Review for 10.1186/s12876-017-0654-1 (2017)

Reviewer ’s report  
 
Title:  Drug persistence and need  for dose intensification to adalimumab therapy; the importance 
of therapeutic drug monitoring in inflammatory bowel diseases  
 
Version: 0 Date: 06 Jun 2017 
 
Reviewer:  Brain  Bressler  
 
Reviewer’s report:  
 
The clinical state of the patients when TDM was ordered is not clear.  The authors mention an 
objective of the study was to determine whether TDM can predict LOR.  If indeed that was 
looked at I woul d assume TDM was performed when patients where in remission before they 
flared.  If TDM was done at time of LOR then an association could be looked for as opposed to 
the value of TDM to predict clinical course.  
 
If the hypothesis remains that ADAs are drug  neutralizing, why does approx. 10% of the cohort 
have 'normal' TL with 'high' ADAs?  
 
As these patients were prospectively followed, further evaluation of them after TDM was 
collected and a clinical decision/change of therapy was done would be helpful  
 
Specify why the cut -off values were chosen for the anti -drug antibodies. I am assuming they are 
the limit of the ELISA test they were using? I've seen the lower limit in one other paper, but not 
200ng/mL.  
 
Line 98: I'm not sure what the word "Twit" means i n this context  
 
Line 196 -197: for association between TL and ADA positivity, considering that the p -value 
>0.05 and CI crosses 1 for the OR, the authors should state "though not statistically significant, 
there may be an trend towards…"  
 
I am not sure why the Cox regression analysis was performed in the final results, as I do not see 
estimated HR for the possible significant variables. Would a multivariate logistic regression on 
the significant variable be useful in terms of confirming the relevance of each  of the variables 
found significant on what I assume is univariate analysis?  
 
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 nec essary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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  
 
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