Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 04 Sep 2021
Reviewer's report:
Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with
refractory Crohn’s disease: a Chinese Real-world study
Thank you for the opportunity to review this interesting study. This is the first report on UST in
CD PK from Chinese, therefore the work is important added value. The strength of the work is
prospective observation and multiple endpoints analyzed. In particular, the endoscopy read by
experts adds robustness. The limitation of the study is its relatively limited sample size of 19
pts, but this could be appropriately addressed – please see my comments of Results section.
Specific comments:
CONLUSIONS: please replace “weapon” with for example “option” or “drug”.
INTRODUCTION: please focus more on what is known about PK in UST CD, you can easily
convert 1st paragraph to just one sentence to shorten this part.
RESULTS: since you excluded 18 pts due to follow-up less than 16 weeks please consider to wait
for this pts to reach week 16/20 and include also these. This would much increase the validity
of your results as you would almost double the cohort i.e 19 +18= 37 pts. You also excluded 17
pts due to lack of data (endoscopy, trough levels, colecotomy) – these pts should be included, as
you can still use their data to calculate the endpoints for which you have the data – for example
pts with colectomy should be regarded as “no endoscopic remission, no clinical remission…”.
In pts without trough levels you can still calculate clinical, endoscopic remission etc. By adding
these pts you could further increase the amount of pts 19+18+17=54 – this would again increase
the validity of your work. Furthermore, this would decrease the possible bias of your work.
DISCUSSION
Be careful about your conclusion that UST trough concentration of 1.12 is the optimal one.
In fact this is only correlation that you observe. I would guess the higher concentration the
better. But yes, I agree that pts with concentrations lower than this should be considered for dose
optimization as otherwise the chance of remission is low. Here you could also refer in discussion
to recent paper where ustekinumab concentrations after dose optimization predicted mucosal
healing, but not those before (Hanzel EJGH 2021, Ustekinumab concentrations shortly after
escalation to monthly dosing may identify endoscopic remission in refractory Crohn's disease)
Fugure 4: why do use cutoff of ustekinumab of 4.5 (and the one you identified 1.12?)
Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 04 Sep 2021
Reviewer's report:
Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with
refractory Crohn’s disease: a Chinese Real-world study
Thank you for the opportunity to review this interesting study. This is the first report on UST in
CD PK from Chinese, therefore the work is important added value. The strength of the work is
prospective observation and multiple endpoints analyzed. In particular, the endoscopy read by
experts adds robustness. The limitation of the study is its relatively limited sample size of 19
pts, but this could be appropriately addressed – please see my comments of Results section.
Specific comments:
CONLUSIONS: please replace “weapon” with for example “option” or “drug”.
INTRODUCTION: please focus more on what is known about PK in UST CD, you can easily
convert 1st paragraph to just one sentence to shorten this part.
RESULTS: since you excluded 18 pts due to follow-up less than 16 weeks please consider to wait
for this pts to reach week 16/20 and include also these. This would much increase the validity
of your results as you would almost double the cohort i.e 19 +18= 37 pts. You also excluded 17
pts due to lack of data (endoscopy, trough levels, colecotomy) – these pts should be included, as
you can still use their data to calculate the endpoints for which you have the data – for example
pts with colectomy should be regarded as “no endoscopic remission, no clinical remission…”.
In pts without trough levels you can still calculate clinical, endoscopic remission etc. By adding
these pts you could further increase the amount of pts 19+18+17=54 – this would again increase
the validity of your work. Furthermore, this would decrease the possible bias of your work.
DISCUSSION
Be careful about your conclusion that UST trough concentration of 1.12 is the optimal one.
In fact this is only correlation that you observe. I would guess the higher concentration the
better. But yes, I agree that pts with concentrations lower than this should be considered for dose
optimization as otherwise the chance of remission is low. Here you could also refer in discussion
to recent paper where ustekinumab concentrations after dose optimization predicted mucosal
healing, but not those before (Hanzel EJGH 2021, Ustekinumab concentrations shortly after
escalation to monthly dosing may identify endoscopic remission in refractory Crohn's disease)
Fugure 4: why do use cutoff of ustekinumab of 4.5 (and the one you identified 1.12?)
Please review this paper.
user
Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 04 Sep 2021
Reviewer's report:
Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with
refractory Crohn’s disease: a Chinese Real-world study
Thank you for the opportunity to review this interesting study. This is the first report on UST in
CD PK from Chinese, therefore the work is important added value. The strength of the work is
prospective observation and multiple endpoints analyzed. In particular, the endoscopy read by
experts adds robustness. The limitation of the study is its relatively limited sample size of 19
pts, but this could be appropriately addressed – please see my comments of Results section.
Specific comments:
CONLUSIONS: please replace “weapon” with for example “option” or “drug”.
INTRODUCTION: please focus more on what is known about PK in UST CD, you can easily
convert 1st paragraph to just one sentence to shorten this part.
RESULTS: since you excluded 18 pts due to follow-up less than 16 weeks please consider to wait
for this pts to reach week 16/20 and include also these. This would much increase the validity
of your results as you would almost double the cohort i.e 19 +18= 37 pts. You also excluded 17
pts due to lack of data (endoscopy, trough levels, colecotomy) – these pts should be included, as
you can still use their data to calculate the endpoints for which you have the data – for example
pts with colectomy should be regarded as “no endoscopic remission, no clinical remission…”.
In pts without trough levels you can still calculate clinical, endoscopic remission etc. By adding
these pts you could further increase the amount of pts 19+18+17=54 – this would again increase
the validity of your work. Furthermore, this would decrease the possible bias of your work.
DISCUSSION
Be careful about your conclusion that UST trough concentration of 1.12 is the optimal one.
In fact this is only correlation that you observe. I would guess the higher concentration the
better. But yes, I agree that pts with concentrations lower than this should be considered for dose
optimization as otherwise the chance of remission is low. Here you could also refer in discussion
to recent paper where ustekinumab concentrations after dose optimization predicted mucosal
healing, but not those before (Hanzel EJGH 2021, Ustekinumab concentrations shortly after
escalation to monthly dosing may identify endoscopic remission in refractory Crohn's disease)
Fugure 4: why do use cutoff of ustekinumab of 4.5 (and the one you identified 1.12?)
assistant