Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 29 Dec 2024
Reviewer:  Sasha R. Fehily
Reviewer's report:
This is very useful data in improving the understanding of CDI risk in a large IBD cohort.
Some revision considerations:
Please include how the medication data was collected ?prescriptions. Was dosing variability
across cohorts assessed ie was dosing/frequency and compassionate drug access recorded as
cumulative exposure may have been higher in IBD cohorts.
Asymptomatic carriage is higher in IBD patients likely due to more frequent stool testing. Were
specific criteria used to differentiate infections from colonization? Were asymptomatic carriers
excluded from the analysis?
Details on rationale for choosing the CDI severity score. Has this been validated in IBD cohorts.
You have tabulated more data that could have been included in more comprehensive CDI
severity score.
Re vedolizumab and ustekinumab, these drugs are widely recognized as options for first-line
therapy in international guidelines. Details surrounding the rationale for these agents not being
used first line / in refractory patients should be included as this impact’s the generalisability of
the data.
Were the patients in the "without biologics" group using immunomodulators, 5-asa,
corticosteroids? A subgroup analysis (biologic therapy vs. vs. immunomodulator vs.
corticosteroids vs. 5-ASA vs. no therapy) may demonstrate a difference.
While disease severity was not assessed, retrospective evaluation of disease severity within 3-6
months before CDI would provide valuable context as to whether the drug or disease activity
is driving the risk, an important distinction.
The current Montreal classification could be used to compare whether there is a difference in risk
between UC and Crohn's colitis. The statement about colonic involvement and CDI risk appears
overstated if it is not directly presented in the data. Clarification is needed, or the language
should be revised to indicate that this was an assumption rather than a finding.
Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 29 Dec 2024
Reviewer:  Sasha R. Fehily
Reviewer's report:
This is very useful data in improving the understanding of CDI risk in a large IBD cohort.
Some revision considerations:
Please include how the medication data was collected ?prescriptions. Was dosing variability
across cohorts assessed ie was dosing/frequency and compassionate drug access recorded as
cumulative exposure may have been higher in IBD cohorts.
Asymptomatic carriage is higher in IBD patients likely due to more frequent stool testing. Were
specific criteria used to differentiate infections from colonization? Were asymptomatic carriers
excluded from the analysis?
Details on rationale for choosing the CDI severity score. Has this been validated in IBD cohorts.
You have tabulated more data that could have been included in more comprehensive CDI
severity score.
Re vedolizumab and ustekinumab, these drugs are widely recognized as options for first-line
therapy in international guidelines. Details surrounding the rationale for these agents not being
used first line / in refractory patients should be included as this impact’s the generalisability of
the data.
Were the patients in the "without biologics" group using immunomodulators, 5-asa,
corticosteroids? A subgroup analysis (biologic therapy vs. vs. immunomodulator vs.
corticosteroids vs. 5-ASA vs. no therapy) may demonstrate a difference.
While disease severity was not assessed, retrospective evaluation of disease severity within 3-6
months before CDI would provide valuable context as to whether the drug or disease activity
is driving the risk, an important distinction.
The current Montreal classification could be used to compare whether there is a difference in risk
between UC and Crohn's colitis. The statement about colonic involvement and CDI risk appears
overstated if it is not directly presented in the data. Clarification is needed, or the language
should be revised to indicate that this was an assumption rather than a finding.
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: 29 Dec 2024
Reviewer:  Sasha R. Fehily
Reviewer's report:
This is very useful data in improving the understanding of CDI risk in a large IBD cohort.
Some revision considerations:
Please include how the medication data was collected ?prescriptions. Was dosing variability
across cohorts assessed ie was dosing/frequency and compassionate drug access recorded as
cumulative exposure may have been higher in IBD cohorts.
Asymptomatic carriage is higher in IBD patients likely due to more frequent stool testing. Were
specific criteria used to differentiate infections from colonization? Were asymptomatic carriers
excluded from the analysis?
Details on rationale for choosing the CDI severity score. Has this been validated in IBD cohorts.
You have tabulated more data that could have been included in more comprehensive CDI
severity score.
Re vedolizumab and ustekinumab, these drugs are widely recognized as options for first-line
therapy in international guidelines. Details surrounding the rationale for these agents not being
used first line / in refractory patients should be included as this impact’s the generalisability of
the data.
Were the patients in the "without biologics" group using immunomodulators, 5-asa,
corticosteroids? A subgroup analysis (biologic therapy vs. vs. immunomodulator vs.
corticosteroids vs. 5-ASA vs. no therapy) may demonstrate a difference.
While disease severity was not assessed, retrospective evaluation of disease severity within 3-6
months before CDI would provide valuable context as to whether the drug or disease activity
is driving the risk, an important distinction.
The current Montreal classification could be used to compare whether there is a difference in risk
between UC and Crohn's colitis. The statement about colonic involvement and CDI risk appears
overstated if it is not directly presented in the data. Clarification is needed, or the language
should be revised to indicate that this was an assumption rather than a finding.
assistant