Reviewer ’s report  
 
Title: Therapeutic preferences and outcomes in newly diagnosed patien ts with Crohn's disease in  
the biological era in Hungary. A nationwide study based on the National Health Insurance Fund  
database  
 
Version: 0 Date: 02 Nov 2017  
 
Reviewer: Julajak Limsri vilai 
 
Reviewer's report:  
 
The authors showed a nationwide trend of IBD treatment in Hungary in which 
immunomodulators and biologics have been increasingly used after 2009. The results also 
showed that the rate of hospitalization, but not surgery, decreased with more biologics and 
immunomodulators use. This finding supports the importance of early use of biologics and 
immunomodulators. Please find my comments below.  
 
 
 
1. The authors stated that early introduction of immunomodulators and biologics may be 
associated with improved o utcomes such as lower risk of surgery and hospitalization in 
previous studies, therefore the aim of this study was to investigate how these changing 
paradigms affect clinical outcomes. In this study, the authors categorized the patients 
according to the ma ximum treatment received at 3 years after the initial diagnosis. What 
is the logic behind categorizing the patients at 3 years period? Could the authors have 
tried to categorize the patients at a different time point, such as 1 year, which would 
probably b etter reflects the effect of early introduction of biologics/immunomodulators?  
 
 
2. In this observational study, the authors said that maximal treatment steps can be regarded 
as proxy severity markers in patients with IBD. However, to investigate the effect of 
biologics treatment, I would suggest doing more analyses by comparing the outcomes 
between patients with the same disease severity who did and did not receive biologics by 
matching the patients using propensity score. Factors possibly associated with di sease 
severity such as age, gender, hemoglobin level and complicated disease behaviors e.g. 
stricture/fistula/perianal or upper tract involvement should also be integrated into the 
propensity score. Another way to highlight the effect of biologics on the o utcomes is to 
use Cox proportional hazards regression adjusted for factors that might be related to the 
disease severity.  
 
 
 
 
 
 
Are the me thods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursemen ts, 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 org anization 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 o f 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 authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under a n 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 name d 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: Therapeutic preferences and outcomes in newly diagnosed patien ts with Crohn's disease in  
the biological era in Hungary. A nationwide study based on the National Health Insurance Fund  
database  
 
Version: 0 Date: 02 Nov 2017  
 
Reviewer: Julajak Limsri vilai 
 
Reviewer's report:  
 
The authors showed a nationwide trend of IBD treatment in Hungary in which 
immunomodulators and biologics have been increasingly used after 2009. The results also 
showed that the rate of hospitalization, but not surgery, decreased with more biologics and 
immunomodulators use. This finding supports the importance of early use of biologics and 
immunomodulators. Please find my comments below.  
 
 
 
1. The authors stated that early introduction of immunomodulators and biologics may be 
associated with improved o utcomes such as lower risk of surgery and hospitalization in 
previous studies, therefore the aim of this study was to investigate how these changing 
paradigms affect clinical outcomes. In this study, the authors categorized the patients 
according to the ma ximum treatment received at 3 years after the initial diagnosis. What 
is the logic behind categorizing the patients at 3 years period? Could the authors have 
tried to categorize the patients at a different time point, such as 1 year, which would 
probably b etter reflects the effect of early introduction of biologics/immunomodulators?  
 
 
2. In this observational study, the authors said that maximal treatment steps can be regarded 
as proxy severity markers in patients with IBD. However, to investigate the effect of 
biologics treatment, I would suggest doing more analyses by comparing the outcomes 
between patients with the same disease severity who did and did not receive biologics by 
matching the patients using propensity score. Factors possibly associated with di sease 
severity such as age, gender, hemoglobin level and complicated disease behaviors e.g. 
stricture/fistula/perianal or upper tract involvement should also be integrated into the 
propensity score. Another way to highlight the effect of biologics on the o utcomes is to 
use Cox proportional hazards regression adjusted for factors that might be related to the 
disease severity.  
 
 
 
 
 
 
Are the me thods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursemen ts, 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 org anization 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 o f 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 authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under a n 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 name d 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: Therapeutic preferences and outcomes in newly diagnosed patien ts with Crohn's disease in  
the biological era in Hungary. A nationwide study based on the National Health Insurance Fund  
database  
 
Version: 0 Date: 02 Nov 2017  
 
Reviewer: Julajak Limsri vilai 
 
Reviewer's report:  
 
The authors showed a nationwide trend of IBD treatment in Hungary in which 
immunomodulators and biologics have been increasingly used after 2009. The results also 
showed that the rate of hospitalization, but not surgery, decreased with more biologics and 
immunomodulators use. This finding supports the importance of early use of biologics and 
immunomodulators. Please find my comments below.  
 
 
 
1. The authors stated that early introduction of immunomodulators and biologics may be 
associated with improved o utcomes such as lower risk of surgery and hospitalization in 
previous studies, therefore the aim of this study was to investigate how these changing 
paradigms affect clinical outcomes. In this study, the authors categorized the patients 
according to the ma ximum treatment received at 3 years after the initial diagnosis. What 
is the logic behind categorizing the patients at 3 years period? Could the authors have 
tried to categorize the patients at a different time point, such as 1 year, which would 
probably b etter reflects the effect of early introduction of biologics/immunomodulators?  
 
 
2. In this observational study, the authors said that maximal treatment steps can be regarded 
as proxy severity markers in patients with IBD. However, to investigate the effect of 
biologics treatment, I would suggest doing more analyses by comparing the outcomes 
between patients with the same disease severity who did and did not receive biologics by 
matching the patients using propensity score. Factors possibly associated with di sease 
severity such as age, gender, hemoglobin level and complicated disease behaviors e.g. 
stricture/fistula/perianal or upper tract involvement should also be integrated into the 
propensity score. Another way to highlight the effect of biologics on the o utcomes is to 
use Cox proportional hazards regression adjusted for factors that might be related to the 
disease severity.  
 
 
 
 
 
 
Are the me thods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursemen ts, 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 org anization 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 o f 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 authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under a n 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 name d 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