Title: Superior Persistence of Ustekinumab Compared to Anti-TNF in Vedolizumab-
Experienced Inflammatory Bowel Diseases Patients: A Real- world Cohort Study
Version: 1 Date: 03 Dec 2024
Reviewer's report:
The authors compared the persistence of UST and anti-TNF therapies in IBD patients who were
previously exposed to VDZ. There are two major limitations in this study:
1. Lack of effectiveness outcomes: The study does not report key effectiveness outcomes, such as
endoscopic or clinical responses. While therapy persistence is an important measure, it does not
provide a complete picture of the therapy's benefit without evaluating these additional outcomes.
2. Dose escalation and bias in persistence: UST was associated with longer therapy persistence
in this study. However, UST-treated patients also had higher rates of dose escalation. Since it is
well-known that dose escalation can improve outcomes and persistence, it is possible that anti-
TNF-treated patients were not given the same opportunity for dose escalation as UST-treated
patients. The manuscript does not clarify the criteria for dose escalation or whether anti-TNF
serum levels and antibodies were measured. Patients might have developed immunogenicity and
required higher dosing or the addition of immunomodulators, but this information is missing.
Additional remarks for the authors to consider:
Methods:
• Were these patients exclusively exposed to VDZ prior to starting UST or anti-TNF therapy?
If so, this should be explicitly stated in the manuscript.
• What were the exclusion criteria? How many patients were excluded based on each criterion?
• Were the screened patients included consecutively?
• I strongly recommend following the STROBE checklist and including a completed version
with the revised submission.
• The Methods section should be reorganized into subsections, such as: Cohort, Collected
Variables, Outcomes, Statistics, etc.
• To identify predictors of 52-week treatment persistence, Cox proportional hazards models
should be used instead of logistic regression, as the outcome is “time to event.”
• How were cases handled where patients experienced flares requiring hospitalization and
received intravenous steroids or other therapies but continued their index therapy (UST or anti-
TNF)? Similarly, how were cases managed where patients underwent surgery but maintained
their index therapy? Were these situations considered therapy persistence, and were such cases
recorded?
Results:
There appears to be a coding or statistical error in the reported hazard ratios (HR). The
manuscript states that UST exhibited longer persistence in the overall IBD cohort as well as in
the CD and UC sub-cohorts. However, the reported HR values are >1, which is incorrect.
• An HR >1 indicates an increased hazard for the undesirable outcome (therapy discontinuation),
which contradicts the claim that UST is associated with longer persistence.
• If UST was indeed associated with longer persistence, the HR values should fall between 0
and 1. Any values outside this range suggest a coding or calculation error.
Title: Superior Persistence of Ustekinumab Compared to Anti-TNF in Vedolizumab-
Experienced Inflammatory Bowel Diseases Patients: A Real- world Cohort Study
Version: 1 Date: 03 Dec 2024
Reviewer's report:
The authors compared the persistence of UST and anti-TNF therapies in IBD patients who were
previously exposed to VDZ. There are two major limitations in this study:
1. Lack of effectiveness outcomes: The study does not report key effectiveness outcomes, such as
endoscopic or clinical responses. While therapy persistence is an important measure, it does not
provide a complete picture of the therapy's benefit without evaluating these additional outcomes.
2. Dose escalation and bias in persistence: UST was associated with longer therapy persistence
in this study. However, UST-treated patients also had higher rates of dose escalation. Since it is
well-known that dose escalation can improve outcomes and persistence, it is possible that anti-
TNF-treated patients were not given the same opportunity for dose escalation as UST-treated
patients. The manuscript does not clarify the criteria for dose escalation or whether anti-TNF
serum levels and antibodies were measured. Patients might have developed immunogenicity and
required higher dosing or the addition of immunomodulators, but this information is missing.
Additional remarks for the authors to consider:
Methods:
• Were these patients exclusively exposed to VDZ prior to starting UST or anti-TNF therapy?
