Albumin change predicts failure in ulcerative colitis treated with adalimumab

Natsuki Ishida; Kenichi Takahashi; Yusuke Asai; Takahiro Miyazu; Satoshi Tamura; Shinya Tani; Mihoko Yamade; Moriya Iwaizumi; Yasushi Hamaya; Satoshi Osawa; Ken Sugimoto

doi:10.1371/journal.pone.0295681

Peer Review History

Original SubmissionSeptember 18, 2023
11 Oct 2023 Decision Letter - Emiko Mizoguchi, Editor PONE-D-23-29818Albumin change predicts failure in ulcerative colitis treated with adalimumabPLOS ONE Dear Professor Sugimoto, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Your manuscript was assessed by two specialized reviewers in this field, and some major issues have been raised by both reviwers as shown below. Regarding the criticisms from both reviewers, you must fully address the issues in the revised results and discussion sections. In particular, as suggested by reviewer 1, please carefully investigate if albumin changes can predict failure in ulcerative colitis patients treated with inflixmab and golimumab as well. Without providing the additional data/explanations, this manuscript will not be considered for publication in PLOS ONE. Please submit your revised manuscript by Nov 25 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. 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Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Emiko Mizoguchi, M.D., Ph.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. No Supporting Information captions Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this study, the authors demonstrated that serum albumin change was a prognostic factor for the therapeutic effect of ADA in UC. This is a very interesting result, but it is necessary to confirm whether similar findings can be obtained for other anti-TNF-alpha antibodies. Furthermore, it has been reported that the Neutrophil-to-Lymphocyte ratio (NLR) is associated with treatment failure of anti-TNF-alpha antibodies, which also needs to be investigated. I raise several concerns including this point as listed below. 1. Previous reports have shown that albumin changes are associated with treatment failure in UC patients using IFX and ADA. In Japan, it remains unclear whether albumin changes are associated only with ADA or with anti-TNF-alpha antibodies as a whole. Please investigate whether albumin changes can predict failure in UC patients treated with infliximab (IFX) and golimumab (GOM). 2. Factors such as Erythrocyte sedimentation rate and NLR should also be considered in ADA, IFX, and GOM. 3. Were there any differences between failures and non-failures in laboratory parameters at Week 6? Reviewer #2: The authors aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC, and demonstrated albumin change predicts failure in ulcerative colitis treated with adalimumab. The present study was well-organized and well-investigated, and will give us a new information, especially in the field of clinical medicine. To improve the quality of this paper, the authors should revise it according to the following suggestions; 1) This paper shows that the Week 2/week 0 Alb ratio is important as an outcome predictor of ADA treatment. However, the first problem is that the number of cases is small. 2) Week 2 Alb data is already data after ADA treatment, and it has already been shown that Week 2 Alb increases in the no-failure group. We believe that the Week 2/week 0 Alb ratio is not a predictive factor in a strict sense, but rather a factor for determining early treatment effects of ADA. 3) It has been reported that low serum Alb levels are factor in treatment failure in UC in general, regardless of treatment. It is predicted that this does not indicate the usefulness of the Week 2/week 0 Alb ratio only for ADA treatment. The Week 2/week 0 Alb ratio should also be indicated in patients who do not use ADA. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0295681.r001
Revision 1
24 Nov 2023 Author Response Emiko Mizoguchi Academic Editor PLOS ONE Dear Dr. Emiko Mizoguchi: We wish to resubmit our revised manuscript, titled “Albumin change predicts failure in ulcerative colitis treated with adalimumab.” The manuscript ID is PONE-D-23-29818. We are grateful for the opportunity to revise our manuscript, and we would like to thank the reviewers for their helpful suggestions and comments. We have addressed the concerns of the reviewers and editor, and the relevant changes have been incorporated into the revised manuscript, which are highlighted in red font. The detailed and pointwise responses to all comments have been prepared and are given below. As advised by an academic editor, we have added an analysis of infliximab and golimumab in addition to adalimumab. We believe that these revisions have strengthened our manuscript and hope that the revised manuscript is now suitable for publication in PLOS ONE. We have uploaded marked and unmarked copies of the manuscript, as requested. Sincerely, Ken Sugimoto First Department of Medicine, Hamamatsu University School of Medicine 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan Tel: +81-53-435-2261 Fax: +81-53-434-9447 E-mail: sugimken@hama-med.ac.jp Reviewer #1: In this study, the authors demonstrated that serum albumin change was a prognostic factor for the therapeutic effect of ADA in UC. This is a very interesting result, but it is necessary to confirm whether similar findings can be obtained for other anti-TNF-alpha antibodies. Furthermore, it has been reported that the Neutrophil-to-Lymphocyte ratio (NLR) is associated with treatment failure of anti-TNF-alpha antibodies, which also needs to be investigated. I raise several concerns including this point as listed below. 1. Previous reports have shown that albumin changes are associated with treatment failure in UC patients using IFX and ADA. In Japan, it remains unclear whether albumin changes are associated only with ADA or with anti-TNF-alpha antibodies as a whole. Please investigate whether albumin changes can predict failure in UC patients treated with infliximab (IFX) and golimumab (GOM). Response: Thank you for your comment. As you have pointed out, past studies have examined the prediction of treatment failure of the Alb ratio of IFX and ADA. In this revision, IFX and GOM as well as the Alb ratio analysis were added. As indicated in the limitations of the original manuscript, the number of UC patients treated with ADA in this study was small. Unfortunately, the sample size was even smaller with 14 and 20 patients receiving IFX and GOM, respectively. As it was considered difficult to obtain statistically significant results for GOM and IFX separately, we added the same analysis for all anti-TNF-α antibody