Reviewer's report
Title:Rifaximin for maintenance therapy in antibiotic-dependent pouchitis
Version: 1Date:27 December 2007
Reviewer: Darrell S Pardi
Reviewer's report:
This is a straight-forward study of rifaximin for maintenance of remission in
antibiotic-dependent pouchitis, and the manuscript is well written. I have a few
comments/questions:
Major Compulsory Revisions
1) Given that this is basically a time-to-recurrence study, it would seem that the
construction of survival curves with Kaplan-Meier analyses would be most
appropriate, rather than the proportion of subjects in remission at various points
in time.
2) The dose of rifaximin used in this study seems too low, particularly given the
unimpressive results published recently with 400 mg TID in active pouchitis
(Issacs Inflamm Bowel Dis 2007). The authors should justify the selection of this
dose, and also incorporate this newer reference into their discussion. The low
dose of rifaximin should also be acknowledged as a potential limitation of the
present study. For example, it is not clear if the 35% relapse rate by 3 months
was due to rifaximin being a suboptimal drug for these patients, or if the dose
was simply too low. The authors did attempt to analyze the maintenance dose of
rifaximin as a predictor of maintenance of remission and found it to be
non-significant, but the majority of patients in each group only got 200 mg per
day, and 73% of the relapsers discontinued medication within 2 months.
3) The choice of 3 months maintenance also needs to be justified. In other recent
studies (eg the VSL #3 studies), the duration of follow up was longer. This issue
is particularly important given the decreasing rates of maintenance that you
report after 6 and 12 months. It is not clear if these decreasing rates are due to
insufficient follow up or loss of efficacy.
Minor Essential Revisions
1) Patients routinely using NSAID were asked to stop. Was there any wash-out
period between stopping NSAIDs and inclusion in the study? This issue is
important since your group has reported that discontinuation of NSAIDs in
regular users may lead to significant improvement in PDAI.
2) Your results wold be more useful if you could provide some comparative data
(from the literature or from your own practice) on maintenance rates with other
medications (like ciprofloxacin).
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I helped develop and am participating in a study of rifaximin in C. difficile colitis.
As part of that work, I have served as a consultant to Salix (makers of rifaximin).
I have also collaborated with the first author on several pouchitis projects.
I believe I have been able to give a fair assessment of this manuscript despite
these potential conflicts.
Reviewer's report
Title:Rifaximin for maintenance therapy in antibiotic-dependent pouchitis
Version: 1Date:27 December 2007
Reviewer: Darrell S Pardi
Reviewer's report:
This is a straight-forward study of rifaximin for maintenance of remission in
antibiotic-dependent pouchitis, and the manuscript is well written. I have a few
comments/questions:
Major Compulsory Revisions
1) Given that this is basically a time-to-recurrence study, it would seem that the
construction of survival curves with Kaplan-Meier analyses would be most
appropriate, rather than the proportion of subjects in remission at various points
in time.
2) The dose of rifaximin used in this study seems too low, particularly given the
unimpressive results published recently with 400 mg TID in active pouchitis
(Issacs Inflamm Bowel Dis 2007). The authors should justify the selection of this
dose, and also incorporate this newer reference into their discussion. The low
dose of rifaximin should also be acknowledged as a potential limitation of the
present study. For example, it is not clear if the 35% relapse rate by 3 months
was due to rifaximin being a suboptimal drug for these patients, or if the dose
was simply too low. The authors did attempt to analyze the maintenance dose of
rifaximin as a predictor of maintenance of remission and found it to be
non-significant, but the majority of patients in each group only got 200 mg per
day, and 73% of the relapsers discontinued medication within 2 months.
3) The choice of 3 months maintenance also needs to be justified. In other recent
studies (eg the VSL #3 studies), the duration of follow up was longer. This issue
is particularly important given the decreasing rates of maintenance that you
report after 6 and 12 months. It is not clear if these decreasing rates are due to
insufficient follow up or loss of efficacy.
Minor Essential Revisions
1) Patients routinely using NSAID were asked to stop. Was there any wash-out
period between stopping NSAIDs and inclusion in the study? This issue is
important since your group has reported that discontinuation of NSAIDs in
regular users may lead to significant improvement in PDAI.
2) Your results wold be more useful if you could provide some comparative data
(from the literature or from your own practice) on maintenance rates with other
medications (like ciprofloxacin).
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I helped develop and am participating in a study of rifaximin in C. difficile colitis.
As part of that work, I have served as a consultant to Salix (makers of rifaximin).
I have also collaborated with the first author on several pouchitis projects.
I believe I have been able to give a fair assessment of this manuscript despite
these potential conflicts.
Please review this paper.
user
Reviewer's report
Title:Rifaximin for maintenance therapy in antibiotic-dependent pouchitis
Version: 1Date:27 December 2007
Reviewer: Darrell S Pardi
Reviewer's report:
This is a straight-forward study of rifaximin for maintenance of remission in
antibiotic-dependent pouchitis, and the manuscript is well written. I have a few
comments/questions:
Major Compulsory Revisions
1) Given that this is basically a time-to-recurrence study, it would seem that the
construction of survival curves with Kaplan-Meier analyses would be most
appropriate, rather than the proportion of subjects in remission at various points
in time.
2) The dose of rifaximin used in this study seems too low, particularly given the
unimpressive results published recently with 400 mg TID in active pouchitis
(Issacs Inflamm Bowel Dis 2007). The authors should justify the selection of this
dose, and also incorporate this newer reference into their discussion. The low
dose of rifaximin should also be acknowledged as a potential limitation of the
present study. For example, it is not clear if the 35% relapse rate by 3 months
was due to rifaximin being a suboptimal drug for these patients, or if the dose
was simply too low. The authors did attempt to analyze the maintenance dose of
rifaximin as a predictor of maintenance of remission and found it to be
non-significant, but the majority of patients in each group only got 200 mg per
day, and 73% of the relapsers discontinued medication within 2 months.
3) The choice of 3 months maintenance also needs to be justified. In other recent
studies (eg the VSL #3 studies), the duration of follow up was longer. This issue
is particularly important given the decreasing rates of maintenance that you
report after 6 and 12 months. It is not clear if these decreasing rates are due to
insufficient follow up or loss of efficacy.
Minor Essential Revisions
1) Patients routinely using NSAID were asked to stop. Was there any wash-out
period between stopping NSAIDs and inclusion in the study? This issue is
important since your group has reported that discontinuation of NSAIDs in
regular users may lead to significant improvement in PDAI.
2) Your results wold be more useful if you could provide some comparative data
(from the literature or from your own practice) on maintenance rates with other
medications (like ciprofloxacin).
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I helped develop and am participating in a study of rifaximin in C. difficile colitis.
As part of that work, I have served as a consultant to Salix (makers of rifaximin).
I have also collaborated with the first author on several pouchitis projects.
I believe I have been able to give a fair assessment of this manuscript despite
these potential conflicts.
assistant