Title: Risk of Clostridioides difficile infection in inflammatory bowel disease patients
undergoing vedolizumab treatment: a systematic review and meta-analysis
Version: 1 Date: 26 Jul 2024
Reviewer's report:
Review of the manuscript:
Risk of clostridium difficile infection in inflammatory bowel Disease patients undergoing
vedolizumab treatment: a systematic review and meta-analysis
Thank you for the kind invitation.
This is a systemic review and meta-analysis about a common problem among IBD patients. Due
to its gut-selectivity, vedolizumab has been linked to Clostridium Difficile (C Diff) infection.
The risk of C Diff infection for IBD patients on vedolizumab, was found to be rather low.
Although no statistical significance was reached, vedolizumab was related to less infections
compared to anti-TNFs and more, compared to steroids and 5-ASA.
The data are weak mainly due to the high heterogeneity of included studies and this is pointed
out by the authors. Evidence in patients with IBD is mostly indirect, since C Diff infection is
usually reported as a secondary outcome.
Among the strengths of the study are its subject of high importance for every day clinical
practice, as well as the large number of patients.  A few spelling mistakes need the authors’
attention.
Additionally, I would kindly ask the authors to comment on the following points:
1. Why were patients with pouchitis and postoperative Crohn’s excluded?
2. Are there any data about subcutaneous vedolizumab regarding C Diff infection?
3. Do the duration and dose of vedolizumab affect the risk of the infection?
4. Given that the incidence of C Diff infection is increased in IBD patients, does activity of the
disease play the most important role? Did any associations with activity and/or age emerge from
the included studies?
5. The incidence of C Diff infection among UC patients on vedolizumab, was shown to be higher
than in the CD population. Colonic involvement in UC partly accounts for this.  Vedolizumab
is possibly offered in milder CD cases, whereas it is one of the recommended first -line options
in moderate UC.  Please comment.
6. No difference was found between vedolizumab and anti-TNFs regarding C Diff infection.
However, CD patients under vedolizumab experienced higher risk of C Diff infection compared
to their anti-TNF counterparts. Again, inadequate control of the inflammation may have
accounted for the increased risk.  Please comment.
Unless prospective studies are performed, considering all the possible confounding factors, no
safe conclusions can be drawn. However, data collection and analysis are always appreciated
and are rather reassuring according to the present study. I would like for the authors to expand
on the manuscript’s discussion, taking into account the above-mentioned points.
Title: Risk of Clostridioides difficile infection in inflammatory bowel disease patients
undergoing vedolizumab treatment: a systematic review and meta-analysis
Version: 1 Date: 26 Jul 2024
Reviewer's report:
Review of the manuscript:
Risk of clostridium difficile infection in inflammatory bowel Disease patients undergoing
vedolizumab treatment: a systematic review and meta-analysis
Thank you for the kind invitation.
This is a systemic review and meta-analysis about a common problem among IBD patients. Due
to its gut-selectivity, vedolizumab has been linked to Clostridium Difficile (C Diff) infection.
The risk of C Diff infection for IBD patients on vedolizumab, was found to be rather low.
Although no statistical significance was reached, vedolizumab was related to less infections
compared to anti-TNFs and more, compared to steroids and 5-ASA.
The data are weak mainly due to the high heterogeneity of included studies and this is pointed
out by the authors. Evidence in patients with IBD is mostly indirect, since C Diff infection is
usually reported as a secondary outcome.
Among the strengths of the study are its subject of high importance for every day clinical
practice, as well as the large number of patients.  A few spelling mistakes need the authors’
attention.
Additionally, I would kindly ask the authors to comment on the following points:
1. Why were patients with pouchitis and postoperative Crohn’s excluded?
2. Are there any data about subcutaneous vedolizumab regarding C Diff infection?
3. Do the duration and dose of vedolizumab affect the risk of the infection?
4. Given that the incidence of C Diff infection is increased in IBD patients, does activity of the
disease play the most important role? Did any associations with activity and/or age emerge from
the included studies?
5. The incidence of C Diff infection among UC patients on vedolizumab, was shown to be higher
than in the CD population. Colonic involvement in UC partly accounts for this.  Vedolizumab
is possibly offered in milder CD cases, whereas it is one of the recommended first -line options
in moderate UC.  Please comment.
6. No difference was found between vedolizumab and anti-TNFs regarding C Diff infection.
However, CD patients under vedolizumab experienced higher risk of C Diff infection compared
to their anti-TNF counterparts. Again, inadequate control of the inflammation may have
accounted for the increased risk.  Please comment.
Unless prospective studies are performed, considering all the possible confounding factors, no
safe conclusions can be drawn. However, data collection and analysis are always appreciated
and are rather reassuring according to the present study. I would like for the authors to expand
on the manuscript’s discussion, taking into account the above-mentioned points.
Please review this paper.
user
Title: Risk of Clostridioides difficile infection in inflammatory bowel disease patients
undergoing vedolizumab treatment: a systematic review and meta-analysis
Version: 1 Date: 26 Jul 2024
Reviewer's report:
Review of the manuscript:
Risk of clostridium difficile infection in inflammatory bowel Disease patients undergoing
vedolizumab treatment: a systematic review and meta-analysis
Thank you for the kind invitation.
This is a systemic review and meta-analysis about a common problem among IBD patients. Due
to its gut-selectivity, vedolizumab has been linked to Clostridium Difficile (C Diff) infection.
The risk of C Diff infection for IBD patients on vedolizumab, was found to be rather low.
Although no statistical significance was reached, vedolizumab was related to less infections
compared to anti-TNFs and more, compared to steroids and 5-ASA.
The data are weak mainly due to the high heterogeneity of included studies and this is pointed
out by the authors. Evidence in patients with IBD is mostly indirect, since C Diff infection is
usually reported as a secondary outcome.
Among the strengths of the study are its subject of high importance for every day clinical
practice, as well as the large number of patients.  A few spelling mistakes need the authors’
attention.
Additionally, I would kindly ask the authors to comment on the following points:
1. Why were patients with pouchitis and postoperative Crohn’s excluded?
2. Are there any data about subcutaneous vedolizumab regarding C Diff infection?
3. Do the duration and dose of vedolizumab affect the risk of the infection?
4. Given that the incidence of C Diff infection is increased in IBD patients, does activity of the
disease play the most important role? Did any associations with activity and/or age emerge from
the included studies?
5. The incidence of C Diff infection among UC patients on vedolizumab, was shown to be higher
than in the CD population. Colonic involvement in UC partly accounts for this.  Vedolizumab
is possibly offered in milder CD cases, whereas it is one of the recommended first -line options
in moderate UC.  Please comment.
6. No difference was found between vedolizumab and anti-TNFs regarding C Diff infection.
However, CD patients under vedolizumab experienced higher risk of C Diff infection compared
to their anti-TNF counterparts. Again, inadequate control of the inflammation may have
accounted for the increased risk.  Please comment.
Unless prospective studies are performed, considering all the possible confounding factors, no
safe conclusions can be drawn. However, data collection and analysis are always appreciated
and are rather reassuring according to the present study. I would like for the authors to expand
on the manuscript’s discussion, taking into account the above-mentioned points.
assistant