Dupilumab in Children and Adolescents with Severe Atopic Dermatitis and Severe Asthma: A Case Series

Round 1

Reviewer 1 Report

Attached file

Comments for author File: Comments.pdf

Minor editing of English language required

Author Response

Here is a point-by-point response to the reviewer's comments and concerns.

Introduction

- The authors jump from discussing the burden of asthma and atopic dermatitis to the pathologic mechanisms of asthma without making a smooth transition. It would be beneficial to reorganize the information and create a clear and logical progression of ideas.

Thank you for this suggestion. We revised the paper as suggested reorganizing information and ideas.

 

- Spell out acronyms and initialisms in full the first time they are used in the text and then use the abbreviation throughout the rest of the text. Examples, atopic dermatitis (AD) and quality of life (QoL).

All acronyms werse revised as requested and the text was more carefully reviewed.

 

- The authors should integrate the information about asthma and AD instead of presenting them separately since they often occur together and have common underlying mechanisms.

Thank you for this suggestion, we followed it in the introduction.

 

- Please correct the format of writing interleukin. Remove special characters. The correct format is "IL-8, IL-17, IL-22."

Thank you for this suggestion, we corrected this typo.

 

Methods

- Please indicate how the data were collected, whether through patient records, surveys, or other methods.

Thank you for this suggestion, we better explained data collection in the text.

 

- Please briefly explain the U.K. Working Party's diagnostic criteria and GINA guidelines.

Thank you for this suggestion, we explained them in the text.

 

- Please specify the treatment duration for each participant.

Thank you for this suggestion, we specified it in the text for each patient.

 

Case 1

- I understood from the text that the authors relied only on patients' subjective reports of symptoms and improvements. If this is true, why did the authors not use an objective clinical scoring system?

Thank you for this comment. We used standardized questionnaires (SCORAD and EASI) for AD based on both subjective reports and objective measurements (i.e. physician’s evaluation of body surface involvement and the severity of atopic dermatitis); we also used valid and reliable subjective scores such as P-NRS, S-NRS and CLDQI. Additionally, we used for asthma both a standardized questionnaire evaluating asthma control (ACT), based on patients’ subjective reports, and spirometry which gave us objective measurements of the lung function.

 

- The duration of previous treatments such as cyclosporine A and inhaled fluticasone is not mentioned in the text.

Thank you for this suggestion, we specified it in the text.

 

Case 3

- There is no mention of the long-term follow-up and sustained benefits. This is also valid for the cases.

Thank you for this comment. We mentioned them in the text.

 

Case 5

- No mention is made of how SARS-CoV-2 infection may have affected the patient's treatment or overall condition.

Thank you for this comment. We didn’t mention it because SARS-CoV-2 infection in that patient was asymptomatic and it could have not affected the patient’s treatment or overall condition (Wollenberg, A., Flohr, C., Simon, D., Cork, M.J., Thyssen, J.P., Bieber, T., de Bruin-Weller, M.S., Weidinger, S., Deleuran, M., Taieb, A., et al. (2020), European Task Force on Atopic Dermatitis statement on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and atopic dermatitis. J Eur Acad Dermatol Venereol, 34: e241-e242. https://doi.org/10.1111/jdv.16411). Additionally, we thought that to better explain this aspect was beyond the aim of our manuscript and could be confusing for the reader.

 

Case 6

- The dosage regimen of 600 mg at time 0 and 300 mg every 15 days is mentioned without clearly explaining how this dosage was determined.

- Thank you for this clarification. We better explained in the text how the dosage in that patient was determined.

 

Results and Conclusions

- The study only reports the results at 12 weeks of treatment. It would be valuable to have longer-term follow-up data to assess the sustainability of the observed improvements and to identify any potential relapses or side effects over time. Although the authors mention mild side effects in some patients, it does not provide a comprehensive assessment of the safety profile of dupilumab. A more detailed analysis of potential side effects and long-term safety is needed to fully evaluate the risks and benefits of treatment.

 

Thank you the referee for that interesting comment. We didn’t have longer-term follow-up data for all patients. However, we highlight that this case series describing childhood asthma and AD in treatment with dupilumab may show clinical data (outside clinical trials) aiming to may add further clinical evidence form real-life and also suggest the potential role of dupilumab to interrupt the atopic pathways from AD to asthma in the first years of life in selected cases.

 

- The authors need to acknowledge and clearly state the limitations of their study.

Thank you for this suggestion. We described in the text the limitations of our study.

