Title: Infliximab for Patients with Moderate to Severely Active Ulcerative Colitis: An Updated
Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 15 May 2025
Reviewer's report:
Dear Authors,
You are doing excellent work, and this manuscript reflects a great deal of effort and thoughtful
research. The study is promising and contributes meaningfully to the field. However, there are a
few important points that require further clarification and revision to enhance the overall quality
and impact of the manuscript.
Line 52: While the background effectively introduces ulcerative colitis (UC) and the role of
infliximab (IFX), it would benefit from a clearer articulation of the knowledge gap. Specifically,
explain more explicitly what previous studies have lacked (e.g., prospective design, randomized
control, long-term outcomes), and how this study addresses those deficiencies.
Line 65: To enhance Background section add the following reference:  Zahraa A. Abdulrazaq,
ZA., Al-Ouqaili, MTS.,  Talib, NM. 2024. The impact of circulating 25-hydroxyvitamin D
and vitamin D receptor variation on leukemia-lymphoma outcome: Molecular and cytogenetic
study, Saudi Journal of Biological Sciences, Volume 31, Issue 1. http://doi.org/10.1016/
j.sjbs.2023.103882.
Line 73: Though it could be more clearly supported, the discussion of the issue around the use of
IFX is significant. Give a brief explanation of the nature of the debate, such as immunogenicity,
cost-effectiveness, disparate efficacy in different patient subgroups, or variability in treatment
response.
Line 93: The outcomes (e.g., short-term clinical response, long-term clinical remission,
endoscopic mucosal healing) are listed, but definitions and timeframes are not specified. Specify
how “short-term” and “long-term” are operationally defined (e.g., weeks or months), and
whether standardized criteria (e.g., Mayo score thresholds) were used.
Line 97: Explain why only randomized controlled trials (RCTs) were included. While this
enhances internal validity, some high-quality non-RCTs may also provide useful insights,
especially if RCT data are limited. If RCTs are essential due to your analytic framework (e.g.,
meta-analysis), state this explicitly.
Line 164: While the authors mention that 285 articles were excluded after full-text review, it
would improve clarity and transparency to briefly categorize the main reasons for exclusion
(e.g., non-RCTs, insufficient outcome data, inappropriate population). This information could
be included as a supplementary table or summarized in the main text.
Line 175: The dosage categories for infliximab are somewhat unclear due to overlapping trial
references (e.g., trials [33, 36] appear in both 10 mg/kg and 20 mg/kg groups). Please verify
and clarify the dosing information for each trial to avoid confusion. Consider grouping doses
consistently and explaining any rationale for dose variations.
Line 183: Instead of stating “The study characteristics are listed in Supplementary Table 1,”
briefly summarize key study features in the main text to improve the flow and inform the reader
without needing to consult supplementary material.
Line 202:Rather than "mild," the reported I2 values (55.8% and 66.4%) show moderate
heterogeneity. Briefly explain how you understand heterogeneity and provide evidence
to support your selection of the random-effects model. Investigating possible sources of
heterogeneity through sensitivity or subgroup analyses would help improve the analysis.
Line 202:The p-values for heterogeneity (P=0.003 and P=0.011) suggest statistically significant
heterogeneity, which should be acknowledged explicitly. Consider including Tau² values to
provide further insight into between-study variance.
Line 214:The I² values (62.4% and 65.6%) reflect moderate heterogeneity, not “mild.” Please
clarify this and discuss potential reasons for heterogeneity or consider subgroup/sensitivity
analyses.
Line 217:In the last sentence, you mention “long-term clinical response rate,” but this section is
about clinical remission. Please verify and correct this inconsistency.
Line 333:To enhance discussion section add the following reference: • Abdulrazaq ZA, Al-
Ouqaili, MTS, Talib NM. Association Between Circulating 25-Hydroxy Vitamin D Receptor
and Molecular Response in Multiple Myeloma. Pak J Biol Sci. 2023 Aug;26(9):472-481. http://
doi.org/10.3923/pjbs.2023.472.481
Line 448: Conclusion should be objective with further perspective or should add at least a few
sentences about future study/future perspective of it
Title: Infliximab for Patients with Moderate to Severely Active Ulcerative Colitis: An Updated
Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 15 May 2025
Reviewer's report:
Dear Authors,
You are doing excellent work, and this manuscript reflects a great deal of effort and thoughtful
research. The study is promising and contributes meaningfully to the field. However, there are a
few important points that require further clarification and revision to enhance the overall quality
and impact of the manuscript.
