Title: Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in
patients with complex perianal fistulas in Crohn’s disease
Version: 8 Date: 07 Sep 2024
Reviewer's report:
A very relevant study aiming to clarify the long-term effectiveness of DVS against SoC, through
predictive modelling.
Disclosure: I reviewed a manuscript that had been previously reviewed by 5 reviewers, with
adequate replying from the authors.
Hence, I will present some comments, mostly (but not only) related to easiness of reading of
the text.
- P11,L235 – Table 2 – I would suggest that DVS and PBO/SoC would figure in a left column
so that the number of pts in each treatment could be summed in a total column on the right side
of the table. This would help understand the pts populations as studies are to be merged.
- P12,L254 A short sentence on the most relevant differences between groups would help the
reader – for example, almost half of the pts in PREFACE had luminal active disease, which
contrasts to the ADMIRE pts.
- P12,L257 I agree with Rev.#1 that median, IQR would be preferable. However, authors replied
that p-value was calculated using mean, SD. Nevertheless, I think that presenting both in the
table makes it more difficult to read, so maybe one of these distribution measures could figure
in the caption below the table.
- P13,L265-266 – I cannot fully understand what authors mean or wish to convey, when they
state that patients that present both “less remission and relapse” are “more stable patients”…
Less remission rates, means more activity; less relapse rates, means more stability of remission.
Moreover, as previously stated, PREFACE pts have active luminal CD in almost half of the
patients. So, authors should explain better what they want the reader to learn from this data. The
same for the discussions section, P17, L364.
- P14, L295 – “shorter estimated time to CPC remission…” – shouldn´t this be “longer”?
- P15,L307-308 – Fig.3C and 3D display different long results; this should be addressed in the
text.
- FIG.3 – As 3A and 3B are related to time to remission and 3C and 3D are related to time to
relapse, I suggest their separation (e.g. 3C + 3D should be FIG. 4A. and 4B); as it is, the reader
may tend to compare FIG. 3A and 3B with 3C based on their visual similarity, which, of course,
makes no sense.
- P.17,L365 – Not sure if the ADMIRE-CD pts are really more refractory pts, in what PCF
is concern. They have more duration of disease and more immunosuppressive/biologic use
but they have achieved luminal remission, while a part of the other studies’ pts have not. If
a pt is refractory to IS/biologics both in luminal- and PCF-CD, can he be considered more
refractory? Of course this would depend on the previous treatments and other variables…so I
am not comfortable with this sentence.
Title: Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in
patients with complex perianal fistulas in Crohn’s disease
Version: 8 Date: 07 Sep 2024
Reviewer's report:
A very relevant study aiming to clarify the long-term effectiveness of DVS against SoC, through
predictive modelling.
Disclosure: I reviewed a manuscript that had been previously reviewed by 5 reviewers, with
adequate replying from the authors.
Hence, I will present some comments, mostly (but not only) related to easiness of reading of
the text.
- P11,L235 – Table 2 – I would suggest that DVS and PBO/SoC would figure in a left column
so that the number of pts in each treatment could be summed in a total column on the right side
of the table. This would help understand the pts populations as studies are to be merged.
- P12,L254 A short sentence on the most relevant differences between groups would help the
reader – for example, almost half of the pts in PREFACE had luminal active disease, which
contrasts to the ADMIRE pts.
- P12,L257 I agree with Rev.#1 that median, IQR would be preferable. However, authors replied
that p-value was calculated using mean, SD. Nevertheless, I think that presenting both in the
table makes it more difficult to read, so maybe one of these distribution measures could figure
in the caption below the table.
- P13,L265-266 – I cannot fully understand what authors mean or wish to convey, when they
state that patients that present both “less remission and relapse” are “more stable patients”…
Less remission rates, means more activity; less relapse rates, means more stability of remission.
Moreover, as previously stated, PREFACE pts have active luminal CD in almost half of the
patients. So, authors should explain better what they want the reader to learn from this data. The
same for the discussions section, P17, L364.
- P14, L295 – “shorter estimated time to CPC remission…” – shouldn´t this be “longer”?
- P15,L307-308 – Fig.3C and 3D display different long results; this should be addressed in the
text.
- FIG.3 – As 3A and 3B are related to time to remission and 3C and 3D are related to time to
relapse, I suggest their separation (e.g. 3C + 3D should be FIG. 4A. and 4B); as it is, the reader
may tend to compare FIG. 3A and 3B with 3C based on their visual similarity, which, of course,
makes no sense.
- P.17,L365 – Not sure if the ADMIRE-CD pts are really more refractory pts, in what PCF
is concern. They have more duration of disease and more immunosuppressive/biologic use
but they have achieved luminal remission, while a part of the other studies’ pts have not. If
a pt is refractory to IS/biologics both in luminal- and PCF-CD, can he be considered more
refractory? Of course this would depend on the previous treatments and other variables…so I
am not comfortable with this sentence.
Please review this paper.
user
Title: Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in
patients with complex perianal fistulas in Crohn’s disease
Version: 8 Date: 07 Sep 2024
Reviewer's report:
A very relevant study aiming to clarify the long-term effectiveness of DVS against SoC, through
predictive modelling.
Disclosure: I reviewed a manuscript that had been previously reviewed by 5 reviewers, with
adequate replying from the authors.
Hence, I will present some comments, mostly (but not only) related to easiness of reading of
the text.
- P11,L235 – Table 2 – I would suggest that DVS and PBO/SoC would figure in a left column
so that the number of pts in each treatment could be summed in a total column on the right side
of the table. This would help understand the pts populations as studies are to be merged.
- P12,L254 A short sentence on the most relevant differences between groups would help the
reader – for example, almost half of the pts in PREFACE had luminal active disease, which
contrasts to the ADMIRE pts.
- P12,L257 I agree with Rev.#1 that median, IQR would be preferable. However, authors replied
that p-value was calculated using mean, SD. Nevertheless, I think that presenting both in the
table makes it more difficult to read, so maybe one of these distribution measures could figure
in the caption below the table.
- P13,L265-266 – I cannot fully understand what authors mean or wish to convey, when they
state that patients that present both “less remission and relapse” are “more stable patients”…
Less remission rates, means more activity; less relapse rates, means more stability of remission.
Moreover, as previously stated, PREFACE pts have active luminal CD in almost half of the
patients. So, authors should explain better what they want the reader to learn from this data. The
same for the discussions section, P17, L364.
- P14, L295 – “shorter estimated time to CPC remission…” – shouldn´t this be “longer”?
- P15,L307-308 – Fig.3C and 3D display different long results; this should be addressed in the
text.
- FIG.3 – As 3A and 3B are related to time to remission and 3C and 3D are related to time to
relapse, I suggest their separation (e.g. 3C + 3D should be FIG. 4A. and 4B); as it is, the reader
may tend to compare FIG. 3A and 3B with 3C based on their visual similarity, which, of course,
makes no sense.
- P.17,L365 – Not sure if the ADMIRE-CD pts are really more refractory pts, in what PCF
is concern. They have more duration of disease and more immunosuppressive/biologic use
but they have achieved luminal remission, while a part of the other studies’ pts have not. If
a pt is refractory to IS/biologics both in luminal- and PCF-CD, can he be considered more
refractory? Of course this would depend on the previous treatments and other variables…so I
am not comfortable with this sentence.
assistant