Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease

Rebecca H Haberman; Ramin Herati; David Simon; Marie Samanovic; Rebecca B Blank; Michael Tuen; Sergei B Koralov; Raja Atreya; Koray Tascilar; Joseph R Allen; Rochelle Castillo; Amber R Cornelius; Paula Rackoff; Gary Solomon; Samrachana Adhikari; Natalie Azar; Pamela Rosenthal; Peter Izmirly; Jonathan Samuels; Brian Golden; Soumya M Reddy; Markus F Neurath; Steven B Abramson; Georg Schett; Mark J Mulligan; Jose U Scher

doi:10.1136/annrheumdis-2021-220597

Responses

PDF

PDF +
Supplementary
Material

XML

Epidemiology

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease

Compose a Response to This Article

Compose Response

Title *

Author Information

Contributors
First Name and Middle Initial * First or given name, e.g. 'Peter'. Last Name * Your last, or family, name, e.g. 'MacMoody'. Email Address * Your email address, e.g. higgs-boson@gmail.com Occupation * Your role and/or occupation, e.g. 'Orthopedic Surgeon'. Affiliation * Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.

Statement of Competing Interests

Competing interests? *

Yes

Please describe the competing interests

PLEASE NOTE:

A rapid response is a moderated but not peer reviewed online response to a published article in a BMJ journal; it will not receive a DOI and will not be indexed unless it is also republished as a Letter, Correspondence or as other content. Find out more about rapid responses.
We intend to post all responses which are approved by the Editor, within 14 days (BMJ Journals) or 24 hours (The BMJ), however timeframes cannot be guaranteed. Responses must comply with our requirements and should contribute substantially to the topic, but it is at our absolute discretion whether we publish a response, and we reserve the right to edit or remove responses before and after publication and also republish some or all in other BMJ publications, including third party local editions in other countries and languages
Our requirements are stated in our rapid response terms and conditions and must be read. These include ensuring that: i) you do not include any illustrative content including tables and graphs, ii) you do not include any information that includes specifics about any patients,iii) you do not include any original data, unless it has already been published in a peer reviewed journal and you have included a reference, iv) your response is lawful, not defamatory, original and accurate, v) you declare any competing interests, vi) you understand that your name and other personal details set out in our rapid response terms and conditions will be published with any responses we publish and vii) you understand that once a response is published, we may continue to publish your response and/or edit or remove it in the future.
By submitting this rapid response you are agreeing to our terms and conditions for rapid responses and understand that your personal data will be processed in accordance with those terms and our privacy notice.

I agree to and have read the terms and conditions for rapid responses and BMJ Privacy Notice *

CAPTCHA

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

Other responses

Jump to comment:

Comment on Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease by Haberman et al
Chih-Wei Chen, James Cheng-Chung Wei
Published on: 13 September 2021

Published on: 13 September 2021
Comment on Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease by Haberman et al
- Chih-Wei Chen, Member/PhD student National Council for Sustainable Development, Executive Yuan, Taiwan Govt./Institute of Medicine, Chung Shan Medical University
- Other Contributors:
  James Cheng-Chung Wei, Professor
Comment on Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease by Haberman et al

Chih-Wei Chen, James Cheng-Chung Wei

Chih-Wei Chen, FRGS
National Council for Sustainable Development, Executive Yuan, Taiwan Govt.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
E-mail: chihwei.chen@udm.global

James Cheng-Chung Wei, MD, PhD.
Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan. (TEL)＋886 4 24739595 #34718. (FAX) +886 4 24637389, E-mail: jccwei@gmail.com

Correspondence: James Cheng-Chung Wei

We read with great interest the research by Haberman et al. regarding the BNT162b2 mRNA vaccine in patients with immune-mediated inflammatory diseases (IMID) and effect of methotrexate. We appreciate authors important contribution to understanding the efficacy of vaccine in IMID and developing vaccination strategies (1). However, there are still worthwhile issues that need to be concerned.

The authors conducted investigation in healthy people and pa...
Show More

Comment on Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease by Haberman et al

Chih-Wei Chen, James Cheng-Chung Wei

Chih-Wei Chen, FRGS
National Council for Sustainable Development, Executive Yuan, Taiwan Govt.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
E-mail: chihwei.chen@udm.global

James Cheng-Chung Wei, MD, PhD.
Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan. (TEL)＋886 4 24739595 #34718. (FAX) +886 4 24637389, E-mail: jccwei@gmail.com

Correspondence: James Cheng-Chung Wei

We read with great interest the research by Haberman et al. regarding the BNT162b2 mRNA vaccine in patients with immune-mediated inflammatory diseases (IMID) and effect of methotrexate. We appreciate authors important contribution to understanding the efficacy of vaccine in IMID and developing vaccination strategies (1). However, there are still worthwhile issues that need to be concerned.

