Title: Effectiveness and safety of adalimumab in patients with intestinal Behçet’s disease: a
real-world prospective observational study in South Korea
Version: 4 Date: 26 Sep 2023
Reviewer's report:
Jongwook Yu et al. reported Effectiveness and safety of adalimumab in patients with intestinal
Behçet’s disease as a real-world prospective observational study in South Korea.
I have the following comments for the authors:
In my opinion, the safety profile, adverse events, and adverse drug reactions should be
considered secondary endpoints. Adalimumab's efficacy should be the primary endpoint. The
long-term safety of adalimumab has been well established in numerous studies, including meta-
analyses with long-term follow-up in autoimmune diseases, rheumatologic diseases, and IBD.
Thus, assessing the safety of this agent in a very small cohort is less compelling. On the other
hand, the efficacy of adalimumab has not been thoroughly studied.
Page 6, Line 124-131: 4. Assessment of safety: The primary objective was to identify adverse
events and collect information about safety profiles, while the secondary objective was adverse
drug reactions. These sentences might be confusing in relation to the primary endpoint (safety)
and secondary endpoint (effectiveness). Additionally, please define serious adverse events,
serious drug reactions, and unexpected adverse events in this section.
Page 8, Line 176: Nine patients were excluded from the analysis (5 due to inappropriate doses).
Please clarify what constitutes inappropriate doses. Also, 1 patient was excluded due to non-
administration of adalimumab. I believe this patient, who did not receive adalimumab, should
not be counted as an included case from the outset. Therefore, it should be 58 patients, not 59.
Page 8, Line 181-182: Four patients were excluded due to researcher decision and other reasons.
Please clarify what "researcher decision" and "other reasons" entail. It is not very clear. Were
any patients discontinued from ADAL due to adverse effects/reactions?
Page 8, Line 184: The mean disease duration was reported as 57.1±55.1 years (ranging from a
minimum of 0 to a maximum of 216.0 years). Please review the statistics as it is not possible
to have a disease duration of 216 years.
Page 10, Line 3: "(Clinical outcomes by univariable and multivariable analyses)" should be
deleted.
Page 10: The normal value of CRP should be provided somewhere.
Page 12, Line 249:
• Studies were performed at Week 28 and Week 56. This can be deleted, as it was mentioned
in the methods section.
• "At Week 56, 28.6% (2/7) achieved complete mucosal healing with the same percentages in
reduction and no change" is unclear. Please clarify what "same percentages in reduction and no
change" means. Also, "marked reduction" needs to be defined.
Discussion: Please discuss recently published articles and meta-analyses, such as:
• Zhang M, Liu J, Liu T, Han W, Bai X, Ruan G, Lv H, Shu H, Li Y, Li J, Tan B, Zheng W, Xu
H, Zheng W, Yang H, Qian J. The efficacy and safety of anti-tumor necrosis factor agents in the
treatment of intestinal Behcet's disease, a systematic review and meta-analysis. J Gastroenterol
Hepatol. 2022 Apr;37(4):608-619. doi: 10.1111/jgh.15754. Epub 2022 Jan 3. PMID: 34894004.
• van der Houwen TB, Humer B, Missotten TO, Thiadens AAHJ, van Hagen PM, van Laar JAM.
Long-term data on efficacy and safety of adalimumab in Behçet's disease. Clin Immunol. 2023
Feb;247:109242. doi: 10.1016/j.clim.2023.109242. Epub 2023 Jan 28. PMID: 36717068.
Table 1: Height and body weight are not necessary. Smoking history can be presented as a
percentage of smokers. Some concomitant medications, such as opioids, analgesics, and anti-
TB drugs, can be removed and do not need to be presented.
Table 2 / Table 3 / Table 4: There are too many variables. Please select only the most important
variables. Multiple variables should not be included in the logistic regression analysis. For
example, previous treatment history, previous medical history, and concomitant medications are
not specific variables. Authors should include only variables that are related to each outcome.