Line 52: While the background effectively introduces ulcerative colitis (UC) and the role of
infliximab (IFX), it would benefit from a clearer articulation of the knowledge gap. Specifically,
explain more explicitly what previous studies have lacked (e.g., prospective design, randomized
control, long-term outcomes), and how this study addresses those deficiencies.
Line 65: To enhance Background section add the following reference:  Zahraa A. Abdulrazaq,
ZA., Al-Ouqaili, MTS.,  Talib, NM. 2024. The impact of circulating 25-hydroxyvitamin D
and vitamin D receptor variation on leukemia-lymphoma outcome: Molecular and cytogenetic
study, Saudi Journal of Biological Sciences, Volume 31, Issue 1. http://doi.org/10.1016/
j.sjbs.2023.103882.
Line 73: Though it could be more clearly supported, the discussion of the issue around the use of
IFX is significant. Give a brief explanation of the nature of the debate, such as immunogenicity,
cost-effectiveness, disparate efficacy in different patient subgroups, or variability in treatment
response.
Line 93: The outcomes (e.g., short-term clinical response, long-term clinical remission,
endoscopic mucosal healing) are listed, but definitions and timeframes are not specified. Specify
how “short-term” and “long-term” are operationally defined (e.g., weeks or months), and
whether standardized criteria (e.g., Mayo score thresholds) were used.
Line 97: Explain why only randomized controlled trials (RCTs) were included. While this
enhances internal validity, some high-quality non-RCTs may also provide useful insights,
especially if RCT data are limited. If RCTs are essential due to your analytic framework (e.g.,
meta-analysis), state this explicitly.
Line 164: While the authors mention that 285 articles were excluded after full-text review, it
would improve clarity and transparency to briefly categorize the main reasons for exclusion
(e.g., non-RCTs, insufficient outcome data, inappropriate population). This information could
be included as a supplementary table or summarized in the main text.
Line 175: The dosage categories for infliximab are somewhat unclear due to overlapping trial
references (e.g., trials [33, 36] appear in both 10 mg/kg and 20 mg/kg groups). Please verify
and clarify the dosing information for each trial to avoid confusion. Consider grouping doses
consistently and explaining any rationale for dose variations.
Line 183: Instead of stating “The study characteristics are listed in Supplementary Table 1,”
briefly summarize key study features in the main text to improve the flow and inform the reader
without needing to consult supplementary material.
Line 202:Rather than "mild," the reported I2 values (55.8% and 66.4%) show moderate
heterogeneity. Briefly explain how you understand heterogeneity and provide evidence
to support your selection of the random-effects model. Investigating possible sources of
heterogeneity through sensitivity or subgroup analyses would help improve the analysis.
Line 202:The p-values for heterogeneity (P=0.003 and P=0.011) suggest statistically significant
heterogeneity, which should be acknowledged explicitly. Consider including Tau² values to
provide further insight into between-study variance.
Line 214:The I² values (62.4% and 65.6%) reflect moderate heterogeneity, not “mild.” Please
clarify this and discuss potential reasons for heterogeneity or consider subgroup/sensitivity
analyses.
Line 217:In the last sentence, you mention “long-term clinical response rate,” but this section is
about clinical remission. Please verify and correct this inconsistency.
Line 333:To enhance discussion section add the following reference: • Abdulrazaq ZA, Al-
Ouqaili, MTS, Talib NM. Association Between Circulating 25-Hydroxy Vitamin D Receptor
and Molecular Response in Multiple Myeloma. Pak J Biol Sci. 2023 Aug;26(9):472-481. http://
doi.org/10.3923/pjbs.2023.472.481
Line 448: Conclusion should be objective with further perspective or should add at least a few
sentences about future study/future perspective of it
Please review this paper.
user
Title: Infliximab for Patients with Moderate to Severely Active Ulcerative Colitis: An Updated
Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 15 May 2025
Reviewer's report:
Dear Authors,
You are doing excellent work, and this manuscript reflects a great deal of effort and thoughtful
research. The study is promising and contributes meaningfully to the field. However, there are a
few important points that require further clarification and revision to enhance the overall quality
and impact of the manuscript.
