Reviewer ’s report  
 
Title: Real l ife results in using 5 -ASA for maintaining mild to moderate UC patients in Japan, a 
multi -center study; OPTIMUM Study  
 
Version: 0 Date: 11 Dec 2016  
 
Reviewer: Byong Duk Ye  
 
Reviewer' s report:  
 
The authors investigated real -life treatment pattern with oral 5 -ASA products for 4,677 Japanese 
patients with ulcerative colitis (UC) and evaluated the remission maintenance rates up to 52 
weeks. They also evaluated the remission maintenance rates according to 5 -ASA products and 
dosages. As a result, the remission maintenance rates at week 52 were not significantly different 
by various produ cts, dosage and frequency. The maintaining remission for 12 months or longer 
after induction therapy was shown to reduce recurrence risk thereafter. The strength of this study 
is the large number of patients enrolled and the reflection of real life practic e. However, the 
following points are needed to be elucidated.  
1. Substantial proportions of patients were also given topical 5 -ASA, probiotics, 
immunomodulators, anti -TNFs, or tacrolimus. Clinical symptoms can be significantly 
influenced by concomitant medication. Therefore, remission maintenance rates in the study 
subjects cannot be attributed to oral 5 -ASA alone. Therefore, the efficacy of oral 5 -ASA 
should be analyzed for patients who were managed with 5 -ASA alone.  
2. Results of endoscopic evaluation were not presented. In some proportion of patients, 
endoscopic e valuation might have been performed at 26 and/or 52 weeks. In substantial 
proportion of UC patients, endoscopic inflammation persists despite clinical remission and 
control of endoscopic inflammation is being emphasized recently. Results of subgroup 
analys is of subjects who were given endoscopic evaluation are needed to be presented.  
3. The definition or criteria for the followings is not clearly presented; remission, clinical 
course (first onset type, relapse -remitting type, and chronic continuous type), and 
complications.  
4. Definition of drinking habit and smoking habit is also unclear. Number of days of drinking 
per week without alcohol amount does not seem to be accurate. Classifying smoking habit as 
yes or no, without considering amount and duration  of smoking is not appropriate, either.  
5. How was pUCDAI evaluated? Was any defined written case report form or web -based case 
report form used ?      
6. Adverse events related with 5 -ASA were not presented.  
 
Are the methods 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.  
 
No 
 
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 manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing 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 gai n 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 fu ture?  
 
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 for patents relating to the content o f 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 authors and, if the manuscript is ac cepted 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://creativecommo ns.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: Real l ife results in using 5 -ASA for maintaining mild to moderate UC patients in Japan, a 
multi -center study; OPTIMUM Study  
 
Version: 0 Date: 11 Dec 2016  
 
Reviewer: Byong Duk Ye  
 
Reviewer' s report:  
 
The authors investigated real -life treatment pattern with oral 5 -ASA products for 4,677 Japanese 
patients with ulcerative colitis (UC) and evaluated the remission maintenance rates up to 52 
weeks. They also evaluated the remission maintenance rates according to 5 -ASA products and 
dosages. As a result, the remission maintenance rates at week 52 were not significantly different 
by various produ cts, dosage and frequency. The maintaining remission for 12 months or longer 
after induction therapy was shown to reduce recurrence risk thereafter. The strength of this study 
is the large number of patients enrolled and the reflection of real life practic e. However, the 
following points are needed to be elucidated.  
1. Substantial proportions of patients were also given topical 5 -ASA, probiotics, 
immunomodulators, anti -TNFs, or tacrolimus. Clinical symptoms can be significantly 
influenced by concomitant medication. Therefore, remission maintenance rates in the study 
subjects cannot be attributed to oral 5 -ASA alone. Therefore, the efficacy of oral 5 -ASA 
should be analyzed for patients who were managed with 5 -ASA alone.  
2. Results of endoscopic evaluation were not presented. In some proportion of patients, 
endoscopic e valuation might have been performed at 26 and/or 52 weeks. In substantial 
proportion of UC patients, endoscopic inflammation persists despite clinical remission and 
control of endoscopic inflammation is being emphasized recently. Results of subgroup 
analys is of subjects who were given endoscopic evaluation are needed to be presented.  
3. The definition or criteria for the followings is not clearly presented; remission, clinical 
course (first onset type, relapse -remitting type, and chronic continuous type), and 
complications.  
4. Definition of drinking habit and smoking habit is also unclear. Number of days of drinking 
per week without alcohol amount does not seem to be accurate. Classifying smoking habit as 
yes or no, without considering amount and duration  of smoking is not appropriate, either.  
5. How was pUCDAI evaluated? Was any defined written case report form or web -based case 
report form used ?      
6. Adverse events related with 5 -ASA were not presented.  
 
Are the methods 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.  
 
No 
 
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 manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing 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 gai n 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 fu ture?  
 
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 for patents relating to the content o f 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 authors and, if the manuscript is ac cepted 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://creativecommo ns.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: Real l ife results in using 5 -ASA for maintaining mild to moderate UC patients in Japan, a 
multi -center study; OPTIMUM Study  
 
Version: 0 Date: 11 Dec 2016  
 
Reviewer: Byong Duk Ye  
 
Reviewer' s report:  
 
The authors investigated real -life treatment pattern with oral 5 -ASA products for 4,677 Japanese 
patients with ulcerative colitis (UC) and evaluated the remission maintenance rates up to 52 
weeks. They also evaluated the remission maintenance rates according to 5 -ASA products and 
dosages. As a result, the remission maintenance rates at week 52 were not significantly different 
by various produ cts, dosage and frequency. The maintaining remission for 12 months or longer 
after induction therapy was shown to reduce recurrence risk thereafter. The strength of this study 
is the large number of patients enrolled and the reflection of real life practic e. However, the 
following points are needed to be elucidated.  
1. Substantial proportions of patients were also given topical 5 -ASA, probiotics, 
immunomodulators, anti -TNFs, or tacrolimus. Clinical symptoms can be significantly 
influenced by concomitant medication. Therefore, remission maintenance rates in the study 
subjects cannot be attributed to oral 5 -ASA alone. Therefore, the efficacy of oral 5 -ASA 
should be analyzed for patients who were managed with 5 -ASA alone.  
2. Results of endoscopic evaluation were not presented. In some proportion of patients, 
endoscopic e valuation might have been performed at 26 and/or 52 weeks. In substantial 
proportion of UC patients, endoscopic inflammation persists despite clinical remission and 
control of endoscopic inflammation is being emphasized recently. Results of subgroup 
analys is of subjects who were given endoscopic evaluation are needed to be presented.  
3. The definition or criteria for the followings is not clearly presented; remission, clinical 
course (first onset type, relapse -remitting type, and chronic continuous type), and 
complications.  
4. Definition of drinking habit and smoking habit is also unclear. Number of days of drinking 
per week without alcohol amount does not seem to be accurate. Classifying smoking habit as 
yes or no, without considering amount and duration  of smoking is not appropriate, either.  
5. How was pUCDAI evaluated? Was any defined written case report form or web -based case 
report form used ?      
6. Adverse events related with 5 -ASA were not presented.  
 
Are the methods 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.  
 
No 
 
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 manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing 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 gai n 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 fu ture?  
 
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 for patents relating to the content o f 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 authors and, if the manuscript is ac cepted 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://creativecommo ns.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