Reviewer’s report
Title: 
Combined therapy with early initiation of infliximab following drainage of
perianal fistulising Crohn’s disease  a retrospective cohort study
Version: 
0 
Date: 
05 Sep 2021
Reviewer's report:
Thank you to the authors for their submission of a manuscript describing the
experience of perianal Crohn's disease management a single tertiary centre, an
important topic. Comments regarding the manuscript are below.
Terminology
- Use of the term combination may be confusing for readers - could be inferred
as meaning combination infliximab with an immunomodulator; suggest
consideration of alternative terminology eg early or delayed infliximab induction
(given delay is more so relating to the infliximab commencement vs the
multidisciplinary management)
- presentation of numbers in words if ten or less eg 2-3 months = two to three
months
- consistent use of acronyms throughout text eg PFCD 
- inconsistency of use of tense (past and present tense interchangeably used)
- additional typographical errors: please perform further editing and proof
reading
Abstract
- Maintenance infliximab therapy > 3 times: what does this mean ?at least three
maintenance infliximab doses
- Presence of abscess also negatively influenced (vs influence) 
- an example of
the need to maintain consistent tense
- Conclusion: how is the superiority of early initiation of infliximab therapy
demonstrated when no statistical difference apparent between the two treatment
groups
Background
Outcome
- Suggest rewording: We also aim to identify predictive factors associated with
fistula closure and the need for surgical reintervention within the early
combination (or ?infliximab group if terminology to change)
Methods
- There are multiple classification systems in the AGA review that has been
cited; please be more specific and cite the original article for the classification
system that was used eg Parkes
- Who assessed for fistula closure ?was it a patient reported outcome or assessed
via examination; is the outcome being referred to closure or is it healing? 
- Define SD
- It is unclear what determined the timing of infliximab commencement - I
presume at the discretion of the physician however what factors influenced this
decision, and have they been accounted for in the analysis; I am concerned that
the comparative results will be confounded by the underlying reasons for the
decision early vs delayed timing of infliximab 
- Analysis: ?why not consider a MV analysis of factors that influence fistula
closure and have as one of the factors the timing of infliximab commencement to
determine the impact of the timing; the obvious limitation of this is that surgical
procedures were specifically performed in the delayed group to facilitate closure;
is it possible to have a sub-analysis and exclude patients who underwent surgical
procedures beyond seton insertion to help further assess this question?
- No data about the use of antibiotics - given the impact on short/medium term
outcomes, this is critical
- Suggest comment regarding the prescribing restrictions in China regarding the
use of maintenance infliximab here (vs leaving to discussion)
Results
- Presumably there are differences between the two groups (which haven't been
identified) that have resulted in the choice of seton insertion vs fistulotomy/other
surgical intervention; ie merely classifying as complex (Y or N) is not
accounting for differences in fistula morphology and resultant surgical
interventions; such unaccounted differences could be the explanation as to why
there was early vs delayed induction with IFX
- All BMIs <20 ?is this of concern or reflection of issues with the application of
BMI to Chinese population
- Difference in follow up about ~ 6months ?why ?impact
- Multivariate analysis includes presence of abscess at baseline (vs the indication
for reintervention) = this needs to be clearer in the table please
- I cannot find data regarding proportion of patients with seton removal; how can
fistula closure be achieved in the presence of a seton and accordingly has this
influenced outcomes? 
Publons Reviewer Recognition
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find the details of processing in Publons’ privacy policy
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Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
Nil
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Combined therapy with early initiation of infliximab following drainage of
perianal fistulising Crohn’s disease  a retrospective cohort study
Version: 
0 
Date: 
05 Sep 2021
Reviewer's report:
Thank you to the authors for their submission of a manuscript describing the
experience of perianal Crohn's disease management a single tertiary centre, an
important topic. Comments regarding the manuscript are below.
Terminology
- Use of the term combination may be confusing for readers - could be inferred
as meaning combination infliximab with an immunomodulator; suggest
consideration of alternative terminology eg early or delayed infliximab induction
(given delay is more so relating to the infliximab commencement vs the
multidisciplinary management)
- presentation of numbers in words if ten or less eg 2-3 months = two to three
months
- consistent use of acronyms throughout text eg PFCD 
- inconsistency of use of tense (past and present tense interchangeably used)
- additional typographical errors: please perform further editing and proof
reading
Abstract
- Maintenance infliximab therapy > 3 times: what does this mean ?at least three
maintenance infliximab doses
- Presence of abscess also negatively influenced (vs influence) 
- an example of
the need to maintain consistent tense
- Conclusion: how is the superiority of early initiation of infliximab therapy
demonstrated when no statistical difference apparent between the two treatment
groups
Background
Outcome
- Suggest rewording: We also aim to identify predictive factors associated with
fistula closure and the need for surgical reintervention within the early
combination (or ?infliximab group if terminology to change)
Methods
- There are multiple classification systems in the AGA review that has been
cited; please be more specific and cite the original article for the classification
system that was used eg Parkes
- Who assessed for fistula closure ?was it a patient reported outcome or assessed
via examination; is the outcome being referred to closure or is it healing? 