Line 52: While the background effectively introduces ulcerative colitis (UC) and the role of
infliximab (IFX), it would benefit from a clearer articulation of the knowledge gap. Specifically,
explain more explicitly what previous studies have lacked (e.g., prospective design, randomized
control, long-term outcomes), and how this study addresses those deficiencies.
Line 65: To enhance Background section add the following reference:  Zahraa A. Abdulrazaq,
ZA., Al-Ouqaili, MTS.,  Talib, NM. 2024. The impact of circulating 25-hydroxyvitamin D
and vitamin D receptor variation on leukemia-lymphoma outcome: Molecular and cytogenetic
study, Saudi Journal of Biological Sciences, Volume 31, Issue 1. http://doi.org/10.1016/
j.sjbs.2023.103882.
Line 73: Though it could be more clearly supported, the discussion of the issue around the use of
IFX is significant. Give a brief explanation of the nature of the debate, such as immunogenicity,
cost-effectiveness, disparate efficacy in different patient subgroups, or variability in treatment
response.
Line 93: The outcomes (e.g., short-term clinical response, long-term clinical remission,
endoscopic mucosal healing) are listed, but definitions and timeframes are not specified. Specify
how “short-term” and “long-term” are operationally defined (e.g., weeks or months), and
whether standardized criteria (e.g., Mayo score thresholds) were used.
Line 97: Explain why only randomized controlled trials (RCTs) were included. While this
enhances internal validity, some high-quality non-RCTs may also provide useful insights,
especially if RCT data are limited. If RCTs are essential due to your analytic framework (e.g.,
meta-analysis), state this explicitly.
Line 164: While the authors mention that 285 articles were excluded after full-text review, it
would improve clarity and transparency to briefly categorize the main reasons for exclusion
(e.g., non-RCTs, insufficient outcome data, inappropriate population). This information could
be included as a supplementary table or summarized in the main text.
Line 175: The dosage categories for infliximab are somewhat unclear due to overlapping trial
references (e.g., trials [33, 36] appear in both 10 mg/kg and 20 mg/kg groups). Please verify
and clarify the dosing information for each trial to avoid confusion. Consider grouping doses
consistently and explaining any rationale for dose variations.
Line 183: Instead of stating “The study characteristics are listed in Supplementary Table 1,”
briefly summarize key study features in the main text to improve the flow and inform the reader
without needing to consult supplementary material.
Line 202:Rather than "mild," the reported I2 values (55.8% and 66.4%) show moderate
heterogeneity. Briefly explain how you understand heterogeneity and provide evidence
to support your selection of the random-effects model. Investigating possible sources of
heterogeneity through sensitivity or subgroup analyses would help improve the analysis.
Line 202:The p-values for heterogeneity (P=0.003 and P=0.011) suggest statistically significant
heterogeneity, which should be acknowledged explicitly. Consider including Tau² values to
provide further insight into between-study variance.
Line 214:The I² values (62.4% and 65.6%) reflect moderate heterogeneity, not “mild.” Please
clarify this and discuss potential reasons for heterogeneity or consider subgroup/sensitivity
analyses.
Line 217:In the last sentence, you mention “long-term clinical response rate,” but this section is
about clinical remission. Please verify and correct this inconsistency.
Line 333:To enhance discussion section add the following reference: • Abdulrazaq ZA, Al-
Ouqaili, MTS, Talib NM. Association Between Circulating 25-Hydroxy Vitamin D Receptor
and Molecular Response in Multiple Myeloma. Pak J Biol Sci. 2023 Aug;26(9):472-481. http://
doi.org/10.3923/pjbs.2023.472.481
Line 448: Conclusion should be objective with further perspective or should add at least a few
sentences about future study/future perspective of it
assistant