the odds ratio was 3 for NHANEs III
Journal of Viral Hepatitis
The research team found that the prevalence of HCV-associated hypo-low density lipoprotein-cholesterol was highest among women more than 50 years of age in both NHANES 1999–2006 and III.
However, among women less than 50 years of age, the odds ratios were 3 for NHANES 1999–2006 and 0.5 for III, respectively.
HCV by age interaction among women was significant in both cohorts.
Among men, the odds ratios of HCV-associated hypo-LDL-cholesterol were 2.7 in NHANES 1999–2006, and 3.8 in III, respectively, with no significant age effects.
The team observed similar patterns for total-cholesterol, but no significantly discernable patterns for high density lipoprotein-cholesterol and triglycerides.
Dr Lao's team commented, "Results show that HCV infection is associated with lower total- and LDL-cholesterol in 2 US population-based cohorts, and this relationship varies significantly by age and sex, suggesting a possible influence of sex hormones on host lipid response to HCV infection."
J Viral Hep 2011: 18(8): 571–579
28 July 201128 July 2011 hepatitiscnewdrugs.blogspot.com
Sustained virological response was associated with HCV genotypes 2–3
Journal of Viral Hepatitis
The most recent issue of the Journal of Viral Hepatitis investigates treatment of chronic hepatitis C in HIV-HCV coinfected patients with compensated liver cirrhosis.
The greatest benefit of hepatitis C virus (HCV) therapy is seen in cirrhotics attaining sustained virological response.
However, concerns about toxicity and poorer responses often discourage treatment of cirrhotics.
This may be particularly relevant in HIV–HCV-coinfected patients, in whom progression of liver fibrosis is faster and treatment responses lower.
Dr Luz Martin-Carbonero and colleagues from Spain performed a retrospective analysis of HIV–HCV-coinfected patients who had received peginterferon–ribavirin therapy at their institution.
Individuals naïve for interferon in whom liver fibrosis had been assessed using elastometry within the year before being treated were chosen.
Response rates and toxicities were compared in cirrhotics and noncirrhotics.
Patients with previous liver decompensation were excluded.
Overall, the team found that 41 cirrhotics and 190 noncirrhotics entered the study.
Groups were similar in age, gender, HCV genotypes and baseline serum HCV-RNA.
The research team observed that sustained virological response occurred at similar rates in cirrhotic and noncirrhotics, either considered by intention-to-treat or as treated.
The researchers found that sustained virological response was associated with HCV genotypes 2–3 and lower serum HCV-RNA but not with cirrhosis.
The team noted that treatment discontinuations because of adverse events tended to be more common in cirrhotics than in noncirrhotics, but only severe thrombocytopenia was more frequent in cirrhotics than in non-cirrhotics.
Dr Martin-Carbonero's team concluded, "Response to peginterferon–ribavirin therapy is similar in HIV–HCV coinfected patients with and without liver cirrhosis."
"Therefore, treatment must be encouraged in all compensated cirrhotic patients, although closer monitoring and management of side effects, mainly thrombocytopenia, may be warranted."
J Viral Hep 2011: 18(8): 542–548
29 July 2011 hepatitiscnewdrugs.blogspot.com
The latest issue of Alimentary Pharmacology & Therapeutics investigates epidemiology of hepatitis C genotype 6 and its management.
Hepatitis C virus (HCV) genotype 6 is common among patients from Southeast Asia and the surrounding regions, where HCV prevalence is also high.
HCV genotype 6 has great genetic diversity and different response to antiviral therapy compared with the more commonly known genotype 1.
Dr Nguyen and colleagues from California, USA provided a systematic review of the current literature on the epidemiology, classification and treatment of HCV genotype 6.
The prevalence of HCV genotype 6 is estimated to be as high as 50% in some regions
Alimentary Pharmacology & Therapeutics
A search using PubMed for ‘hepatitis C’ AND ‘genotype 6’ produced a total of 47 articles, of which 33 articles were found to be relevant and included in this review.
Additional articles were identified using the reference lists of these 33 primary articles.
The research team found that the prevalence of HCV genotype 6 is estimated to be as high as 50% in some regions of Southeast Asia with demonstrated significance among intravenous drug users, and thalassemia major patients.
Although previous line probe assays may have misclassified HCV genotype 6 as genotype 1, newer line probe assays can more accurately and reliably determine HCV genotype.
The team observed that patients infected with HCV genotype 6 respond better to interferon-based therapy compared with those infected with genotype 1, although patient baseline clinical characteristics and side effect profiles are similar between HCV genotype 6 and other HCV genotypes.
Dr Nguyen's team concludes, "Future studies should seek to clarify issues regarding early predictors for treatment response in patients with HCV genotype 6, and the impact of ethnic and genotypic factors to treatment response in HCV genotype 6 patients."
Aliment Pharmacol Ther 2011; 34: 286–296
14 July 2011 hepatitiscnewdrugs.blogspot.com
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