Reviewer ’s report  
 
Title: Inflammatory Bowel Disease (IBD) Pharmacotherapy and the Risk of Serious Infection:  
A Systematic Review and Network Meta -Analysis  
 
Version: 0 Date: 20 Dec 2016  
 
Reviewer: Jan Preiss  
 
Reviewer's report:  
 
In their manuscript the authors Chelle Wheat et al. try to elucidate the relative potency of 
different immunosuppressive drugs to cause serious infections. They use indirect treatment 
comparison for this. The scientific question is important and original. The manuscript is well 
written. The methods section is exhaustive and the  authors describe how they dealt with the 
question of inconsistency. The results too, are exhaustive. Strengths and weaknesses of the 
manuscript are clearly stated. Unfortunately the authors interpretation of the results might be 
questionable.  
The authors are not able to show a statistically significant difference between different 
treatments. The confidence intervals almost all include clinically significant differences. Not 
finding a difference between different drugs might as well just be a type II error . The wording in 
the manuscript suggests though, that this study was able to show equivalence of the risk for 
serious infections. Therefore the part "conclusion" in the abstract, the second paragraph in the 
discussion as well as the conclusion of the artic le should probably be rephrased.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
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 manuscript:  
 
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 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 shar es 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 rec eived 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 interest s 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.  
 
Yes, I have received reimbursements and fees from several pharmaceutical companies that may 
gain or lose financially from the publication: Takeda, Falk, MSD, Abbvie, Ferring, Pfizer  
 
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 manus cript 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://cr eativecommons.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: Inflammatory Bowel Disease (IBD) Pharmacotherapy and the Risk of Serious Infection:  
A Systematic Review and Network Meta -Analysis  
 
Version: 0 Date: 20 Dec 2016  
 
Reviewer: Jan Preiss  
 
Reviewer's report:  
 
In their manuscript the authors Chelle Wheat et al. try to elucidate the relative potency of 
different immunosuppressive drugs to cause serious infections. They use indirect treatment 
comparison for this. The scientific question is important and original. The manuscript is well 
written. The methods section is exhaustive and the  authors describe how they dealt with the 
question of inconsistency. The results too, are exhaustive. Strengths and weaknesses of the 
manuscript are clearly stated. Unfortunately the authors interpretation of the results might be 
questionable.  
The authors are not able to show a statistically significant difference between different 
treatments. The confidence intervals almost all include clinically significant differences. Not 
finding a difference between different drugs might as well just be a type II error . The wording in 
the manuscript suggests though, that this study was able to show equivalence of the risk for 
serious infections. Therefore the part "conclusion" in the abstract, the second paragraph in the 
discussion as well as the conclusion of the artic le should probably be rephrased.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
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 manuscript:  
 
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 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 shar es 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 rec eived 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 interest s 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.  
 
Yes, I have received reimbursements and fees from several pharmaceutical companies that may 
gain or lose financially from the publication: Takeda, Falk, MSD, Abbvie, Ferring, Pfizer  
 
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 manus cript 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://cr eativecommons.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: Inflammatory Bowel Disease (IBD) Pharmacotherapy and the Risk of Serious Infection:  
A Systematic Review and Network Meta -Analysis  
 
Version: 0 Date: 20 Dec 2016  
 
Reviewer: Jan Preiss  
 
Reviewer's report:  
 
In their manuscript the authors Chelle Wheat et al. try to elucidate the relative potency of 
different immunosuppressive drugs to cause serious infections. They use indirect treatment 
comparison for this. The scientific question is important and original. The manuscript is well 
written. The methods section is exhaustive and the  authors describe how they dealt with the 
question of inconsistency. The results too, are exhaustive. Strengths and weaknesses of the 
manuscript are clearly stated. Unfortunately the authors interpretation of the results might be 
questionable.  
The authors are not able to show a statistically significant difference between different 
treatments. The confidence intervals almost all include clinically significant differences. Not 
finding a difference between different drugs might as well just be a type II error . The wording in 
the manuscript suggests though, that this study was able to show equivalence of the risk for 
serious infections. Therefore the part "conclusion" in the abstract, the second paragraph in the 
discussion as well as the conclusion of the artic le should probably be rephrased.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
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 manuscript:  
 
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 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 shar es 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 rec eived 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 interest s 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.  
 
Yes, I have received reimbursements and fees from several pharmaceutical companies that may 
gain or lose financially from the publication: Takeda, Falk, MSD, Abbvie, Ferring, Pfizer  
 
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 manus cript 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://cr eativecommons.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