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: 23 Mar 2025
Reviewer:  Christian Agboton
Reviewer's report:
This is a an interesting paper addressing the notion of sequences of therapies in IBD, a topic that
is more and more prevalent given the large number of drugs available.
The authors managed to avoid the  main pitfalls in this type of analyses by having a precise
definition of sequences and applying propensity score matching  to ensure comparability across
the treatments.
The  results are largely in line with the recently published results, especially for vedolizumab.
The Discussion part is well done with a good summary of the evidence available so far.
The use of "inadequate response" is a novel approach to treatment evaluation.
I would just suggest adding :
- 1. Gros B, Ross H, Nwabueze M, Constantine-Cooke N, Derikx LAAP, Lyons M, et al. Long-
term outcomes and predictors of vedolizumab persistence in ulcerative colitis. Therap Adv
Gastroenterol. 2024;17:17562848241258372.
-2. Bouguen M.D.- PhD. G, Nachury M, Nancey S, Bouhnik Y, Bourreille A, Altwegg R, et al.
OP38 Comparative efficacy of infliximab and vedolizumab after failure of a first anti-TNF in
patients with ulcerative colitis: a double-blind randomized controlled trial (EFFICACI). Journal
of Crohn’s and Colitis. 2025 Jan 1;19(Supplement_1):i74.
A few remarks for clarification :
1. Line 189: what is the difference between the number of sick leave and the number of sick days?
2. Line 250: Why are you so sure that missing data are unlikely in your study?
3. Line 300: Does it mean that 20% of patens receiving advanced therapies for induction are not
using them for maintenance? If so, are they switching to another advanced therapy?
4. The costs of UST are surprising to me. Given the low sample for UST, are you sure that these
data are representative?
Finally, with the data collected, would it be possible to define a  "path of least resistance", i.e an
"optimal sequence" that would optimize  the outcomes in most patients?
Overall a serious contribution to the topic.
Well done.
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: 23 Mar 2025
Reviewer:  Christian Agboton
Reviewer's report:
This is a an interesting paper addressing the notion of sequences of therapies in IBD, a topic that
is more and more prevalent given the large number of drugs available.
The authors managed to avoid the  main pitfalls in this type of analyses by having a precise
definition of sequences and applying propensity score matching  to ensure comparability across
the treatments.
The  results are largely in line with the recently published results, especially for vedolizumab.
The Discussion part is well done with a good summary of the evidence available so far.
The use of "inadequate response" is a novel approach to treatment evaluation.
I would just suggest adding :
- 1. Gros B, Ross H, Nwabueze M, Constantine-Cooke N, Derikx LAAP, Lyons M, et al. Long-
term outcomes and predictors of vedolizumab persistence in ulcerative colitis. Therap Adv
Gastroenterol. 2024;17:17562848241258372.
-2. Bouguen M.D.- PhD. G, Nachury M, Nancey S, Bouhnik Y, Bourreille A, Altwegg R, et al.
OP38 Comparative efficacy of infliximab and vedolizumab after failure of a first anti-TNF in
patients with ulcerative colitis: a double-blind randomized controlled trial (EFFICACI). Journal
of Crohn’s and Colitis. 2025 Jan 1;19(Supplement_1):i74.
A few remarks for clarification :
1. Line 189: what is the difference between the number of sick leave and the number of sick days?
2. Line 250: Why are you so sure that missing data are unlikely in your study?
3. Line 300: Does it mean that 20% of patens receiving advanced therapies for induction are not
using them for maintenance? If so, are they switching to another advanced therapy?
4. The costs of UST are surprising to me. Given the low sample for UST, are you sure that these
data are representative?
Finally, with the data collected, would it be possible to define a  "path of least resistance", i.e an
"optimal sequence" that would optimize  the outcomes in most patients?
Overall a serious contribution to the topic.
Well done.
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: 23 Mar 2025
Reviewer:  Christian Agboton
Reviewer's report:
This is a an interesting paper addressing the notion of sequences of therapies in IBD, a topic that
is more and more prevalent given the large number of drugs available.
The authors managed to avoid the  main pitfalls in this type of analyses by having a precise
definition of sequences and applying propensity score matching  to ensure comparability across
the treatments.
The  results are largely in line with the recently published results, especially for vedolizumab.
The Discussion part is well done with a good summary of the evidence available so far.
The use of "inadequate response" is a novel approach to treatment evaluation.
I would just suggest adding :
- 1. Gros B, Ross H, Nwabueze M, Constantine-Cooke N, Derikx LAAP, Lyons M, et al. Long-
term outcomes and predictors of vedolizumab persistence in ulcerative colitis. Therap Adv
Gastroenterol. 2024;17:17562848241258372.
-2. Bouguen M.D.- PhD. G, Nachury M, Nancey S, Bouhnik Y, Bourreille A, Altwegg R, et al.
OP38 Comparative efficacy of infliximab and vedolizumab after failure of a first anti-TNF in
patients with ulcerative colitis: a double-blind randomized controlled trial (EFFICACI). Journal
of Crohn’s and Colitis. 2025 Jan 1;19(Supplement_1):i74.
A few remarks for clarification :
1. Line 189: what is the difference between the number of sick leave and the number of sick days?
2. Line 250: Why are you so sure that missing data are unlikely in your study?
3. Line 300: Does it mean that 20% of patens receiving advanced therapies for induction are not
using them for maintenance? If so, are they switching to another advanced therapy?
4. The costs of UST are surprising to me. Given the low sample for UST, are you sure that these
data are representative?
Finally, with the data collected, would it be possible to define a  "path of least resistance", i.e an
"optimal sequence" that would optimize  the outcomes in most patients?
Overall a serious contribution to the topic.
Well done.
assistant