Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 11 Aug 2021
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
- “CD patients”
Patients with CD
- Define what is mucosal healing in CD
- “UST showed ideal efficacy”
Ideal?
- Use the abbreviation in the whole text after the definition (for example for Crohn’s disease)
- Since this is a retrospective study, and you stated “All patients underwent endoscopy prior to
UST initiation and at week 16/20 after UST therapy (approximately the third administration of
UST)”: in your clinical practice that each patients undergo colonoscopy 4-5 months after the
start of a biologic? If this is an inclusion criterion, you have to modify the methods defining
inclusion and exclusion criteria
- Regarding the outcomes (endoscopic and clinical remission): how did you consider the patients
that stopped ustekinumab due to primary failure? How did you consider patients on steroid
therapy at the timepoint of the outcome assessment?
- SES-CD could be calculated in patients with a history of intestinal resection too
- How do you explain a so different ability to predict endoscopic remission respect to clinical
response of trough levels?
- “Therefore, a TDM based on trough concentration is the optimal strategy for patients with
poor response or loss of response to UST therapy.” “UST optimization based on TDM is of core
importance for patients who lose responses”
You can’t state this because you did not prove that a dose escalation of ustekinumab based on
trough levels improved the outcome and you did non analysed the setting of loss of response.
- “Therefore, when patients lose response to UST, therapeutic drug monitoring is of great
importance to ensure that UST treatment can be optimized before switching to other therapeutic
strategies.”
What about performing a dose escalation from 12 to 8 weeks without TDM but based on clinical
parameters?
- Are the results of the kits used in the various studies about trough levels of ustekinumab
comparable or every center must find a threshold according to the kit he uses?
Title: Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients
with refractory Crohn’s disease: a Chinese real-world study
Version: 0 Date: 11 Aug 2021
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
- “CD patients”
Patients with CD
- Define what is mucosal healing in CD
- “UST showed ideal efficacy”
Ideal?
- Use the abbreviation in the whole text after the definition (for example for Crohn’s disease)
- Since this is a retrospective study, and you stated “All patients underwent endoscopy prior to
UST initiation and at week 16/20 after UST therapy (approximately the third administration of
UST)”: in your clinical practice that each patients undergo colonoscopy 4-5 months after the
start of a biologic? If this is an inclusion criterion, you have to modify the methods defining
inclusion and exclusion criteria
- Regarding the outcomes (endoscopic and clinical remission): how did you consider the patients
that stopped ustekinumab due to primary failure? How did you consider patients on steroid
therapy at the timepoint of the outcome assessment?
- SES-CD could be calculated in patients with a history of intestinal resection too
- How do you explain a so different ability to predict endoscopic remission respect to clinical
response of trough levels?
- “Therefore, a TDM based on trough concentration is the optimal strategy for patients with
poor response or loss of response to UST therapy.” “UST optimization based on TDM is of core
importance for patients who lose responses”
You can’t state this because you did not prove that a dose escalation of ustekinumab based on
trough levels improved the outcome and you did non analysed the setting of loss of response.
- “Therefore, when patients lose response to UST, therapeutic drug monitoring is of great
importance to ensure that UST treatment can be optimized before switching to other therapeutic
strategies.”
What about performing a dose escalation from 12 to 8 weeks without TDM but based on clinical
parameters?
- Are the results of the kits used in the various studies about trough levels of ustekinumab
comparable or every center must find a threshold according to the kit he uses?
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: 11 Aug 2021
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
- “CD patients”
Patients with CD
- Define what is mucosal healing in CD
- “UST showed ideal efficacy”
Ideal?
- Use the abbreviation in the whole text after the definition (for example for Crohn’s disease)
- Since this is a retrospective study, and you stated “All patients underwent endoscopy prior to
UST initiation and at week 16/20 after UST therapy (approximately the third administration of
UST)”: in your clinical practice that each patients undergo colonoscopy 4-5 months after the
start of a biologic? If this is an inclusion criterion, you have to modify the methods defining
inclusion and exclusion criteria
- Regarding the outcomes (endoscopic and clinical remission): how did you consider the patients
that stopped ustekinumab due to primary failure? How did you consider patients on steroid
therapy at the timepoint of the outcome assessment?
- SES-CD could be calculated in patients with a history of intestinal resection too
- How do you explain a so different ability to predict endoscopic remission respect to clinical
response of trough levels?
- “Therefore, a TDM based on trough concentration is the optimal strategy for patients with
poor response or loss of response to UST therapy.” “UST optimization based on TDM is of core
importance for patients who lose responses”
You can’t state this because you did not prove that a dose escalation of ustekinumab based on
trough levels improved the outcome and you did non analysed the setting of loss of response.
- “Therefore, when patients lose response to UST, therapeutic drug monitoring is of great
importance to ensure that UST treatment can be optimized before switching to other therapeutic
strategies.”
What about performing a dose escalation from 12 to 8 weeks without TDM but based on clinical
parameters?
- Are the results of the kits used in the various studies about trough levels of ustekinumab
comparable or every center must find a threshold according to the kit he uses?
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