- Define SD
- It is unclear what determined the timing of infliximab commencement - I
presume at the discretion of the physician however what factors influenced this
decision, and have they been accounted for in the analysis; I am concerned that
the comparative results will be confounded by the underlying reasons for the
decision early vs delayed timing of infliximab 
- Analysis: ?why not consider a MV analysis of factors that influence fistula
closure and have as one of the factors the timing of infliximab commencement to
determine the impact of the timing; the obvious limitation of this is that surgical
procedures were specifically performed in the delayed group to facilitate closure;
is it possible to have a sub-analysis and exclude patients who underwent surgical
procedures beyond seton insertion to help further assess this question?
- No data about the use of antibiotics - given the impact on short/medium term
outcomes, this is critical
- Suggest comment regarding the prescribing restrictions in China regarding the
use of maintenance infliximab here (vs leaving to discussion)
Results
- Presumably there are differences between the two groups (which haven't been
identified) that have resulted in the choice of seton insertion vs fistulotomy/other
surgical intervention; ie merely classifying as complex (Y or N) is not
accounting for differences in fistula morphology and resultant surgical
interventions; such unaccounted differences could be the explanation as to why
there was early vs delayed induction with IFX
- All BMIs <20 ?is this of concern or reflection of issues with the application of
BMI to Chinese population
- Difference in follow up about ~ 6months ?why ?impact
- Multivariate analysis includes presence of abscess at baseline (vs the indication
for reintervention) = this needs to be clearer in the table please
- I cannot find data regarding proportion of patients with seton removal; how can
fistula closure be achieved in the presence of a seton and accordingly has this
influenced outcomes? 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
Nil
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Combined therapy with early initiation of infliximab following drainage of
perianal fistulising Crohn’s disease  a retrospective cohort study
Version: 
0 
Date: 
05 Sep 2021
Reviewer's report:
Thank you to the authors for their submission of a manuscript describing the
experience of perianal Crohn's disease management a single tertiary centre, an
important topic. Comments regarding the manuscript are below.
Terminology
- Use of the term combination may be confusing for readers - could be inferred
as meaning combination infliximab with an immunomodulator; suggest
consideration of alternative terminology eg early or delayed infliximab induction
(given delay is more so relating to the infliximab commencement vs the
multidisciplinary management)
- presentation of numbers in words if ten or less eg 2-3 months = two to three
months
- consistent use of acronyms throughout text eg PFCD 
- inconsistency of use of tense (past and present tense interchangeably used)
- additional typographical errors: please perform further editing and proof
reading
Abstract
- Maintenance infliximab therapy > 3 times: what does this mean ?at least three
maintenance infliximab doses
- Presence of abscess also negatively influenced (vs influence) 
- an example of
the need to maintain consistent tense
- Conclusion: how is the superiority of early initiation of infliximab therapy
demonstrated when no statistical difference apparent between the two treatment
groups
Background
Outcome
- Suggest rewording: We also aim to identify predictive factors associated with
fistula closure and the need for surgical reintervention within the early
combination (or ?infliximab group if terminology to change)
Methods
- There are multiple classification systems in the AGA review that has been
cited; please be more specific and cite the original article for the classification
system that was used eg Parkes
- Who assessed for fistula closure ?was it a patient reported outcome or assessed
via examination; is the outcome being referred to closure or is it healing? 
- Define SD
- It is unclear what determined the timing of infliximab commencement - I
presume at the discretion of the physician however what factors influenced this
decision, and have they been accounted for in the analysis; I am concerned that
the comparative results will be confounded by the underlying reasons for the
decision early vs delayed timing of infliximab 
- Analysis: ?why not consider a MV analysis of factors that influence fistula
closure and have as one of the factors the timing of infliximab commencement to
determine the impact of the timing; the obvious limitation of this is that surgical
procedures were specifically performed in the delayed group to facilitate closure;
is it possible to have a sub-analysis and exclude patients who underwent surgical
procedures beyond seton insertion to help further assess this question?
- No data about the use of antibiotics - given the impact on short/medium term
outcomes, this is critical
- Suggest comment regarding the prescribing restrictions in China regarding the
use of maintenance infliximab here (vs leaving to discussion)
Results
- Presumably there are differences between the two groups (which haven't been
identified) that have resulted in the choice of seton insertion vs fistulotomy/other
surgical intervention; ie merely classifying as complex (Y or N) is not
accounting for differences in fistula morphology and resultant surgical
interventions; such unaccounted differences could be the explanation as to why
there was early vs delayed induction with IFX
- All BMIs <20 ?is this of concern or reflection of issues with the application of
BMI to Chinese population
- Difference in follow up about ~ 6months ?why ?impact
- Multivariate analysis includes presence of abscess at baseline (vs the indication
for reintervention) = this needs to be clearer in the table please
- I cannot find data regarding proportion of patients with seton removal; how can
fistula closure be achieved in the presence of a seton and accordingly has this
influenced outcomes? 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
Nil
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant