Review for 10.1186/s12876-025-04065-w (2025)

Title: Infliximab for Patients with Moderate to Severely Active Ulcerative Colitis: An Updated
Meta-Analysis of Randomized Controlled Trials
Version: 3 Date: 27 May 2025
Reviewer's report:
I have carefully reviewed your updated meta-analysis concerning the efficacy and safety
of infliximab (IFX) in patients with moderate-to-severe active ulcerative colitis (UC). Your
study is timely and addresses a critical clinical question; however, several methodological and
interpretive issues must be addressed before the manuscript can be considered for publication
in a high-impact journal.
General Assessment
Your meta-analysis includes 20 RCTs with a total of 2,350 patients, and it rigorously explores
short-term and long-term clinical outcomes. While the general structure is adequate, the
manuscript would benefit from more robust methodological transparency, refinement in result
interpretation, and enhanced critical discussion.
Abstract and Keywords
The abstract is clear but exceeds 250 words and should be refined for conciseness.
Keywords are relevant, but consider including: “Meta-analysis,” “TNF-alpha inhibitor,” and
“Evidence-Based Practice” for broader indexing.
Introduction
The background effectively introduces UC and the rationale for using IFX.
However, the introduction lacks a critical synthesis of existing meta-analyses or systematic
reviews. I recommend adding a comparative paragraph addressing what knowledge gap this
updated meta-analysis fills.
Methods
Search Strategy & Study Selection:
The databases used are comprehensive, but the search string and Boolean operators are not
provided. For reproducibility, include this in the appendix or as supplementary material.
PRISMA 2020 checklist is included, but adherence is only partial. Flow diagram Figure 1 should
be re-evaluated for clarity and completeness, especially in distinguishing included/excluded full-
text articles.
Eligibility Criteria:
The rationale for including various comparators (placebo, steroids, 5-ASA,
immunosuppressants) should be better justified in the context of clinical heterogeneity.
Data Extraction and Risk of Bias:
It is stated that two reviewers extracted data independently, but it is not confirmed whether they
were blinded. This is a crucial detail for reducing selection and detection bias.
Risk of bias assessment must explicitly report the use of Cochrane RoB 2 tool domains rather
than general statements. Currently, this section lacks depth.
Statistical Analysis:
The use of relative risk (RR) and 95% CI is appropriate, and heterogeneity is assessed via I².
However:
The thresholds for I² interpretation are not mentioned.
Random vs fixed effects models usage criteria should be detailed.
Publication bias detection using contour-enhanced funnel plots is cited, but the Egger’s
regression test is not mentioned, which would strengthen the assessment.
Results
The results are presented in structured fashion, with effect sizes and confidence intervals.
However, several improvements are needed:
Forest plots should include study weights and heterogeneity stats per outcome.
Subgroup analyses (e.g., based on IFX dose or comparator type) are mentioned but not
sufficiently interpreted. Were there any statistically significant differences?
The figures require standardized resolution and uniform format (e.g., TIF and JPG formats are
inconsistently used).
Figures 3, 5, and 6 are difficult to interpret visually and need higher contrast and labeling.
Supplementary Table 1 lacks clarity in some cells, particularly those related to adverse events.
Discussion
The discussion reiterates the findings but does not offer deep mechanistic or pharmacodynamic
interpretation of IFX effects.
The limitations section should be expanded to include:
Possible publication bias due to language restrictions.
Heterogeneity in comparator treatments and follow-up durations.
The lack of individual patient data (IPD), which limits the ability to explore moderators of
treatment effect.
Recommendations for future research are vague. I suggest detailing prospective real-world
cohort studies or head-to-head IFX comparisons.
Figures and Tables
As noted, standardization and resolution improvements are necessary.
Table 2 and Supplementary Table 1 need footnotes explaining abbreviations and statistical
indicators.
Consider relocating forest plots to supplementary material if space is limited, but retain
publication bias and subgroup analyses in the main text.
Conclusions
The conclusion is justified by the data but must be tempered to reflect the heterogeneity and
quality limitations.
Avoid strong endorsements of clinical implementation based solely on pooled RCT data without
discussing long-term safety, cost-effectiveness, or comparative effectiveness versus newer
biologics.
Additional Recommendations
Ensure consistency of terminology (e.g., “clinical remission” vs. “disease remission”).
Ensure all references are up-to-date and properly formatted in Vancouver style.
Consider submitting the full dataset and code (e.g., RevMan, Stata, or R script) as supplementary
materials, promoting reproducibility.
Given that the Polishing Certificate is attached, the language is mostly fluent, but further
improvements can be made in transitions and scientific tone in some sections.
Final Verdict
Major Revisions Required. The study is of high potential scientific value, but it requires
substantial improvements in the methodological reporting, critical discussion, and visual
presentation of data to meet the standards of rigorous evidence synthesis.