Reviewer ’s report  
 
Title: Exclusive enteral nutrition induction with concomitant early thiopurine use is effective in 
maintaining steroid free remission in a Southeast Asian cohort of children with Crohn's Disease  
 
Version: 1 Date: 11 May 2018  
 
Reviewer: Andrew Day  
 
Reviewer's report:  
 
This MS focuses on the role of EEN and medical maintenance therapies in a cohort of children 
with CD  
 
Specific Comments  
1. The authors comment that 5 -ASA drugs were used in all patients. What was the protocol that 
lead to early or late  introduction of AZATHIOPRINE? Was this reflecting a standard 
protocol? please detail  
 
2. Was maintenance enteral nutrition also utilised in these patients after the period of EEN? 
How did this affect the outcomes?  
 
3. The term steroid free remission was not  used in the ABSTRACT  
 
4. The INTRODUCTION is too long and should be shortened and focused more  
 
5. The authors explain the term CD twice  
 
6. Has should be have (line 36, page 4)  
 
7. In the methods, the authors state that remission is PCDAI less than or equal to 10, whilst 
relapse is greater than and equal to 10. This suggests that 10 is both remission and relapse. 
Suggest correct the remission to be < 10  
 
8. The patient group included children from age 3 years: did all these toddlers also undergo 
MRE as stated earlier?  
 
9. Some of the descriptive details (of the patient group) could be included in the Table without 
duplication in the text. Some of the results section could be revised to be more clear.  
 
10. In the response to EEN section, the authors first give details of the group who did not 
respond, although this was not clear on first reading. It may be more clear to give the details 
of the respondents first and then the others  
 
11. The authors note th at 11 of the EAZ group were in remission at 12 months. Does this mean 
that these children had remained in remission for the full 12 months or that this number 
happened to be in remission at the 12 month time point. This is hard to be clear  
 
12. Were other t herapies utilised in the 12 month period?  
 
13. Did growth reflect better control over 6 and 12 months? Did vitamin d status influence 
outcomes?  
 
14. There are a number of errors of English language use - these should all be corrected  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work inclu de the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions 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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing inter ests, 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 c ontent of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for 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 n o 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 authors and, if the manuscript is accepted for publication, my named report  
including any a ttachments 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 comment s 
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: Exclusive enteral nutrition induction with concomitant early thiopurine use is effective in 
maintaining steroid free remission in a Southeast Asian cohort of children with Crohn's Disease  
 
Version: 1 Date: 11 May 2018  
 
Reviewer: Andrew Day  
 
Reviewer's report:  
 
This MS focuses on the role of EEN and medical maintenance therapies in a cohort of children 
with CD  
 
Specific Comments  
1. The authors comment that 5 -ASA drugs were used in all patients. What was the protocol that 
lead to early or late  introduction of AZATHIOPRINE? Was this reflecting a standard 
protocol? please detail  
 
2. Was maintenance enteral nutrition also utilised in these patients after the period of EEN? 
How did this affect the outcomes?  
 
3. The term steroid free remission was not  used in the ABSTRACT  
 
4. The INTRODUCTION is too long and should be shortened and focused more  
 
5. The authors explain the term CD twice  
 
6. Has should be have (line 36, page 4)  
 
7. In the methods, the authors state that remission is PCDAI less than or equal to 10, whilst 
relapse is greater than and equal to 10. This suggests that 10 is both remission and relapse. 
Suggest correct the remission to be < 10  
 
8. The patient group included children from age 3 years: did all these toddlers also undergo 
MRE as stated earlier?  
 
9. Some of the descriptive details (of the patient group) could be included in the Table without 
duplication in the text. Some of the results section could be revised to be more clear.  
 
10. In the response to EEN section, the authors first give details of the group who did not 
respond, although this was not clear on first reading. It may be more clear to give the details 
of the respondents first and then the others  
 
11. The authors note th at 11 of the EAZ group were in remission at 12 months. Does this mean 
that these children had remained in remission for the full 12 months or that this number 
happened to be in remission at the 12 month time point. This is hard to be clear  
 
12. Were other t herapies utilised in the 12 month period?  
 
13. Did growth reflect better control over 6 and 12 months? Did vitamin d status influence 
outcomes?  
 
14. There are a number of errors of English language use - these should all be corrected  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work inclu de the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions 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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing inter ests, 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 c ontent of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for 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 n o 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 authors and, if the manuscript is accepted for publication, my named report  
including any a ttachments 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 comment s 
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: Exclusive enteral nutrition induction with concomitant early thiopurine use is effective in 
maintaining steroid free remission in a Southeast Asian cohort of children with Crohn's Disease  
 
Version: 1 Date: 11 May 2018  
 
Reviewer: Andrew Day  
 
Reviewer's report:  
 
This MS focuses on the role of EEN and medical maintenance therapies in a cohort of children 
with CD  
 
Specific Comments  
1. The authors comment that 5 -ASA drugs were used in all patients. What was the protocol that 
lead to early or late  introduction of AZATHIOPRINE? Was this reflecting a standard 
protocol? please detail  
 
2. Was maintenance enteral nutrition also utilised in these patients after the period of EEN? 
How did this affect the outcomes?  
 
3. The term steroid free remission was not  used in the ABSTRACT  
 
4. The INTRODUCTION is too long and should be shortened and focused more  
 
5. The authors explain the term CD twice  
 
6. Has should be have (line 36, page 4)  
 
7. In the methods, the authors state that remission is PCDAI less than or equal to 10, whilst 
relapse is greater than and equal to 10. This suggests that 10 is both remission and relapse. 
Suggest correct the remission to be < 10  
 
8. The patient group included children from age 3 years: did all these toddlers also undergo 
MRE as stated earlier?  
 
9. Some of the descriptive details (of the patient group) could be included in the Table without 
duplication in the text. Some of the results section could be revised to be more clear.  
 
10. In the response to EEN section, the authors first give details of the group who did not 
respond, although this was not clear on first reading. It may be more clear to give the details 
of the respondents first and then the others  
 
11. The authors note th at 11 of the EAZ group were in remission at 12 months. Does this mean 
that these children had remained in remission for the full 12 months or that this number 
happened to be in remission at the 12 month time point. This is hard to be clear  
 
12. Were other t herapies utilised in the 12 month period?  
 
13. Did growth reflect better control over 6 and 12 months? Did vitamin d status influence 
outcomes?  
 
14. There are a number of errors of English language use - these should all be corrected  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work inclu de the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions 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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing inter ests, 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 c ontent of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for 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 n o 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 authors and, if the manuscript is accepted for publication, my named report  
including any a ttachments 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 comment s 
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