Title: Treatment Sequences, Outcomes, Healthcare Utilization and Costs in Patients with
Inflammatory Bowel Diseases Requiring Advanced Treatment—Real World Comparative
Effectiveness from German Claims Data
Version: 0 Date: 28 Mar 2025
Reviewer's report:
General comments
Utilizing data from claims databases, the study investigated the drug persistence of biologics/
targeted small molecule in treatment of IBD. The research question is clearly clinically relevant
and as such the study is welcomed. In general, the methods are considered appropriate and the
analyses sufficient (please see specific comments below). Considering, the highly selected study
population, the external validity is unclear. The economical analyses are problematic as drug
prices varies from country to country. This is also the case for non-drug related health expenses.
It is unclear if the results can be extrapolated to other settings than Germany. This limitation ( as
well as others) need to be discussed in detail. The manuscript is lengthy and difficult to read.
Specific comments
The manuscript needs thorough linguistic revision by a native English speaker
Introduction
The meaning of the sentence “ For recurring flare-ups, steroid-dependent or steroid refractory
IBD courses conventional treatment escalation should be followed by
initiating advanced therapy [3, 4].” is difficult to understand. Deleting  “courses” would improve
readability.
The introduction is unnecessarily long and full of details not necessary for understanding the
clinical problem. Could be shortened without losing clarity.
Material and methods
For readers unfamiliar with the German health care system, a brief description would be
beneficial. Is there a non-SHI population? Is the SHI population representative of the entire
German population?
“ TTNT is defined as the number of days from index date (start of 1L treatment) to start of
2L treatment or censoring date” Censored patients did not meet the endpoint. The sentence is
misleading. Please rephrase
Statistical analyses
A large number of statistical comparisons were made. Did the authors correct for multiplicity?
Results
Please add a diagram depicting patient disposition. There is quite a big loss of patients not
fulfilling inclusion criteria. What are the implications for the external validity of the study.
Ulcerative colitis: it is assumed that the results are from 1L treatment? If this the case it should
be clearly stated
Discussion is unnecessarily long and complex. Please revise, shorten and simplify.
Title: Treatment Sequences, Outcomes, Healthcare Utilization and Costs in Patients with
Inflammatory Bowel Diseases Requiring Advanced Treatment—Real World Comparative
Effectiveness from German Claims Data
Version: 0 Date: 28 Mar 2025
Reviewer's report:
General comments
Utilizing data from claims databases, the study investigated the drug persistence of biologics/
targeted small molecule in treatment of IBD. The research question is clearly clinically relevant
and as such the study is welcomed. In general, the methods are considered appropriate and the
analyses sufficient (please see specific comments below). Considering, the highly selected study
population, the external validity is unclear. The economical analyses are problematic as drug
prices varies from country to country. This is also the case for non-drug related health expenses.
It is unclear if the results can be extrapolated to other settings than Germany. This limitation ( as
well as others) need to be discussed in detail. The manuscript is lengthy and difficult to read.
Specific comments
The manuscript needs thorough linguistic revision by a native English speaker
Introduction
The meaning of the sentence “ For recurring flare-ups, steroid-dependent or steroid refractory
IBD courses conventional treatment escalation should be followed by
initiating advanced therapy [3, 4].” is difficult to understand. Deleting  “courses” would improve
readability.
The introduction is unnecessarily long and full of details not necessary for understanding the
clinical problem. Could be shortened without losing clarity.
Material and methods
For readers unfamiliar with the German health care system, a brief description would be
beneficial. Is there a non-SHI population? Is the SHI population representative of the entire
German population?
“ TTNT is defined as the number of days from index date (start of 1L treatment) to start of
2L treatment or censoring date” Censored patients did not meet the endpoint. The sentence is
misleading. Please rephrase
Statistical analyses
A large number of statistical comparisons were made. Did the authors correct for multiplicity?
Results
Please add a diagram depicting patient disposition. There is quite a big loss of patients not
fulfilling inclusion criteria. What are the implications for the external validity of the study.
Ulcerative colitis: it is assumed that the results are from 1L treatment? If this the case it should
be clearly stated
Discussion is unnecessarily long and complex. Please revise, shorten and simplify.
Please review this paper.
user
Title: Treatment Sequences, Outcomes, Healthcare Utilization and Costs in Patients with
Inflammatory Bowel Diseases Requiring Advanced Treatment—Real World Comparative
Effectiveness from German Claims Data
Version: 0 Date: 28 Mar 2025
Reviewer's report:
General comments
Utilizing data from claims databases, the study investigated the drug persistence of biologics/
targeted small molecule in treatment of IBD. The research question is clearly clinically relevant
and as such the study is welcomed. In general, the methods are considered appropriate and the
analyses sufficient (please see specific comments below). Considering, the highly selected study
population, the external validity is unclear. The economical analyses are problematic as drug
prices varies from country to country. This is also the case for non-drug related health expenses.
It is unclear if the results can be extrapolated to other settings than Germany. This limitation ( as
well as others) need to be discussed in detail. The manuscript is lengthy and difficult to read.
Specific comments
The manuscript needs thorough linguistic revision by a native English speaker
Introduction
The meaning of the sentence “ For recurring flare-ups, steroid-dependent or steroid refractory
IBD courses conventional treatment escalation should be followed by
initiating advanced therapy [3, 4].” is difficult to understand. Deleting  “courses” would improve
readability.
The introduction is unnecessarily long and full of details not necessary for understanding the
clinical problem. Could be shortened without losing clarity.
Material and methods
For readers unfamiliar with the German health care system, a brief description would be
beneficial. Is there a non-SHI population? Is the SHI population representative of the entire
German population?
“ TTNT is defined as the number of days from index date (start of 1L treatment) to start of
2L treatment or censoring date” Censored patients did not meet the endpoint. The sentence is
misleading. Please rephrase
Statistical analyses
A large number of statistical comparisons were made. Did the authors correct for multiplicity?
Results
Please add a diagram depicting patient disposition. There is quite a big loss of patients not
fulfilling inclusion criteria. What are the implications for the external validity of the study.
Ulcerative colitis: it is assumed that the results are from 1L treatment? If this the case it should
be clearly stated
Discussion is unnecessarily long and complex. Please revise, shorten and simplify.
assistant