Title: Effectiveness and safety of vedolizumab induction with or without budesonide in patients
with moderately to severely active Crohn’s disease in Europe: a retrospective observational
study
Version: 1 Date: 27 Jul 2023
Reviewer's report:
This is a retrospective multicentre study across 3 countries which compared the rates of clinical
remission after treattment with VDZ+budesonide versus VDZ alone in moderate-severe Crohn's
disease.
During a  period of 4 years, 123 patients were found from 11 centres (mean 11 patiens per
center). No data are provided on the original pool of patients treated with any drug for moderate-
severe CD.
The two treatment groups  did not differ according to clinical remission rates at week 14, with
very high rates (71.4% vs 68%) which the authors found to be higher than previously reported
in both registrative and real-life studies, as well as in their expected statistical methods (line
184-185).
Budesonide is supported as a treatment for mild-moderate Crohn's disease located at the ileum
and/or right colon. Nonetheless, the authors included patients with other disease extension as
well as patients with more severe disease; therefore, these patients features may be a bias about
the clinical role of adding budesonide which may impact the results on its efficacy. The authors
should stratify their results according to these data.
Duration and dosage of treatment with budesonide is not standardized; even very short courses
("at least one week"- line 101) are included in the study. The sample of patients appear too
heterogeneous, thus providing weak data for a small retrospective study, with high risk of bias.
Other comments:
- line 68: costs should be added as an important criteria for treatment choice in current
socioeconomic healthy real-life, since no studies are conclusive about what drug should be first
choice just according to clinical efficacy
- line 78: the right indication for budesonide is mild-moderate Crohn's disease located at the
ileum and/or right colon. This should be cited
- lines 79-81: the sentence is poor written
- line 87: budesonide is  tested by the authors as an additive treatment to expedite the time to
clinical response; some references on evidences about this property should be provided
- line 220: the specific type of topical corticosteroids should be provided
- line 244: the specific type of gastrointestinal disorders should be mentioned
- what about data on clinical response rates instead of remission rates? any differences in the
two groups?
- line 257: how the authors explain the lower prescription rates in patiemts with prior biologic
use?
In conclusion, I am very interested on the topic analysed by this study, which is the clinical
utility to add a topical steroid like budesonide to support and potentially accelerate the clinical
efficacy of VDZ in Crohn's disease. However, I fear that some important methodological criteria
used by the authors in their selection of patients and treatments can provide significant bias
over those already expected in a small retrospective study. I would focus only on moderate CD
located at ileum and/or right colon; moreover, I would analyse the outcomes in terms of early
clinical response instead of remission: it should be a way to find some clinical utility in terms
of quality of life.
Title: Effectiveness and safety of vedolizumab induction with or without budesonide in patients
with moderately to severely active Crohn’s disease in Europe: a retrospective observational
study
Version: 1 Date: 27 Jul 2023
Reviewer's report:
This is a retrospective multicentre study across 3 countries which compared the rates of clinical
remission after treattment with VDZ+budesonide versus VDZ alone in moderate-severe Crohn's
disease.
During a  period of 4 years, 123 patients were found from 11 centres (mean 11 patiens per
center). No data are provided on the original pool of patients treated with any drug for moderate-
severe CD.
The two treatment groups  did not differ according to clinical remission rates at week 14, with
very high rates (71.4% vs 68%) which the authors found to be higher than previously reported
in both registrative and real-life studies, as well as in their expected statistical methods (line
184-185).
Budesonide is supported as a treatment for mild-moderate Crohn's disease located at the ileum
and/or right colon. Nonetheless, the authors included patients with other disease extension as
well as patients with more severe disease; therefore, these patients features may be a bias about
the clinical role of adding budesonide which may impact the results on its efficacy. The authors
should stratify their results according to these data.
Duration and dosage of treatment with budesonide is not standardized; even very short courses
("at least one week"- line 101) are included in the study. The sample of patients appear too
heterogeneous, thus providing weak data for a small retrospective study, with high risk of bias.