If so, this should be explicitly stated in the manuscript.
• What were the exclusion criteria? How many patients were excluded based on each criterion?
• Were the screened patients included consecutively?
• I strongly recommend following the STROBE checklist and including a completed version
with the revised submission.
• The Methods section should be reorganized into subsections, such as: Cohort, Collected
Variables, Outcomes, Statistics, etc.
• To identify predictors of 52-week treatment persistence, Cox proportional hazards models
should be used instead of logistic regression, as the outcome is “time to event.”
• How were cases handled where patients experienced flares requiring hospitalization and
received intravenous steroids or other therapies but continued their index therapy (UST or anti-
TNF)? Similarly, how were cases managed where patients underwent surgery but maintained
their index therapy? Were these situations considered therapy persistence, and were such cases
recorded?
Results:
There appears to be a coding or statistical error in the reported hazard ratios (HR). The
manuscript states that UST exhibited longer persistence in the overall IBD cohort as well as in
the CD and UC sub-cohorts. However, the reported HR values are >1, which is incorrect.
• An HR >1 indicates an increased hazard for the undesirable outcome (therapy discontinuation),
which contradicts the claim that UST is associated with longer persistence.
• If UST was indeed associated with longer persistence, the HR values should fall between 0
and 1. Any values outside this range suggest a coding or calculation error.
Please review this paper.
user
Title: Superior Persistence of Ustekinumab Compared to Anti-TNF in Vedolizumab-
Experienced Inflammatory Bowel Diseases Patients: A Real- world Cohort Study
Version: 1 Date: 03 Dec 2024
Reviewer's report:
The authors compared the persistence of UST and anti-TNF therapies in IBD patients who were
previously exposed to VDZ. There are two major limitations in this study:
1. Lack of effectiveness outcomes: The study does not report key effectiveness outcomes, such as
endoscopic or clinical responses. While therapy persistence is an important measure, it does not
provide a complete picture of the therapy's benefit without evaluating these additional outcomes.
2. Dose escalation and bias in persistence: UST was associated with longer therapy persistence
in this study. However, UST-treated patients also had higher rates of dose escalation. Since it is
well-known that dose escalation can improve outcomes and persistence, it is possible that anti-
TNF-treated patients were not given the same opportunity for dose escalation as UST-treated
patients. The manuscript does not clarify the criteria for dose escalation or whether anti-TNF
serum levels and antibodies were measured. Patients might have developed immunogenicity and
required higher dosing or the addition of immunomodulators, but this information is missing.
Additional remarks for the authors to consider:
Methods:
• Were these patients exclusively exposed to VDZ prior to starting UST or anti-TNF therapy?
If so, this should be explicitly stated in the manuscript.
• What were the exclusion criteria? How many patients were excluded based on each criterion?
• Were the screened patients included consecutively?
• I strongly recommend following the STROBE checklist and including a completed version
with the revised submission.
• The Methods section should be reorganized into subsections, such as: Cohort, Collected
Variables, Outcomes, Statistics, etc.
• To identify predictors of 52-week treatment persistence, Cox proportional hazards models
should be used instead of logistic regression, as the outcome is “time to event.”
• How were cases handled where patients experienced flares requiring hospitalization and
received intravenous steroids or other therapies but continued their index therapy (UST or anti-
TNF)? Similarly, how were cases managed where patients underwent surgery but maintained
their index therapy? Were these situations considered therapy persistence, and were such cases
recorded?
Results:
There appears to be a coding or statistical error in the reported hazard ratios (HR). The
manuscript states that UST exhibited longer persistence in the overall IBD cohort as well as in
the CD and UC sub-cohorts. However, the reported HR values are >1, which is incorrect.
• An HR >1 indicates an increased hazard for the undesirable outcome (therapy discontinuation),
which contradicts the claim that UST is associated with longer persistence.
• If UST was indeed associated with longer persistence, the HR values should fall between 0
and 1. Any values outside this range suggest a coding or calculation error.
assistant