I hope the comment can improved the quality of the manuscript
Thank you
Title: Effectiveness and safety of adalimumab in patients with intestinal Behçet’s disease: a
real-world prospective observational study in South Korea
Version: 4 Date: 26 Sep 2023
Reviewer's report:
Jongwook Yu et al. reported Effectiveness and safety of adalimumab in patients with intestinal
Behçet’s disease as a real-world prospective observational study in South Korea.
I have the following comments for the authors:
In my opinion, the safety profile, adverse events, and adverse drug reactions should be
considered secondary endpoints. Adalimumab's efficacy should be the primary endpoint. The
long-term safety of adalimumab has been well established in numerous studies, including meta-
analyses with long-term follow-up in autoimmune diseases, rheumatologic diseases, and IBD.
Thus, assessing the safety of this agent in a very small cohort is less compelling. On the other
hand, the efficacy of adalimumab has not been thoroughly studied.
Page 6, Line 124-131: 4. Assessment of safety: The primary objective was to identify adverse
events and collect information about safety profiles, while the secondary objective was adverse
drug reactions. These sentences might be confusing in relation to the primary endpoint (safety)
and secondary endpoint (effectiveness). Additionally, please define serious adverse events,
serious drug reactions, and unexpected adverse events in this section.
Page 8, Line 176: Nine patients were excluded from the analysis (5 due to inappropriate doses).
Please clarify what constitutes inappropriate doses. Also, 1 patient was excluded due to non-
administration of adalimumab. I believe this patient, who did not receive adalimumab, should
not be counted as an included case from the outset. Therefore, it should be 58 patients, not 59.
Page 8, Line 181-182: Four patients were excluded due to researcher decision and other reasons.
Please clarify what "researcher decision" and "other reasons" entail. It is not very clear. Were
any patients discontinued from ADAL due to adverse effects/reactions?
Page 8, Line 184: The mean disease duration was reported as 57.1±55.1 years (ranging from a
minimum of 0 to a maximum of 216.0 years). Please review the statistics as it is not possible
to have a disease duration of 216 years.
Page 10, Line 3: "(Clinical outcomes by univariable and multivariable analyses)" should be
deleted.
Page 10: The normal value of CRP should be provided somewhere.
Page 12, Line 249:
• Studies were performed at Week 28 and Week 56. This can be deleted, as it was mentioned
in the methods section.
• "At Week 56, 28.6% (2/7) achieved complete mucosal healing with the same percentages in
reduction and no change" is unclear. Please clarify what "same percentages in reduction and no
change" means. Also, "marked reduction" needs to be defined.
Discussion: Please discuss recently published articles and meta-analyses, such as:
• Zhang M, Liu J, Liu T, Han W, Bai X, Ruan G, Lv H, Shu H, Li Y, Li J, Tan B, Zheng W, Xu
H, Zheng W, Yang H, Qian J. The efficacy and safety of anti-tumor necrosis factor agents in the
treatment of intestinal Behcet's disease, a systematic review and meta-analysis. J Gastroenterol
Hepatol. 2022 Apr;37(4):608-619. doi: 10.1111/jgh.15754. Epub 2022 Jan 3. PMID: 34894004.
• van der Houwen TB, Humer B, Missotten TO, Thiadens AAHJ, van Hagen PM, van Laar JAM.
Long-term data on efficacy and safety of adalimumab in Behçet's disease. Clin Immunol. 2023
Feb;247:109242. doi: 10.1016/j.clim.2023.109242. Epub 2023 Jan 28. PMID: 36717068.
Table 1: Height and body weight are not necessary. Smoking history can be presented as a
percentage of smokers. Some concomitant medications, such as opioids, analgesics, and anti-
TB drugs, can be removed and do not need to be presented.
Table 2 / Table 3 / Table 4: There are too many variables. Please select only the most important
variables. Multiple variables should not be included in the logistic regression analysis. For
example, previous treatment history, previous medical history, and concomitant medications are
not specific variables. Authors should include only variables that are related to each outcome.