Reviewer 2 Report

The manuscript described seven cases of moderate to severe atopic dermatitis, some with severe asthma, in children treated with a monoclonal antibody, Dupilumab.

Overall, extensive English editing is required for this manuscript since, on many occasions, the sentences are hard to understand or need speculation.

 

Moreover, with seven cases presented and little to no quantitative analysis, I find it hard to reach any conclusion or indications with this manuscript. In addition, as mentioned in this manuscript (especially ref. 23.25), there were multiple clinical trials and meta-analyses of those clinical trials which provided more apprehensive analysis in the same matter, and the use of dupilumab in children has been approved. Hence, I am unsure what additional benefits readers would obtain from this current manuscript. 

 

1.       Line 31, this sentence is confusing. Please edit.

2.       Line 39, please edit the citation format.

3.       Line 51-52, please edit the citation format – move the citation to the end of the sentence.

4.       Line 60, “T2 – low”, the abbreviation occurred without full spelling. And on line 63, the abbreviation appears different, as in “T – 2 - high”. Please unify the names.

5.       Line 64, this sentence needs to be edited.

6.       Line 78, please provide a reference.

7.       Line 119, this sentence needs to be edited.

8.       Line 97 & Line 192, please consider adding a detailed explanation of the indications of the scores.

9.       Line 195-196, please consider adding more detail than a “reduction”.

 

10.   For each case, the overall content was very descriptive, without much quantitative information and reference to the information in the table. It would be better if more information were discussed in each case.  

Extensive editing of the English language required

Author Response

1. Line 31, this sentence is confusing. Please edit.
2. Line 39, please edit the citation format.
3. Line 51-52, please edit the citation format – move the citation to the end of the sentence.
4. Line 60, “T2 – low”, the abbreviation occurred without full spelling. And on line 63, the abbreviation appears different, as in “T – 2 - high”. Please unify the names.
5. Line 64, this sentence needs to be edited.
6. Line 78, please provide a reference.

Thank you for all these suggestions. We completely edited the sentences in the introduction in order to create a clear and logical progression of ideas with more simple and linear concepts.

 

7. Line 119, this sentence needs to be edited.

Thank you for this suggestion. We edited the sentence as request.

 

8. Line 97 & Line 192, please consider adding a detailed explanation of the indications of the scores.

Thank you for this suggestion. We better described all the cited scores.

 

9. Line 195-196, please consider adding more detail than a “reduction”.

Thank you for this suggestion. We better described it in our table. 

 

10. For each case, the overall content was very descriptive, without much quantitative information and reference to the information in the table. It would be better if more information were discussed in each case.  

Thank you, the referee, for that interesting comment that shows study limitations. We highlighted study limitations in the text and tried to provide more information. We described main patients’ characteristics and scores/spirometric parameters in our table. Our data aimed at supporting not only the evidence in the literature but also hypothetically suggesting the potential role of dupilumab to interrupt the atopic pathways from AD to asthma in the first years of life.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

With seven cases presented and little to no quantitative analysis, I find it hard to reach any conclusion or indications with this manuscript. In addition, as mentioned in this manuscript (especially ref. 23.25), there were multiple clinical trials and meta-analyses of those clinical trials which provided more apprehensive analysis in the same matter, and the use of dupilumab in children has been approved. Hence, I am unsure what additional benefits readers would obtain from this current manuscript. 

Moderate editing of English language required

Author Response

With seven cases presented and little to no quantitative analysis, I find it hard to reach any conclusion or indications with this manuscript. In addition, as mentioned in this manuscript (especially ref. 23.25), there were multiple clinical trials and meta-analyses of those clinical trials which provided more apprehensive analysis in the same matter, and the use of dupilumab in children has been approved. Hence, I am unsure what additional benefits readers would obtain from this current manuscript. 

-Thank you for reviewing our paper. We understand the opinion of the reviewer yet, this is a case series taken from our clinical practice that adds real life clinical data. Recently, Votto et al (DOI 10.1111/pai.13623) also described a rapid response to dupilumab treatment in children with moderate-to-severe atopic dermatitis in a case series with a similar aim. Additionally, a case series includes a description of the characteristics and outcomes among a group of individuals with either a disease or an exposure (which can be an intervention) over a period of time and without a control group. Data are collected retrospectively and there is no randomization with no quantitative analysis (DOI 10.36416/1806-3756/e20200389).

We have expanded on this concept in the limitation section of our manuscript.

 

Comments on the Quality of English Language

Moderate editing of English language required

 

-We thank the referee for the comment. The manuscript was edited and reviewed for English improvement.