Should the Cat Stay Home? A Guide to Managing Cat Allergies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for giving me the opportunity to review this manuscript. This is a well-organized and comprehensive account of possible measures and actions that can be undertaken in order to reduce the cat allergen exposure, as well as possible clinical implications of such actions.

I have nothing to raise with regard to the structure and majority of the content of the manuscript.

My only concern is related to sections 1.11 and 1.12, i.e. the description of therapeutic options in allergy to cat. For me, these sections seem not to be relevant and congruous with the remaining part and main topic of the review. I think the Authors may consider deleting them (at their dicretion), since these paragraphs only very briefly mention treatment modalities (pharmacotherapy, anti-IgE) which are common to other allergies and not limited to cat allergy. Besides, anti-IgE implementation in allergic rhinitis has not reached beyond clinical trials phase and. Moreover, it is not designed to treat cat allergy specifically, therefore, these sections can be removed without influencing the quality of the manuscript. On the contrary, the immunotherapy section 1.13 is absolutely relevant and can be kept in the text.

Otherwise, no issued to be raised on my part.

Author Response

Manuscript (Submission ID allergies-3410875)

Response to Reviewers

Dear Editorial Board,

Thank you for giving us the opportunity to submit a revised manuscript to Allergies

We appreciate the time and effort that you and the reviewers dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions made by the reviewers. Those changes are highlighted within the manuscript. Please see below, in blue, for a point-by-point response to the reviewers’ comments and concerns.

Reviewers' Comments to the Authors:

“Thank you for giving me the opportunity to review this manuscript. This is a well-organized and comprehensive account of possible measures and actions that can be undertaken in order to reduce the cat allergen exposure, as well as possible clinical implications of such actions.

I have nothing to raise with regard to the structure and majority of the content of the manuscript.

My only concern is related to sections 1.11 and 1.12, i.e. the description of therapeutic options in allergy to cat. For me, these sections seem not to be relevant and congruous with the remaining part and main topic of the review. I think the Authors may consider deleting them (at their dicretion), since these paragraphs only very briefly mention treatment modalities (pharmacotherapy, anti-IgE) which are common to other allergies and not limited to cat allergy. Besides, anti-IgE implementation in allergic rhinitis has not reached beyond clinical trials phase and. Moreover, it is not designed to treat cat allergy specifically, therefore, these sections can be removed without influencing the quality of the manuscript. On the contrary, the immunotherapy section 1.13 is absolutely relevant and can be kept in the text.

Otherwise, no issued to be raised on my part"

AUTHOR RESPONSE:

We sincerely thank you for your thorough review of our manuscript and for providing valuable feedback on sections 1.11, 1.12, and 1.13. Below, we address your comments regarding these sections:

We acknowledge your concern that sections 1.11 and 1.12, which briefly describe pharmacotherapy and anti-IgE treatments, may not be fully congruent with the main topic of the review. As you correctly pointed out these treatment modalities are general approaches to allergic conditions and are not specific to cat allergy. Anti-IgE therapy, in particular, has not progressed beyond the clinical trial phase for allergic rhinitis and is not specifically designed to treat cat allergy. Considering these points, we agree that the inclusion of these sections does not significantly enhance the quality or focus of the manuscript. Therefore, we have decided to remove sections 1.11 and 1.12 to streamline the content and ensure alignment with the main topic. We appreciate your acknowledgment of the relevance of section 1.13, which discusses immunotherapy. As immunotherapy represents a specific and promising therapeutic option for cat allergy, we have retained this section in the manuscript. We believe these changes enhance the clarity and focus of the manuscript and align it more closely with the review's main objective. Thank you again for your valuable insights, which have been instrumental in improving the manuscript.

 

Reviewer 2 Report

Comments and Suggestions for Authors

This is a review on the interventions available for cat allergy. The review is comprehensive and well structured. Below are suggestions to improve:

 

1.       Please make each subsection more balanced as this review article feels biased towards AIT and biologics. The environmental control measures are written in more discouraging tones highlighting its limitations and ignoring its strength. On the other hand,  limitations AIT and biologics intervention not mentioned, eg. cost, patient selection and contraindications (AIT is contraindicated for severe uncontrolled bronchial asthma). Suggest adding some data in these subsections to support the strengths and limitations.  

2.       Suggest to expand on hypoallergenic cats. Any scientific evidence of this?

3.       Please add some data on the safety of Feld1 vaccine so far

4.       Please mention the duration of treatment for Tezepelumab. How long should it be concurrently administered with AIT?

5.       In the diagnostic algorithm, since most interventions focus on Feld1, do you recommend testing for Feld1 instead of whole allergen?

6.       Table 1 is not mentioned in text.

Author Response

Manuscript (Submission ID allergies-3410875)

Response to Reviewers

Dear Editorial Board,

Thank you for giving us the opportunity to submit a revised manuscript to Allergies

We appreciate the time and effort that you and the reviewers dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions made by the reviewers. Those changes are highlighted within the manuscript. Please see below, in blue, for a point-by-point response to the reviewers’ comments and concerns.