preparations: ADA, GOM, and IFX. The results of this analysis have been added to the newly added “Examination of the week 2/week 0 Alb ratio in patients with anti-tumor necrosis factor-α antibodies treated” section (Page 13, Lines 212-225). Of the 68 patients who received ADA, GLM, and IFX, 20 had treatment failure. Patient demographics are shown in the newly added Supplemental Table 4. The Alb ratio of the failure group was significantly lower than that of the non-failure group (P < 0.001). The cutoff value for the week 2/week 0 Alb ratio in the ROC analysis for predicting treatment failure was 0.98. Kaplan–Meier analysis was performed between the Alb ratio ≥0.98 and <0.98 groups, and the log-rank test showed a significant difference (P < 0.001). As mentioned above, the analysis that included GLM and IFX also demonstrated the usefulness of the Alb ratio for predicting treatment failure. Furthermore, it is desirable to investigate the usefulness of the Alb ratio in the analysis of IFX and GLM, and it is hoped that more cases will be accumulated (Page 17, Line 315-319). 2. Factors such as Erythrocyte sedimentation rate and NLR should also be considered in ADA, IFX, and GOM. Response: Thank you for your comment. We greatly appreciate the reviewers’ advice. As mentioned above, due to the small sample size, it was not possible to conduct an analysis on IFX and GOM, but we added an analysis on the leukocyte subtype. Leukocyte subtype measurements were not performed in two patients before induction, and analysis was conducted only in 32 patients (19 non-failure versus 13 failure). A significant difference test was performed on the leukocyte subtype (neutrophile, lymphocyte, and monocyte), the absolute count, and leukocyte subtype ratio (neutrophile to lymphocyte ratio [NLR], neutrophile to monocyte ratio [NMR], and lymphocyte to monocyte ratio [LMR]). There were no significant differences between the two groups in these variables. Other studies showed significant differences in NLR, but this may be due to differences in sample size and endpoints. We have presented these results in Supplemental Table 1 and also included them in the Results and Discussion section (Page 9, Line 157–159) (Page 16, Line 282–286). 3. Were there any differences between failures and non-failures in laboratory parameters at Week 6? Response: Thank you for your comment. we compared the biological data of the failure and non-failure groups at week 6. Further exclusion of three patients with treatment failure resulted in a comparison of 10 and 21 patients with and without treatment failure respectively. There were no significant differences between the two groups in Alb, CRP, WBC, Hb, and Plt level at week 6. It is possible that cases of early treatment failure were eliminated, leaving only cases with treatment failure with relatively good data. However, the week 2/week 0 Alb ratio, which is an earlier evaluation, was more predictive of the subsequent clinical course than the week 6 data. This result will be added to the Results section (Page 9, Lines 159-161). Reviewer #2: The authors aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC, and demonstrated albumin change predicts failure in ulcerative colitis treated with adalimumab. The present study was well-organized and well-investigated, and will give us a new information, especially in the field of clinical medicine. To improve the quality of this paper, the authors should revise it according to the following suggestions; 1) This paper shows that the Week 2/week 0 Alb ratio is important as an outcome predictor of ADA treatment. However, the first problem is that the number of cases is small. Response: Thank you for your comment. A major problem with this study is that it had a small sample size and was barely enough to perform statistical analysis. Additionally, the fact that the albumin ratio was significantly different between the two groups despite the small sample size shows the usefulness of the albumin ratio. This comment was added in the Discussion section (Page 19, Lines 314–315). 2) Week 2 Alb data is already data after ADA treatment, and it has already been shown that Week 2 Alb increases in the no-failure group. We believe that the Week 2/week 0 Alb ratio is not a predictive factor in a strict sense, but rather a factor for determining early treatment effects of ADA. Response: Thank you for your comment. The Alb ratio may indicate early treatment effects of ADA. However, treatment effects do not always indicate subsequent prognosis, and not all treatment effects at week 2 indicate subsequent outcomes. The results of this analysis show that the week 2/week 0 Alb ratio can be a predictive factor for treatment failure. However, the reviewer’s recognition of early treatment effects of ADA is important and has been added to the discussion section (Page 19, Lines 299–300). 3) It has been reported that low serum Alb levels are factor in treatment failure in UC in general, regardless of treatment. It is predicted that this does not indicate the usefulness of the Week 2/week 0 Alb ratio only for ADA treatment. The Week 2/week 0 Alb ratio should also be indicated in patients who do not use ADA. Response: Thank you for your comment. The usefulness of the week 2/week 0 Alb ratio has already been demonstrated in studies on ADA and IFX. In addition to ADA, the editor and reviewer 1 also recommended analysis of IFX and GLM, but these drugs did not have a sufficient sample size to statistically analyze the data. We will conduct another analysis if more cases are accumulated. Thus, this study focused only on ADA. Accordingly, we have added a comment to the text regarding the fact that IFX and GLM analysis could not be performed (Page 16, Lines 279–282) Attachments Attachment Submitted filename: R1 Response to reviewer.docx https://doi.org/10.1371/journal.pone.0295681.r002
28 Nov 2023 Decision Letter - Emiko Mizoguchi, Editor Albumin change predicts failure in ulcerative colitis treated with adalimumab PONE-D-23-29818R1 Dear Dr. Ken Sugimoto: We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Emiko Mizoguchi, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: (No Response) Reviewer #2: The authors responded to our suggestions and carefully revised, especially in the Discussion. We have no claim in the revised paper. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0295681.r003
Formally Accepted
20 Dec 2023 Acceptance Letter - Emiko Mizoguchi, Editor PONE-D-23-29818R1 PLOS ONE Dear Dr. Sugimoto, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Emiko Mizoguchi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0295681.r004

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