Sir, we read with interest the recent communication by Priori et al. (2021) reporting that patients with rheumatic musculoskeletal diseases (RMDs) in Italy are less willing to receive the COVID-19 vaccination than healthy controls and that they are more likely to perceive themselves at higher risk of becoming infected with SARS-CoV-2 and developing severe COVID-19 [1]. These data are somehow at odds with our observations from patients with RMDs from other seven European countries who took part in the REUMAVID study [2].
REUMAVID is an international cross-sectional study using an online survey of unselected patients with 15 RMDs from seven European countries (United Kingdom, Spain, Italy, France, Portugal, Greece, and Cyprus). A total of 2,002 patients participated in the second phase between February and April 2021. At that time, the European Medicines Agency (EMA) had approved four COVID-19 vaccines: BioNTech Pfizer, Moderna, Oxford AstraZeneca, and Janssen [3]. Significant differences in the roll out speed and vaccine availability between countries contributed to global anxiety created by the rapid development of the vaccines. Like our Italian colleagues, we were keen to explore patients’ willingness to get the vaccination and factors associated with possible unwillingness to do so.
Contrary to the report by Priori et al. (2021), our results show that the majority of survey respondents were either willing to be (82.8%, n= 1,657) or had already been vaccinat...
Sir, we read with interest the recent communication by Priori et al. (2021) reporting that patients with rheumatic musculoskeletal diseases (RMDs) in Italy are less willing to receive the COVID-19 vaccination than healthy controls and that they are more likely to perceive themselves at higher risk of becoming infected with SARS-CoV-2 and developing severe COVID-19 [1]. These data are somehow at odds with our observations from patients with RMDs from other seven European countries who took part in the REUMAVID study [2].
REUMAVID is an international cross-sectional study using an online survey of unselected patients with 15 RMDs from seven European countries (United Kingdom, Spain, Italy, France, Portugal, Greece, and Cyprus). A total of 2,002 patients participated in the second phase between February and April 2021. At that time, the European Medicines Agency (EMA) had approved four COVID-19 vaccines: BioNTech Pfizer, Moderna, Oxford AstraZeneca, and Janssen [3]. Significant differences in the roll out speed and vaccine availability between countries contributed to global anxiety created by the rapid development of the vaccines. Like our Italian colleagues, we were keen to explore patients’ willingness to get the vaccination and factors associated with possible unwillingness to do so.
Contrary to the report by Priori et al. (2021), our results show that the majority of survey respondents were either willing to be (82.8%, n= 1,657) or had already been vaccinated against SARS-CoV-2 (8.4%, n= 168), compared to only 8.8% (n= 177) who were unwilling. This is consistent with previous evidence showing that the risk of contracting the SARS-CoV-2 virus or developing the COVID-19 infection is similar in patients with RMDs in comparison to the general population [4]. Reasons for unwillingness to undergo vaccination included the fear of adverse effects (60.5%, n= 92), waiting for a new vaccine with reported greater efficacy (56.6%, n= 86), self-perception of having a compromised immune system (30.3%, n= 46), not being afraid of the virus (7.9%, n= 12) or being an anti-vaxxer (2.6%, n=4). Interestingly, those in younger age categories (OR= 0.98) and females (OR= 1.66) were associated with unwillingness to be vaccinated as demonstrated by Priori et al. (2021). In addition, having greater fears about possible adverse effects of the vaccine (OR= 1.77) or less fear that there will be enough vaccines (OR= 0.85), having less hope about the availability of an effective vaccine (OR= 0.51) or of achieving protection against COVID-19 (OR= 0.43) were also associated with unwillingness to be vaccinated. Importantly, patients expressed a fear that clinical trials of these vaccines may not have included patients with RMDs on immunosuppressive therapies [5]. Surprisingly, patients who had never taken biologics were less willing to be vaccinated (OR= 1.56) as opposed to those who had, who were overall younger (53.6 vs 56.5 years, p<0.001) and more likely to be members of patient organisations (34.4% vs 29.5%, p=0.023), receiving a higher quality of information on COVID-19 (3.0 vs 2.8 of 5, p=0.025), and being more likely to contact their rheumatologist during the pandemic (74.5% vs 55.5%, p<0.001). A multivariable logistic regression model showed that having a higher fear of adverse effects (OR= 1.96) and a lower hope of being vaccinated and protected against the virus (OR= 0.50) were associated with an unwillingness to be vaccinated in patients with non-inflammatory RMDs (OR= 2.03).