Reviewers' Comments to the Authors:

Reviewer 2

“This is a review on the interventions available for cat allergy. The review is comprehensive and well structured. Below are suggestions to improve:”

1. Please make each subsection more balanced as this review article feels biased towards AIT and biologics. The environmental control measures are written in more discouraging tones highlighting its limitations and ignoring its strength. On the other hand, limitations AIT and biologics intervention not mentioned, eg. cost, patient selection and contraindications (AIT is contraindicated for severe uncontrolled bronchial asthma). Suggest adding some data in these subsections to support the strengths and limitations.  
2. Suggest to expand on hypoallergenic cats. Any scientific evidence of this?
3. Please add some data on the safety of Feld1 vaccine so far
4. Please mention the duration of treatment for Tezepelumab. How long should it be concurrently administered with AIT?
5. In the diagnostic algorithm, since most interventions focus on Feld1, do you recommend testing for Feld1 instead of whole allergen?
6. Table 1 is not mentioned in text."

AUTHOR RESPONSE:

Thank you for your thorough review and valuable feedback. We appreciate the opportunity to improve our manuscript by addressing your concerns. Below, we provide detailed responses to your comments and outline the corresponding changes made to the manuscript.

We believe these revisions address your concerns and enhance the quality and balance of the manuscript. Thank you again for your constructive comments, which have significantly improved the article. We look forward to your feedback on the revised version.

1. “Please make each subsection more balanced as this review article feels biased towards AIT and biologics. The environmental control measures are written in more discouraging tones highlighting its limitations and ignoring its strength. On the other hand, limitations AIT and biologics intervention not mentioned, eg. cost, patient selection and contraindications (AIT is contraindicated for severe uncontrolled bronchial asthma). Suggest adding some data in these subsections to support the strengths and limitations. “

We have attempted to adjust the tone and content in all relevant sections for consistency and neutrality. We agree with your observation and have updated the manuscript to include a more comprehensive discussion of the limitations and contraindication of AIT.

Lines 247-254: “Allergen immunotherapy (AIT) does have some important limitations and contraindications. It requires long-term commitment, and benefits take months to years to manifest. Compliance can be challenging due to frequent dosing and potential adverse reactions, including anaphylaxis. Furthermore, there are several contraindication to consider including severe-uncontrolled asthma and the use of beta-blockers. Other contraindications are severe cardiovascular disease, immune deficiencies, pregnancy (for initiation), and acute infections. Careful patient selection and risk assessment are essential for safe and effective AIT use.”

Anti-IgE therapy, in particular, has not progressed beyond the clinical trial phase for allergic rhinitis and is not specifically designed to treat cat allergy so we decided to omit this section from the text.

2. Suggest to expand on hypoallergenic cats. Any scientific evidence of this?

Although there are no definitive studies that conclusively validate the existence of truly hypoallergenic cats we expanded by providing the following statement:

Line 55: “Certain breeds are often considered "hypoallergenic" due to anecdotal claims that they produce lower levels of Fel d 1. However, analysis has revealed significant variability even among cats of the same breed, and no breed is entirely free of allergens.”

3. Please add some data on the safety of Feld1 vaccine so far

We have added data on the safety of the Fel d 1 vaccine:

Line 188: Early clinical trials have demonstrated that the vaccine is well-tolerated. Comprehensive bloodwork, as well as kidney and liver function tests, indicated no notable side effects, and vaccinated cats maintained normal activity levels. Short-term studies suggest a favorable safety profile, with mild injection-site reactions, such as redness or swelling, being the only reported side effects in isolated cases. However, limited data are available on its use in pregnant or lactating cats, and long-term effects are still being evaluated. Importantly, trials have shown that the vaccine can reduce Fel d 1 levels by up to 50-60%, significantly decreasing allergen levels in the home environment without negatively impacting the cat’s health. Although the vaccine’s safety and efficacy appear promising, ongoing research and post-market monitoring are essential to confirm its long-term safety.

4. Please mention the duration of treatment for Tezepelumab. How long should it be concurrently administered with AIT?

We have added the duration of treatment for Tezepelumab:

Line 263: “Participants were randomly assigned to one of four groups: tezepelumab plus AIT, te-zepelumab plus placebo injections, placebo plus AIT, or double placebo for 52 weeks, followed by 52 weeks of observation.”

5. In the diagnostic algorithm, since most interventions focus on Feld1, do you recommend testing for Feld1 instead of whole allergen?

Testing for Feld1 (the major cat allergen) instead of the whole allergen is often a more focused, particularly when most interventions are designed to mitigate exposure to this specific allergen. Feld1 is the primary protein responsible for cat-related allergic reactions, making it a highly specific marker for identifying sensitization. By testing directly for Feld1, diagnostics align closely with actionable outcomes, such as implementing targeted interventions like air purifiers, cleaning regimens, or hypoallergenic cats, which are specifically aimed at reducing Feld1 exposure. This targeted approach also enhances efficiency by avoiding unnecessary complexity associated with whole-allergen testing, which includes minor or less relevant allergens. Additionally, sensitization to Feld1 strongly correlates with clinical symptoms, making it a reliable predictor for allergy management.

However, there are scenarios where whole-allergen testing may be beneficial. In cases where cross-reactivity with other allergens (e.g., lipocalins from other animals) is suspected, whole-allergen testing can help distinguish specific sensitivities. In research or epidemiological studies, whole-allergen data may also offer valuable insights into sensitization trends. Overall, for clinical management, if the primary focus is on interventions targeting Feld1, testing for this allergen specifically is recommended.

6. Table 1 is not mentioned in text

Thank you for this observation. We have referenced table 1 in the text, see line 284.