Other comments:
- line 68: costs should be added as an important criteria for treatment choice in current
socioeconomic healthy real-life, since no studies are conclusive about what drug should be first
choice just according to clinical efficacy
- line 78: the right indication for budesonide is mild-moderate Crohn's disease located at the
ileum and/or right colon. This should be cited
- lines 79-81: the sentence is poor written
- line 87: budesonide is  tested by the authors as an additive treatment to expedite the time to
clinical response; some references on evidences about this property should be provided
- line 220: the specific type of topical corticosteroids should be provided
- line 244: the specific type of gastrointestinal disorders should be mentioned
- what about data on clinical response rates instead of remission rates? any differences in the
two groups?
- line 257: how the authors explain the lower prescription rates in patiemts with prior biologic
use?
In conclusion, I am very interested on the topic analysed by this study, which is the clinical
utility to add a topical steroid like budesonide to support and potentially accelerate the clinical
efficacy of VDZ in Crohn's disease. However, I fear that some important methodological criteria
used by the authors in their selection of patients and treatments can provide significant bias
over those already expected in a small retrospective study. I would focus only on moderate CD
located at ileum and/or right colon; moreover, I would analyse the outcomes in terms of early
clinical response instead of remission: it should be a way to find some clinical utility in terms
of quality of life.
Please review this paper.
user
Title: Effectiveness and safety of vedolizumab induction with or without budesonide in patients
with moderately to severely active Crohn’s disease in Europe: a retrospective observational
study
Version: 1 Date: 27 Jul 2023
Reviewer's report:
This is a retrospective multicentre study across 3 countries which compared the rates of clinical
remission after treattment with VDZ+budesonide versus VDZ alone in moderate-severe Crohn's
disease.
During a  period of 4 years, 123 patients were found from 11 centres (mean 11 patiens per
center). No data are provided on the original pool of patients treated with any drug for moderate-
severe CD.
The two treatment groups  did not differ according to clinical remission rates at week 14, with
very high rates (71.4% vs 68%) which the authors found to be higher than previously reported
in both registrative and real-life studies, as well as in their expected statistical methods (line
184-185).
Budesonide is supported as a treatment for mild-moderate Crohn's disease located at the ileum
and/or right colon. Nonetheless, the authors included patients with other disease extension as
well as patients with more severe disease; therefore, these patients features may be a bias about
the clinical role of adding budesonide which may impact the results on its efficacy. The authors
should stratify their results according to these data.
Duration and dosage of treatment with budesonide is not standardized; even very short courses
("at least one week"- line 101) are included in the study. The sample of patients appear too
heterogeneous, thus providing weak data for a small retrospective study, with high risk of bias.
Other comments:
- line 68: costs should be added as an important criteria for treatment choice in current
socioeconomic healthy real-life, since no studies are conclusive about what drug should be first
choice just according to clinical efficacy
- line 78: the right indication for budesonide is mild-moderate Crohn's disease located at the
ileum and/or right colon. This should be cited
- lines 79-81: the sentence is poor written
- line 87: budesonide is  tested by the authors as an additive treatment to expedite the time to
clinical response; some references on evidences about this property should be provided
- line 220: the specific type of topical corticosteroids should be provided
- line 244: the specific type of gastrointestinal disorders should be mentioned
- what about data on clinical response rates instead of remission rates? any differences in the
two groups?
- line 257: how the authors explain the lower prescription rates in patiemts with prior biologic
use?
In conclusion, I am very interested on the topic analysed by this study, which is the clinical
utility to add a topical steroid like budesonide to support and potentially accelerate the clinical
efficacy of VDZ in Crohn's disease. However, I fear that some important methodological criteria
used by the authors in their selection of patients and treatments can provide significant bias
over those already expected in a small retrospective study. I would focus only on moderate CD
located at ileum and/or right colon; moreover, I would analyse the outcomes in terms of early
clinical response instead of remission: it should be a way to find some clinical utility in terms
of quality of life.
assistant