Finally, we found interesting the observation by Priori et al. (2021) that, compared to healthy controls, patients with RMDs who refused vaccination were more willing to reconsider their decision if they received more medical information. Indeed, in the REUMAVID cohort, not belonging to a patient organisation (OR= 1.44) or receiving poorer quality information (OR= 0.81) were associated with unwillingness to vaccinate. This was seen primarily in the sub-group of patients with non-inflammatory RMDs, whereas a higher proportion of patients with inflammatory articular RMDs (i.e., Axial Spondyloarthritis/Ankylosing Spondylitis, Gout, Peripheral Spondyloarthritis, Psoriatic Arthritis and Rheumatoid Arthritis) received information from patient organisations (58.9% vs 50.3% p=0.003) and reported themselves to be more likely to get vaccinated.
In conclusion, the results from phase 2 of the REUMAVID study show that the type of RMD, available treatments, source of information, and individual fears and hopes may condition the willingness to be vaccinated against COVID-19 among European patients with RMDs. Scientific societies and patient organisations have promoted the importance of vaccination in people with RMDs [6]. Therefore, patient organisations can play a crucial role as advocates and reliable sources of information for patients, especially in uncertain situations such as the current pandemic.
References
1. Priori R, Pellegrino G, Colafrancesco S, et al. SARS-CoV-2 vaccine hesitancy among patients with rheumatic and musculoskeletal diseases: A message for rheumatologists. Ann. Rheum. Dis. 2021. doi:10.1136/annrheumdis-2021-220059
2. Garrido-Cumbrera M, Marzo-Ortega H, Christen L, et al. Assessment of Impact of the COVID-19 Pandemic from the Perspective of Patients with Rheumatic and Musculoskeletal Diseases in Europe: Results from the REUMAVID Study (Phase 1). RMD Open 2021;7:e001546. doi:10.2139/ssrn.3734278
4. Andersen KM, Mehta HB, Palamuttam N, et al. Association Between Chronic Use of Immunosuppresive Drugs and Clinical Outcomes From Coronavirus Disease 2019 (COVID-19) Hospitalization: A Retrospective Cohort Study in a Large US Health System. Clin Infect Dis Published Online First: 7 January 2021. doi:10.1093/cid/ciaa1488
5. Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 1. Arthritis Rheumatol 2021;0:1–15. doi:10.1002/art.41734
6. Schulze-Koops H, Specker C, Skapenko A. Vaccination of patients with inflammatory rheumatic diseases against SARS-CoV-2: Considerations before widespread availability of the vaccines. RMD Open. 2021;7. doi:10.1136/rmdopen-2020-001553
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...
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).
Sir, we read with interest the recent communication by Priori et al. (2021) reporting that patients with rheumatic musculoskeletal diseases (RMDs) in Italy are less willing to receive the COVID-19 vaccination than healthy controls and that they are more likely to perceive themselves at higher risk of becoming infected with SARS-CoV-2 and developing severe COVID-19 [1]. These data are somehow at odds with our observations from patients with RMDs from other seven European countries who took part in the REUMAVID study [2].
REUMAVID is an international cross-sectional study using an online survey of unselected patients with 15 RMDs from seven European countries (United Kingdom, Spain, Italy, France, Portugal, Greece, and Cyprus). A total of 2,002 patients participated in the second phase between February and April 2021. At that time, the European Medicines Agency (EMA) had approved four COVID-19 vaccines: BioNTech Pfizer, Moderna, Oxford AstraZeneca, and Janssen [3]. Significant differences in the roll out speed and vaccine availability between countries contributed to global anxiety created by the rapid development of the vaccines. Like our Italian colleagues, we were keen to explore patients’ willingness to get the vaccination and factors associated with possible unwillingness to do so.
Contrary to the report by Priori et al. (2021), our results show that the majority of survey respondents were either willing to be (82.8%, n= 1,657) or had already been vaccinat...
Show MoreComment 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...
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