Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 24 Dec 2024
Reviewer's report:
The authors have taken a large cohort of patients on biologics with the aim of determining risk
factors for CDI particularly in the IBD cohort. I do have some concerns regarding adjustment
for confounding factors and therefore some of the results and discussion statements. Please see
the points below.
1)  The two cohorts chosen are vastly different. And I think makes it very difficult to
compare beyond saying that biologic therapy does not appear to have an increased risk. This
is acknowledged in the opening discussion sentence, however I don't think all of table 1
information is required. I would also exlcude rheumatology cohort from the reset of the data.
Differences in traditional risk factors, i.e. antibiotic use and PPI use should be included in this
table 1. Given I suspect the skewing of data, median rather than mean should be used to describe
the number of biologics used.
Table 2 should exclude the rheumatology cohort given small numbers and could just add to
skewing - I would keep this to just the IBD cohort.
2) Each table needs a legend. for example, multvariate logistic regression needs the variables
that were included in the multivariable analysis. This appears in the body of the text but also
needs to be in the table. Before presenting multivariable analysis, univariable analysis with all
important variables should also be included.
3) Table 5 and body of the text results: I think there has been a misinterpretation of the data.
referrence appears to be UC, and then the odds ratio is 2? Therefore CD compared to UC has
higher risk? Or is the table the wrong way around?
4) It is interesting that vedolizumab and ustekinumab have the higher incidence of c. diff -
these two biologicals are used infrequently in the rheumatology cohort. Hence another reason
to exclude the rheumatological cohort from further analysis post the initial one.
5) Appropriate adjustment for known confounders needs to happen - i.e. antibiotics and PPI.
Some of the findings here could all be related to confounders. Please redo statistics with listed
confounders.
6) Regarding the discussion point of the number of biologics. Could this not be an indication of
severity of their IBD and therefore potentially more disruption of the gut integrity?
Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 24 Dec 2024
Reviewer's report:
The authors have taken a large cohort of patients on biologics with the aim of determining risk
factors for CDI particularly in the IBD cohort. I do have some concerns regarding adjustment
for confounding factors and therefore some of the results and discussion statements. Please see
the points below.
1)  The two cohorts chosen are vastly different. And I think makes it very difficult to
compare beyond saying that biologic therapy does not appear to have an increased risk. This
is acknowledged in the opening discussion sentence, however I don't think all of table 1
information is required. I would also exlcude rheumatology cohort from the reset of the data.
Differences in traditional risk factors, i.e. antibiotic use and PPI use should be included in this
table 1. Given I suspect the skewing of data, median rather than mean should be used to describe
the number of biologics used.
Table 2 should exclude the rheumatology cohort given small numbers and could just add to
skewing - I would keep this to just the IBD cohort.
2) Each table needs a legend. for example, multvariate logistic regression needs the variables
that were included in the multivariable analysis. This appears in the body of the text but also
needs to be in the table. Before presenting multivariable analysis, univariable analysis with all
important variables should also be included.
3) Table 5 and body of the text results: I think there has been a misinterpretation of the data.
referrence appears to be UC, and then the odds ratio is 2? Therefore CD compared to UC has
higher risk? Or is the table the wrong way around?
4) It is interesting that vedolizumab and ustekinumab have the higher incidence of c. diff -
these two biologicals are used infrequently in the rheumatology cohort. Hence another reason
to exclude the rheumatological cohort from further analysis post the initial one.
5) Appropriate adjustment for known confounders needs to happen - i.e. antibiotics and PPI.
Some of the findings here could all be related to confounders. Please redo statistics with listed
confounders.
6) Regarding the discussion point of the number of biologics. Could this not be an indication of
severity of their IBD and therefore potentially more disruption of the gut integrity?
Please review this paper.
user
Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 24 Dec 2024
Reviewer's report:
The authors have taken a large cohort of patients on biologics with the aim of determining risk
factors for CDI particularly in the IBD cohort. I do have some concerns regarding adjustment
for confounding factors and therefore some of the results and discussion statements. Please see
the points below.
1)  The two cohorts chosen are vastly different. And I think makes it very difficult to
compare beyond saying that biologic therapy does not appear to have an increased risk. This
is acknowledged in the opening discussion sentence, however I don't think all of table 1
information is required. I would also exlcude rheumatology cohort from the reset of the data.
Differences in traditional risk factors, i.e. antibiotic use and PPI use should be included in this
table 1. Given I suspect the skewing of data, median rather than mean should be used to describe
the number of biologics used.
Table 2 should exclude the rheumatology cohort given small numbers and could just add to
skewing - I would keep this to just the IBD cohort.
2) Each table needs a legend. for example, multvariate logistic regression needs the variables
that were included in the multivariable analysis. This appears in the body of the text but also
needs to be in the table. Before presenting multivariable analysis, univariable analysis with all
important variables should also be included.
3) Table 5 and body of the text results: I think there has been a misinterpretation of the data.
referrence appears to be UC, and then the odds ratio is 2? Therefore CD compared to UC has
higher risk? Or is the table the wrong way around?
4) It is interesting that vedolizumab and ustekinumab have the higher incidence of c. diff -
these two biologicals are used infrequently in the rheumatology cohort. Hence another reason
to exclude the rheumatological cohort from further analysis post the initial one.
5) Appropriate adjustment for known confounders needs to happen - i.e. antibiotics and PPI.
Some of the findings here could all be related to confounders. Please redo statistics with listed
confounders.
6) Regarding the discussion point of the number of biologics. Could this not be an indication of
severity of their IBD and therefore potentially more disruption of the gut integrity?
assistant