Reviewer ’s report  
 
Title: Optimizing biologic treatment in IBD: objective measures, but when, how and how often?  
 
Version: 0 Date: 11 Oct 2015  
 
Reviewer: Jan Preiss  
 
Reviewer's report:  
The authors Shomron Ben -Horin et al. submitted a fine and exh austive review about the use of 
laboratory and imaging markers in assessing patients with inflammatory  bowel diseases. They 
cover the area by lo oking at the following situations:  
- before and during induction phase  
- after induction  
- at loss of response  
- before and after stopping therapy  
- role of endoscopy for optimizing treatment  
 
I only have very few comments:  
1. In the section "before and dur ing induction phase" the authors g ive an exhaustive review 
on the role of CRP. They should also discuss the role of fecal calprotect ion and 
abdominal ultrasoun d in this situation. In countries where ultrasound is routinely used by 
gastroenterologists thems elves at the bedside, e.g. Italy, Switzerland, or Germany, this 
techno logy proved to be excellent for verifying inflammation without relying on more 
invasive or c omplex imaging modalities, i.e. endoscopy or MRI, especially in terminal 
ileitis, where calpro tectin is often false negative.  
 
2. At the end of the section about therapeutic drug monitoring the a uthors give a caveat 
about this method: optimal thresholds need to be established. The authors mention 
themselves that "patients with adequate drug elvels a nd active inflammation  will 
USUALLY respond better to switch to another class of drugs". Relying to heavily on 
these algorithms might miss a few patients in whom a higher drug level will lead to 
clinical response  therby unnecessarily foregoing one of the f ew drugs that exist for 
Crohn's disease. I feel the auth ors need to discuss this caveat too. 
 
3. In discussing the role of mucosal healing the authors will have  to mention the POCER 
study and the role of endoscopy in optimizing post -operative treatment.  
 
 
conc lusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of c ompeting interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the a uthors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
Reviewer ’s report  
 
Title: Optimizing biologic treatment in IBD: objective measures, but when, how and how often?  
 
Version: 0 Date: 11 Oct 2015  
 
Reviewer: Jan Preiss  
 
Reviewer's report:  
The authors Shomron Ben -Horin et al. submitted a fine and exh austive review about the use of 
laboratory and imaging markers in assessing patients with inflammatory  bowel diseases. They 
cover the area by lo oking at the following situations:  
- before and during induction phase  
- after induction  
- at loss of response  
- before and after stopping therapy  
- role of endoscopy for optimizing treatment  
 
I only have very few comments:  
1. In the section "before and dur ing induction phase" the authors g ive an exhaustive review 
on the role of CRP. They should also discuss the role of fecal calprotect ion and 
abdominal ultrasoun d in this situation. In countries where ultrasound is routinely used by 
gastroenterologists thems elves at the bedside, e.g. Italy, Switzerland, or Germany, this 
techno logy proved to be excellent for verifying inflammation without relying on more 
invasive or c omplex imaging modalities, i.e. endoscopy or MRI, especially in terminal 
ileitis, where calpro tectin is often false negative.  
 
2. At the end of the section about therapeutic drug monitoring the a uthors give a caveat 
about this method: optimal thresholds need to be established. The authors mention 
themselves that "patients with adequate drug elvels a nd active inflammation  will 
USUALLY respond better to switch to another class of drugs". Relying to heavily on 
these algorithms might miss a few patients in whom a higher drug level will lead to 
clinical response  therby unnecessarily foregoing one of the f ew drugs that exist for 
Crohn's disease. I feel the auth ors need to discuss this caveat too. 
 
3. In discussing the role of mucosal healing the authors will have  to mention the POCER 
study and the role of endoscopy in optimizing post -operative treatment.  
 
 
conc lusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of c ompeting interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the a uthors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Optimizing biologic treatment in IBD: objective measures, but when, how and how often?  
 
Version: 0 Date: 11 Oct 2015  
 
Reviewer: Jan Preiss  
 
Reviewer's report:  
The authors Shomron Ben -Horin et al. submitted a fine and exh austive review about the use of 
laboratory and imaging markers in assessing patients with inflammatory  bowel diseases. They 
cover the area by lo oking at the following situations:  
- before and during induction phase  
- after induction  
- at loss of response  
- before and after stopping therapy  
- role of endoscopy for optimizing treatment  
 
I only have very few comments:  
1. In the section "before and dur ing induction phase" the authors g ive an exhaustive review 
on the role of CRP. They should also discuss the role of fecal calprotect ion and 
abdominal ultrasoun d in this situation. In countries where ultrasound is routinely used by 
gastroenterologists thems elves at the bedside, e.g. Italy, Switzerland, or Germany, this 
techno logy proved to be excellent for verifying inflammation without relying on more 
invasive or c omplex imaging modalities, i.e. endoscopy or MRI, especially in terminal 
ileitis, where calpro tectin is often false negative.  
 
2. At the end of the section about therapeutic drug monitoring the a uthors give a caveat 
about this method: optimal thresholds need to be established. The authors mention 
themselves that "patients with adequate drug elvels a nd active inflammation  will 
USUALLY respond better to switch to another class of drugs". Relying to heavily on 
these algorithms might miss a few patients in whom a higher drug level will lead to 
clinical response  therby unnecessarily foregoing one of the f ew drugs that exist for 
Crohn's disease. I feel the auth ors need to discuss this caveat too. 
 
3. In discussing the role of mucosal healing the authors will have  to mention the POCER 
study and the role of endoscopy in optimizing post -operative treatment.  
 
 
conc lusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of c ompeting interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the a uthors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
assistant