Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 5 Date: 28 Dec 2024
Reviewer's report:
The results presented in all Figures of the meta-analysis are inappropriate and cannot be
approved for the following reasons. The authors emphasize that this is the first meta-analysis
of mirikizumab; however, the purpose of a meta-analysis is to strengthen the evidence obtained
from individual clinical trials or to provide new insights. This meta-analysis is problematic
because it incorporates doses not used in clinical practice and appears to involve analyses that
were conducted arbitrarily to yield significant results. We hope that the authors will collect real-
world data on mirikizumab in the future and present them as a meta-analysis.
• Figure 3: Based on the regulatory situation in the FDA and Japan, I understand that mirikizumab
has been approved for induction therapy at 300 mg followed by maintenance therapy at 200 mg.
Conducting a meta-analysis on the efficacy of 50 mg, 200 mg, and 600 mg induction doses has
no clinical relevance.
• Figure 4: In Figure 4A, the risk ratio crosses 1, which likely prompted the sensitivity analysis
shown in Figure 4B. However, the rationale for excluding only the Sandborn 2022 study is not
provided. Furthermore, excluding studies such as Sandborn 2020 or D’Haens 2023 would likely
result in a risk ratio crossing 1. Therefore, Figure 4 must be considered arbitrary.
• Figures 5 and 6: As with Figure 3, combining results from trials using unapproved doses in a
meta-analysis provides no meaningful clinical impact.
• Figure 7: The same concerns raised for Figure 3 also apply here. Moreover, the weight of
D’Haens 2023 is 97.3%, which is unacceptable for a meta-analysis result.
• Figure 8: The weight of D’Haens 2023 is excessively high, making the meta-analysis results
unsuitable for adoption.
• Figure 9: The same concerns as those raised for Figure 3 apply here.
• Figures 10 and 11: These figures are inappropriate for the same reasons mentioned regarding
Figure 4.
• Figure 12: Similar to Figure 7, the weight of D’Haens 2023 is excessively high, making the
results unsuitable for inclusion in the meta-analysis.
Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 5 Date: 28 Dec 2024
Reviewer's report:
The results presented in all Figures of the meta-analysis are inappropriate and cannot be
approved for the following reasons. The authors emphasize that this is the first meta-analysis
of mirikizumab; however, the purpose of a meta-analysis is to strengthen the evidence obtained
from individual clinical trials or to provide new insights. This meta-analysis is problematic
because it incorporates doses not used in clinical practice and appears to involve analyses that
were conducted arbitrarily to yield significant results. We hope that the authors will collect real-
world data on mirikizumab in the future and present them as a meta-analysis.
• Figure 3: Based on the regulatory situation in the FDA and Japan, I understand that mirikizumab
has been approved for induction therapy at 300 mg followed by maintenance therapy at 200 mg.
Conducting a meta-analysis on the efficacy of 50 mg, 200 mg, and 600 mg induction doses has
no clinical relevance.
• Figure 4: In Figure 4A, the risk ratio crosses 1, which likely prompted the sensitivity analysis
shown in Figure 4B. However, the rationale for excluding only the Sandborn 2022 study is not
provided. Furthermore, excluding studies such as Sandborn 2020 or D’Haens 2023 would likely
result in a risk ratio crossing 1. Therefore, Figure 4 must be considered arbitrary.
• Figures 5 and 6: As with Figure 3, combining results from trials using unapproved doses in a
meta-analysis provides no meaningful clinical impact.
• Figure 7: The same concerns raised for Figure 3 also apply here. Moreover, the weight of
D’Haens 2023 is 97.3%, which is unacceptable for a meta-analysis result.
• Figure 8: The weight of D’Haens 2023 is excessively high, making the meta-analysis results
unsuitable for adoption.
• Figure 9: The same concerns as those raised for Figure 3 apply here.
• Figures 10 and 11: These figures are inappropriate for the same reasons mentioned regarding
Figure 4.
• Figure 12: Similar to Figure 7, the weight of D’Haens 2023 is excessively high, making the
results unsuitable for inclusion in the meta-analysis.
Please review this paper.
user
Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 5 Date: 28 Dec 2024
Reviewer's report:
The results presented in all Figures of the meta-analysis are inappropriate and cannot be
approved for the following reasons. The authors emphasize that this is the first meta-analysis
of mirikizumab; however, the purpose of a meta-analysis is to strengthen the evidence obtained
from individual clinical trials or to provide new insights. This meta-analysis is problematic
because it incorporates doses not used in clinical practice and appears to involve analyses that
were conducted arbitrarily to yield significant results. We hope that the authors will collect real-
world data on mirikizumab in the future and present them as a meta-analysis.
• Figure 3: Based on the regulatory situation in the FDA and Japan, I understand that mirikizumab
has been approved for induction therapy at 300 mg followed by maintenance therapy at 200 mg.
Conducting a meta-analysis on the efficacy of 50 mg, 200 mg, and 600 mg induction doses has
no clinical relevance.
• Figure 4: In Figure 4A, the risk ratio crosses 1, which likely prompted the sensitivity analysis
shown in Figure 4B. However, the rationale for excluding only the Sandborn 2022 study is not
provided. Furthermore, excluding studies such as Sandborn 2020 or D’Haens 2023 would likely
result in a risk ratio crossing 1. Therefore, Figure 4 must be considered arbitrary.
• Figures 5 and 6: As with Figure 3, combining results from trials using unapproved doses in a
meta-analysis provides no meaningful clinical impact.
• Figure 7: The same concerns raised for Figure 3 also apply here. Moreover, the weight of
D’Haens 2023 is 97.3%, which is unacceptable for a meta-analysis result.
• Figure 8: The weight of D’Haens 2023 is excessively high, making the meta-analysis results
unsuitable for adoption.
• Figure 9: The same concerns as those raised for Figure 3 apply here.
• Figures 10 and 11: These figures are inappropriate for the same reasons mentioned regarding
Figure 4.
• Figure 12: Similar to Figure 7, the weight of D’Haens 2023 is excessively high, making the
results unsuitable for inclusion in the meta-analysis.
assistant