Reviewer's report
Title:Safety and efficacy of protease inhibitor based combination therapy in a
single-center "real-life" cohort of 110 hepatitis C genotype 1 patients
Version:2Date:21 January 2014
Reviewer: Martin-Walter Welker
Reviewer's report:
In the current work, Wehmeyer et al investigated efficacy and safety of telaprevir
(n= 65) or boceprevir (n=37) based antiviral therapy in patients with chronic
hepatitis C treated without pivotal trials. Of note, 64% of the patients included
met exclusion criteria of pivotal trials. The authors found that the overall SVR rate
was comparable to those reported from pivotal trials. Moreover they performed a
safety analysis. The aim of the work is interesting in principle; since telaprevir or
boceprevir based antiviral therapy may be used in some regions in the coming
years despite the recently approved DAA’s. Nevertheless, some major points
have to be discussed.
Major Compulsory Revisions
First, the authors performed a retrospective analysis. This limits the conclusions
to be drawn from the results of the study. Second, although 65% of patients met
pivotal trial exclusion criteria, a fair proportion of patients would have been
excluded from pivotal trials rather due to HCC than impaired liver function. The
latter, however, was investigated by other groups previously (Maasoumy B et al.
PLoS ONE 8(2):e55285.doi:10.1371; Hézode C, et al. J Hepatol
2013;59:434-441.). In comparison with these trials, the current study provides at
least only little significant new findings. Third, the SVR 12 data of all patients
included should be provided. (“In addition, 4 patients (3.9%) completed treatment
without virological failure, but are short of 12 weeks after end of treatment (EOT)
and were excluded from the analysis regarding frequency and predictors for
SVR12.”)
Minor Essential Revisions
The Patients and Methods section should be restructured using subheadings. In
the current form, e.g., treatment of patients and laboratory methods are mixed.
Discussion section, “Therefore, treatment individualization seems to be a valid
option in difficult-to-treat patients to manage side-effects and to achieve a
reasonable chance for SVR. Out data indicate, that triple therapy seems to be a
reasonable option for DAA-experienced patients, too. This is an important
finding, since the number of DAA-experienced patients will rapidly increase in the
future.” - This conclusion cannot be drawn from a retrospective analysis. The
authors should discuss this more balanced.
Discussion section, “As a consequence of the treatment complexity of triple
therapy with increased risk for relevant and potentially lethal side-effects, the
possibility to create PI resistance and to give every patient chance to participate
in clinical trials, we significantly remodeled procedures at our clinics. Every
patient is discussed in a multidisciplinary hepatitis board before HCV triple
therapy is initiated. Additionally, every cirrhotic patient is seen by the 12
transplant team before treatment initiation and listed for liver transplantation if
deemed necessary.” - This is reasonable, but cannot be based on the data of this
study. The paragraph should be deleted.
The manuscript should be carefully revised with respect to typos and grammar
(e.g. Abstract, “Combination”).
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Safety and efficacy of protease inhibitor based combination therapy in a
single-center "real-life" cohort of 110 hepatitis C genotype 1 patients
Version:2Date:21 January 2014
Reviewer: Martin-Walter Welker
Reviewer's report:
In the current work, Wehmeyer et al investigated efficacy and safety of telaprevir
(n= 65) or boceprevir (n=37) based antiviral therapy in patients with chronic
hepatitis C treated without pivotal trials. Of note, 64% of the patients included
met exclusion criteria of pivotal trials. The authors found that the overall SVR rate
was comparable to those reported from pivotal trials. Moreover they performed a
safety analysis. The aim of the work is interesting in principle; since telaprevir or
boceprevir based antiviral therapy may be used in some regions in the coming
years despite the recently approved DAA’s. Nevertheless, some major points
have to be discussed.
Major Compulsory Revisions
First, the authors performed a retrospective analysis. This limits the conclusions
to be drawn from the results of the study. Second, although 65% of patients met
pivotal trial exclusion criteria, a fair proportion of patients would have been
excluded from pivotal trials rather due to HCC than impaired liver function. The
latter, however, was investigated by other groups previously (Maasoumy B et al.
PLoS ONE 8(2):e55285.doi:10.1371; Hézode C, et al. J Hepatol
2013;59:434-441.). In comparison with these trials, the current study provides at
least only little significant new findings. Third, the SVR 12 data of all patients
included should be provided. (“In addition, 4 patients (3.9%) completed treatment
without virological failure, but are short of 12 weeks after end of treatment (EOT)
and were excluded from the analysis regarding frequency and predictors for
SVR12.”)