The authors conducted investigation in healthy people and patients with IMID (either treated by methotrexate or not), and concluded that the methotrexate treatment adversely affected the efficacy of BNT 162b2 vaccine in patients with IMID. However, the conducted investigations could not fully support the conclusion as limited sample size (26 IMID patients, 25 IMID patients with methotrexate treatment) were employed in the investigation. Within such limited sample size, the IMID patients were aged between 29-79 with an average number of 49.1, whereas the IMID patients treated by methotrexate were aged between 22-77 with an average number of 63.2. The patients’ age was ranged between 20s and 70s, but other age groups (e.g. under 20 or over 80) were not considered. Meanwhile, the average age of patients treated by methotrexate was older than patients without methotrexate treatment. Alternatively, approximately 65% investigated people (either healthy people or patients) were female, whereas male accounts for around 35%. The above-mentioned conditions could all weaken the conclusion that it is the methotrexate treatment that adversely affected the efficacy of BNT vaccine in IMID patients. Overall, the sample size of the investigated people was limited and the groups of people with different characteristics were imbalance, which were therefore not enough to cover all the people. Hence, it is necessary to enlarge the sample size, i.e. investigate more people with more comprehensive characteristics, to achieve valid conclusions.

In general, sample size of a clinical research could be calculated by:

N=2 (〖(a+b)〗^2 σ^2)/〖(μ_1-μ_2)〗^2

where N is the sample size of each group, a and b represent conventional multiplier for type I and type II errors, σ^2 represents population variance (SD), μ_1 and μ_2 represent population mean in treatment group and control group, μ_1-μ_2 represents minimal clinically relevant difference. (2)

It is suggested that clinical-related parameters should be assumed based on previous experiment results (2), therefore we employ the results of (1) to obtain the parameters. we assume the type I error of 0.05 (a=1.96), type II error of 0.2 (b=0.842). Meanwhile, we choose σ, μ_1, and μ_2 from the results in (1) to represent the antibody response titer, and therefore are 179000, 145000, 142000, respectively. Hence, based on the formula, 709 IMID patients treated by methotrexate are necessary to conduct the investigation. It should be noted that the sample size calculation is highly sensitive to determined parameters, and therefore cautious calculations or statistical advice could be helpful when designing the sample size (2).

Scientists predicted that COVID-19 caused by an mRNA virus is very likely or likely to become an endemic virus (3), due to high possibility of mutation and much higher contagious. The development of varieties of vaccination strategies to cover all people is important to contain the spread of the virus and save lives. To boost the immune response of BNT vaccine in IMID patients treated by methotrexate, the author provided three strategies: (a) additional doses of vaccine, (b) dosemodification of methotrexate, and (c) temporary discontinuation of methotrexate. BNT vaccine investigated in the paper is an mRNA vaccine, and Moderna vaccine (4) is another mRNA-based vaccine that is potential to be an alternative to BNT vaccine. Hence, it is necessary to investigate the efficacy of Moderna vaccine in IMID patients treated by methotrexate and whether the strategies proposed by authors could be applied in Moderna vaccine. As a matter of fact, different types of vaccines based on various mechanisms could provide different protection efficacy in people. Apart from mRNA-based vaccines, vaccines based on different mechanisms are also potential options, such as viral vector-based vaccines, i.e. AstraZeneca and Janssen vaccines (also called Johnson & Johnson vaccine), as well as the subunit vaccine, i.e. Novavax vaccine (5-7). It is also necessary to investigate the efficacy of vaccines with different mechanisms and explore better vaccination strategies to achieve higher immune response for all people.

Above all, the research conducted by Haberman et al. contributes to understanding the efficacy of vaccine in IMID patients with methotrexate treatment. Further investigations are necessary to enlarge the sample size of investigated people with various characteristics, as well as considering different types of vaccines based on various mechanisms. Under such circumstance, the development of various vaccination strategies for all people will provide valuable reference to guide medical professionals in the clinical work. Meanwhile, giving vaccines to more people will contribute to containing the spread of COVID-19 pandemic and save lives.

REFERENCES

1. Haberman RH, Herati RS, Simon D, et al. Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease. Annals of the Rheumatic Diseases. 2021. doi: 10.1136/annrheumdis-2021-220597.
2. Noordzij M, Tripepi G, Dekker FW, et al. Sample size calculations: basic principles and common pitfalls. Nephrology Dialysis Transplantation. 2010. 25(5):1388-93.
3. Phillips N, The coronavirus is here to stay — here’s what that means. 2021. doi: https://doi.org/10.1038/d41586-021-00396-2.
4. Moderna. Moderna’s work on our COVID-19 vaccine. 2021. Retrieved from: https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19 (Accessed: 18 June 2021).
5. Pfizer. Pfizer and BioNTech announced vaccine candidate against COVID-19 achieved success in first interim analysis from phase 3 study. 2021. Retrieved from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-an... (Accessed: 18 June 2021).
6. Centres for Disease Control and Prevention. Johnson & Johnson’s Janssen COVID-19 Vaccine Overview and Safety. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/ja... (Accessed: 18 June 2021).
7. Novavax. All updates on our COVID-19 vaccine efforts. Retrieved from: https://www.novavax.com/covid-19-coronavirus-vaccine-candidate-updates (Accessed: 18 June 2021).
Show Less

Conflict of Interest:
None declared.
- Back to top

Main menu

Plain text

PLEASE NOTE:

Vertical Tabs

Other responses

Jump to comment:

Log in using your username and password

Main menu

Log in using your username and password

You are here

Plain text

PLEASE NOTE:

Vertical Tabs

Other responses

Jump to comment:

Read the full text or download the PDF:

Log in using your username and password