Title: A retrospective, observational study to examine the effect of early tumor necrosis factor
inhibitor use on rates of surgery for Crohn’s disease in Japan
Version: 3 Date: 05 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The author(s) have written a very nice rebuttal that helped me to
navigate through the comments easily. The point to point reply is in fact one of the better
compared to those that I have been seen lately
ADDITIONAL REQUESTS/SUGGESTIONS:
The authors state that their data are  of value to determine the effect (size sic)  in the clinical
setting. The argument that I would like to make (banking on this argument ) is that there are
prospective registries and/or clinical trials that have collected a wealth of data. The novelty lies in
the safety / efficacy assessment in their setting and perhaps the comparison between adalumimab
and infliximab (see reviewer #1)
The authors rightfully acknowledge the limitations of a retrospective study, and this
methodology comes with real drawbacks as the authors are unable to retrospectively classify the
patients according to the Montreal classification.
The matched analysis is a fine addition to the manuscript and bolsters the case made by the
authors    .
Last but not least , the observational period (with follow up) is long, and this comes with
advantages. I appreciate the fact that the authors have performed a restricted analysis to patients
diagnosed after 2002 and followed at least 5 years. This in essence bolsters their results.
Given the advent of the new small molecules for inflammatory bowel disease it is to be expected
that its  management will expand beyond that of TNF inhibitors. While it is unsure whether that
will impact surgery rates, the current analysis is helpful.
Title: A retrospective, observational study to examine the effect of early tumor necrosis factor
inhibitor use on rates of surgery for Crohn’s disease in Japan
Version: 3 Date: 05 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The author(s) have written a very nice rebuttal that helped me to
navigate through the comments easily. The point to point reply is in fact one of the better
compared to those that I have been seen lately
ADDITIONAL REQUESTS/SUGGESTIONS:
The authors state that their data are  of value to determine the effect (size sic)  in the clinical
setting. The argument that I would like to make (banking on this argument ) is that there are
prospective registries and/or clinical trials that have collected a wealth of data. The novelty lies in
the safety / efficacy assessment in their setting and perhaps the comparison between adalumimab
and infliximab (see reviewer #1)
The authors rightfully acknowledge the limitations of a retrospective study, and this
methodology comes with real drawbacks as the authors are unable to retrospectively classify the
patients according to the Montreal classification.
The matched analysis is a fine addition to the manuscript and bolsters the case made by the
authors    .
Last but not least , the observational period (with follow up) is long, and this comes with
advantages. I appreciate the fact that the authors have performed a restricted analysis to patients
diagnosed after 2002 and followed at least 5 years. This in essence bolsters their results.
Given the advent of the new small molecules for inflammatory bowel disease it is to be expected
that its  management will expand beyond that of TNF inhibitors. While it is unsure whether that
will impact surgery rates, the current analysis is helpful.
Please review this paper.
user
Title: A retrospective, observational study to examine the effect of early tumor necrosis factor
inhibitor use on rates of surgery for Crohn’s disease in Japan
Version: 3 Date: 05 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The author(s) have written a very nice rebuttal that helped me to
navigate through the comments easily. The point to point reply is in fact one of the better
compared to those that I have been seen lately
ADDITIONAL REQUESTS/SUGGESTIONS:
The authors state that their data are  of value to determine the effect (size sic)  in the clinical
setting. The argument that I would like to make (banking on this argument ) is that there are
prospective registries and/or clinical trials that have collected a wealth of data. The novelty lies in
the safety / efficacy assessment in their setting and perhaps the comparison between adalumimab
and infliximab (see reviewer #1)
The authors rightfully acknowledge the limitations of a retrospective study, and this
methodology comes with real drawbacks as the authors are unable to retrospectively classify the
patients according to the Montreal classification.
The matched analysis is a fine addition to the manuscript and bolsters the case made by the
authors    .
Last but not least , the observational period (with follow up) is long, and this comes with
advantages. I appreciate the fact that the authors have performed a restricted analysis to patients
diagnosed after 2002 and followed at least 5 years. This in essence bolsters their results.
Given the advent of the new small molecules for inflammatory bowel disease it is to be expected
that its  management will expand beyond that of TNF inhibitors. While it is unsure whether that
will impact surgery rates, the current analysis is helpful.
assistant