Minor Essential Revisions
The Patients and Methods section should be restructured using subheadings. In
the current form, e.g., treatment of patients and laboratory methods are mixed.
Discussion section, “Therefore, treatment individualization seems to be a valid
option in difficult-to-treat patients to manage side-effects and to achieve a
reasonable chance for SVR. Out data indicate, that triple therapy seems to be a
reasonable option for DAA-experienced patients, too. This is an important
finding, since the number of DAA-experienced patients will rapidly increase in the
future.” - This conclusion cannot be drawn from a retrospective analysis. The
authors should discuss this more balanced.
Discussion section, “As a consequence of the treatment complexity of triple
therapy with increased risk for relevant and potentially lethal side-effects, the
possibility to create PI resistance and to give every patient chance to participate
in clinical trials, we significantly remodeled procedures at our clinics. Every
patient is discussed in a multidisciplinary hepatitis board before HCV triple
therapy is initiated. Additionally, every cirrhotic patient is seen by the 12
transplant team before treatment initiation and listed for liver transplantation if
deemed necessary.” - This is reasonable, but cannot be based on the data of this
study. The paragraph should be deleted.
The manuscript should be carefully revised with respect to typos and grammar
(e.g. Abstract, “Combination”).
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Safety and efficacy of protease inhibitor based combination therapy in a
single-center "real-life" cohort of 110 hepatitis C genotype 1 patients
Version:2Date:21 January 2014
Reviewer: Martin-Walter Welker
Reviewer's report:
In the current work, Wehmeyer et al investigated efficacy and safety of telaprevir
(n= 65) or boceprevir (n=37) based antiviral therapy in patients with chronic
hepatitis C treated without pivotal trials. Of note, 64% of the patients included
met exclusion criteria of pivotal trials. The authors found that the overall SVR rate
was comparable to those reported from pivotal trials. Moreover they performed a
safety analysis. The aim of the work is interesting in principle; since telaprevir or
boceprevir based antiviral therapy may be used in some regions in the coming
years despite the recently approved DAA’s. Nevertheless, some major points
have to be discussed.
Major Compulsory Revisions
First, the authors performed a retrospective analysis. This limits the conclusions
to be drawn from the results of the study. Second, although 65% of patients met
pivotal trial exclusion criteria, a fair proportion of patients would have been
excluded from pivotal trials rather due to HCC than impaired liver function. The
latter, however, was investigated by other groups previously (Maasoumy B et al.
PLoS ONE 8(2):e55285.doi:10.1371; Hézode C, et al. J Hepatol
2013;59:434-441.). In comparison with these trials, the current study provides at
least only little significant new findings. Third, the SVR 12 data of all patients
included should be provided. (“In addition, 4 patients (3.9%) completed treatment
without virological failure, but are short of 12 weeks after end of treatment (EOT)
and were excluded from the analysis regarding frequency and predictors for
SVR12.”)
Minor Essential Revisions
The Patients and Methods section should be restructured using subheadings. In
the current form, e.g., treatment of patients and laboratory methods are mixed.
Discussion section, “Therefore, treatment individualization seems to be a valid
option in difficult-to-treat patients to manage side-effects and to achieve a
reasonable chance for SVR. Out data indicate, that triple therapy seems to be a
reasonable option for DAA-experienced patients, too. This is an important
finding, since the number of DAA-experienced patients will rapidly increase in the
future.” - This conclusion cannot be drawn from a retrospective analysis. The
authors should discuss this more balanced.
Discussion section, “As a consequence of the treatment complexity of triple
therapy with increased risk for relevant and potentially lethal side-effects, the
possibility to create PI resistance and to give every patient chance to participate
in clinical trials, we significantly remodeled procedures at our clinics. Every
patient is discussed in a multidisciplinary hepatitis board before HCV triple
therapy is initiated. Additionally, every cirrhotic patient is seen by the 12
transplant team before treatment initiation and listed for liver transplantation if
deemed necessary.” - This is reasonable, but cannot be based on the data of this
study. The paragraph should be deleted.
The manuscript should be carefully revised with respect to typos and grammar
(e.g. Abstract, “Combination”).
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
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