I hope the comment can improved the quality of the manuscript
Thank you
Please review this paper.
user
Title: Effectiveness and safety of adalimumab in patients with intestinal Behçet’s disease: a
real-world prospective observational study in South Korea
Version: 4 Date: 26 Sep 2023
Reviewer's report:
Jongwook Yu et al. reported Effectiveness and safety of adalimumab in patients with intestinal
Behçet’s disease as a real-world prospective observational study in South Korea.
I have the following comments for the authors:
In my opinion, the safety profile, adverse events, and adverse drug reactions should be
considered secondary endpoints. Adalimumab's efficacy should be the primary endpoint. The
long-term safety of adalimumab has been well established in numerous studies, including meta-
analyses with long-term follow-up in autoimmune diseases, rheumatologic diseases, and IBD.
Thus, assessing the safety of this agent in a very small cohort is less compelling. On the other
hand, the efficacy of adalimumab has not been thoroughly studied.
Page 6, Line 124-131: 4. Assessment of safety: The primary objective was to identify adverse
events and collect information about safety profiles, while the secondary objective was adverse
drug reactions. These sentences might be confusing in relation to the primary endpoint (safety)
and secondary endpoint (effectiveness). Additionally, please define serious adverse events,
serious drug reactions, and unexpected adverse events in this section.
Page 8, Line 176: Nine patients were excluded from the analysis (5 due to inappropriate doses).
Please clarify what constitutes inappropriate doses. Also, 1 patient was excluded due to non-
administration of adalimumab. I believe this patient, who did not receive adalimumab, should
not be counted as an included case from the outset. Therefore, it should be 58 patients, not 59.
Page 8, Line 181-182: Four patients were excluded due to researcher decision and other reasons.
Please clarify what "researcher decision" and "other reasons" entail. It is not very clear. Were
any patients discontinued from ADAL due to adverse effects/reactions?
Page 8, Line 184: The mean disease duration was reported as 57.1±55.1 years (ranging from a
minimum of 0 to a maximum of 216.0 years). Please review the statistics as it is not possible
to have a disease duration of 216 years.
Page 10, Line 3: "(Clinical outcomes by univariable and multivariable analyses)" should be
deleted.
Page 10: The normal value of CRP should be provided somewhere.
Page 12, Line 249:
• Studies were performed at Week 28 and Week 56. This can be deleted, as it was mentioned
in the methods section.
• "At Week 56, 28.6% (2/7) achieved complete mucosal healing with the same percentages in
reduction and no change" is unclear. Please clarify what "same percentages in reduction and no
change" means. Also, "marked reduction" needs to be defined.
Discussion: Please discuss recently published articles and meta-analyses, such as:
• Zhang M, Liu J, Liu T, Han W, Bai X, Ruan G, Lv H, Shu H, Li Y, Li J, Tan B, Zheng W, Xu
H, Zheng W, Yang H, Qian J. The efficacy and safety of anti-tumor necrosis factor agents in the
treatment of intestinal Behcet's disease, a systematic review and meta-analysis. J Gastroenterol
Hepatol. 2022 Apr;37(4):608-619. doi: 10.1111/jgh.15754. Epub 2022 Jan 3. PMID: 34894004.
• van der Houwen TB, Humer B, Missotten TO, Thiadens AAHJ, van Hagen PM, van Laar JAM.
Long-term data on efficacy and safety of adalimumab in Behçet's disease. Clin Immunol. 2023
Feb;247:109242. doi: 10.1016/j.clim.2023.109242. Epub 2023 Jan 28. PMID: 36717068.
Table 1: Height and body weight are not necessary. Smoking history can be presented as a
percentage of smokers. Some concomitant medications, such as opioids, analgesics, and anti-
TB drugs, can be removed and do not need to be presented.
Table 2 / Table 3 / Table 4: There are too many variables. Please select only the most important
variables. Multiple variables should not be included in the logistic regression analysis. For
example, previous treatment history, previous medical history, and concomitant medications are
not specific variables. Authors should include only variables that are related to each outcome.
I hope the comment can improved the quality of the manuscript
Thank you
assistant