Title: Indicators of suboptimal response to anti-tumor necrosis factor therapy in patients from
China with inflammatory bowel disease: Results from the EXPLORE study
Version: 5 Date: 12 May 2021
Reviewer's report:
Dear Sir/ Madam,
Many thanks for allowing me to review this paper titled "Indicators of suboptimal response
to anti-tumor necrosis factor therapy in patients from China with inflammatory bowel disease:
Results from the EXPLORE study" by Dr. J Li and colleagues. This paper discussed parameters
linked to sub-optimal response to anti-TNFs in China and analyzes factors associated with sub-
optimal response to IFX, which is a very relevant clinical outcome in everyday clinical practice
in IBD.
I believe that your paper cannot be accepted in its current form, but may be considered for
acceptance in BMC Gastroenterology provided you adequately address and correct the issues
below.
Comments regarding the quality of this paper and issues that require revision and correction are
listed below
Major comments:
1. an important focus of your paper should be factors associated with sub-optimal response.
Therefore I recommend moving supp figure 2 and possibly also supp figure 1 to the main paper
2. Please add a table comparing epidemiological and clinical factors between responders and
sub-optimal responders (factors as described in the comparison between UC and CD)
3. For this comparison (between responders and non-responders) I'd recommend adding separate
analyses for primary non-responders and SLOR
4. In the discussion (page 19 lines 332-341): this paragraph is NOT related to any of the results
presented in this paper and therefore irrelevant. Please remove.
5. I could not understand how often was Anti-TNF therapy presented here offered in an episodic
form or always as maintenance therapy following standard induction. Please clarify.
6. In table 1: please present the data on disease location in a more standard way (Montreal
classification system): L1, L2, L3, Upper GI as modifiers and perianal disease as modifier as
well.
7. Please add the definitions of severity indices to the methods section (not as legends to the
table) and provide references. clinical response definition should also added in the methods
Minor comments:
1. concomitant use non-biologic immunosuppressants was unusually low. Please discuss this
in the discussion section especially in reference to rates of administration of combo therapy in
other places in Asia and Europe/US
2. What happened to UC patients experiencing sub-optimal response to IFX (a very common
outcome in your cohort..)? Was surgery (total proctocolectomy) offered then? Please describe
the practice in the 10 centers in China
3. did any center use therapeutic drug monitoring of IFX  and antibodies to IFX in clinical
decision making?
4. Was methotrexate used in CD patients? please make the distinction between thiopurines and
methotrexate in table 1.
5. Page 16 line 245: please rephrase: ...use of combination therapy was protective from
suboptimal response..
Many thanks once again for allowing me to review this paper. I hope you find my comments
constructive.
Best wishes,
Title: Indicators of suboptimal response to anti-tumor necrosis factor therapy in patients from
China with inflammatory bowel disease: Results from the EXPLORE study
Version: 5 Date: 12 May 2021
Reviewer's report:
Dear Sir/ Madam,
Many thanks for allowing me to review this paper titled "Indicators of suboptimal response
to anti-tumor necrosis factor therapy in patients from China with inflammatory bowel disease:
Results from the EXPLORE study" by Dr. J Li and colleagues. This paper discussed parameters
linked to sub-optimal response to anti-TNFs in China and analyzes factors associated with sub-
optimal response to IFX, which is a very relevant clinical outcome in everyday clinical practice
in IBD.
I believe that your paper cannot be accepted in its current form, but may be considered for
acceptance in BMC Gastroenterology provided you adequately address and correct the issues
below.
Comments regarding the quality of this paper and issues that require revision and correction are
listed below
Major comments:
1. an important focus of your paper should be factors associated with sub-optimal response.
Therefore I recommend moving supp figure 2 and possibly also supp figure 1 to the main paper
2. Please add a table comparing epidemiological and clinical factors between responders and
sub-optimal responders (factors as described in the comparison between UC and CD)
3. For this comparison (between responders and non-responders) I'd recommend adding separate
analyses for primary non-responders and SLOR
4. In the discussion (page 19 lines 332-341): this paragraph is NOT related to any of the results
presented in this paper and therefore irrelevant. Please remove.
5. I could not understand how often was Anti-TNF therapy presented here offered in an episodic
form or always as maintenance therapy following standard induction. Please clarify.
6. In table 1: please present the data on disease location in a more standard way (Montreal
classification system): L1, L2, L3, Upper GI as modifiers and perianal disease as modifier as
well.
7. Please add the definitions of severity indices to the methods section (not as legends to the
table) and provide references. clinical response definition should also added in the methods
Minor comments:
1. concomitant use non-biologic immunosuppressants was unusually low. Please discuss this
in the discussion section especially in reference to rates of administration of combo therapy in
other places in Asia and Europe/US
2. What happened to UC patients experiencing sub-optimal response to IFX (a very common
outcome in your cohort..)? Was surgery (total proctocolectomy) offered then? Please describe
the practice in the 10 centers in China
3. did any center use therapeutic drug monitoring of IFX  and antibodies to IFX in clinical
decision making?
4. Was methotrexate used in CD patients? please make the distinction between thiopurines and
methotrexate in table 1.
5. Page 16 line 245: please rephrase: ...use of combination therapy was protective from
suboptimal response..
Many thanks once again for allowing me to review this paper. I hope you find my comments
constructive.
Best wishes,
Please review this paper.
user
Title: Indicators of suboptimal response to anti-tumor necrosis factor therapy in patients from
China with inflammatory bowel disease: Results from the EXPLORE study
Version: 5 Date: 12 May 2021
Reviewer's report:
Dear Sir/ Madam,
Many thanks for allowing me to review this paper titled "Indicators of suboptimal response
to anti-tumor necrosis factor therapy in patients from China with inflammatory bowel disease:
Results from the EXPLORE study" by Dr. J Li and colleagues. This paper discussed parameters
linked to sub-optimal response to anti-TNFs in China and analyzes factors associated with sub-
optimal response to IFX, which is a very relevant clinical outcome in everyday clinical practice
in IBD.
I believe that your paper cannot be accepted in its current form, but may be considered for
acceptance in BMC Gastroenterology provided you adequately address and correct the issues
below.
Comments regarding the quality of this paper and issues that require revision and correction are
listed below
Major comments:
1. an important focus of your paper should be factors associated with sub-optimal response.
Therefore I recommend moving supp figure 2 and possibly also supp figure 1 to the main paper
2. Please add a table comparing epidemiological and clinical factors between responders and
sub-optimal responders (factors as described in the comparison between UC and CD)
3. For this comparison (between responders and non-responders) I'd recommend adding separate
analyses for primary non-responders and SLOR
4. In the discussion (page 19 lines 332-341): this paragraph is NOT related to any of the results
presented in this paper and therefore irrelevant. Please remove.
5. I could not understand how often was Anti-TNF therapy presented here offered in an episodic
form or always as maintenance therapy following standard induction. Please clarify.
6. In table 1: please present the data on disease location in a more standard way (Montreal
classification system): L1, L2, L3, Upper GI as modifiers and perianal disease as modifier as
well.
7. Please add the definitions of severity indices to the methods section (not as legends to the
table) and provide references. clinical response definition should also added in the methods
Minor comments:
1. concomitant use non-biologic immunosuppressants was unusually low. Please discuss this
in the discussion section especially in reference to rates of administration of combo therapy in
other places in Asia and Europe/US
2. What happened to UC patients experiencing sub-optimal response to IFX (a very common
outcome in your cohort..)? Was surgery (total proctocolectomy) offered then? Please describe
the practice in the 10 centers in China
3. did any center use therapeutic drug monitoring of IFX  and antibodies to IFX in clinical
decision making?
4. Was methotrexate used in CD patients? please make the distinction between thiopurines and
methotrexate in table 1.
5. Page 16 line 245: please rephrase: ...use of combination therapy was protective from
suboptimal response..
Many thanks once again for allowing me to review this paper. I hope you find my comments
constructive.
Best wishes,
assistant