Year: 2023
Type: letter
Abstract: We have carefully read the Letter to the Editor written by Kleebayoon and Wiwanitkit [1] regarding our recently published study “Association between COVID-19 vaccination and myasthenia gravis: a population-based nested case control study” in the European Journal of Neurology [2]. The authors raised concerns about limitations and biases which are common to all observational studies, and are discussed in our article [2]. Kleebayoon and Wiwanitkit stated that a valid comparison necessitates further adjustment for potential confounders. However, they did not specify any confounders. We selected confounders based on their known association with both COVID-19 vaccine (exposure) and myasthenia gravis (MG) (outcome). There are no identifiable causes for MG except for an association with age, sex, and genetic predisposition [3]. Therefore, cases and controls were matched on age, sex, and calendar time, while the multivariable model also included ethnicity, prior COVID-19 infection, and socioeconomic status. We have now conducted another analysis with additional adjustments for smoking, obesity, diabetes, hypertension, ischemic heart disease, heart failure, prior stroke, peripheral vascular disease, atrial fibrillation, prior cancer, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple sclerosis, hypothyroidism, and hyperthyroidism [4], obtaining the same results with odds ratios (ORs) of 1.13 (95% CI 0.72–1.76) for new-onset MG and 1.41 (95% CI 0.36–5.52) for MG exacerbation. Kleebayoon and Wiwanitkit stated “The study did not take into consideration the distribution of COVID-19 vaccination type or dosage received by study participants”. We would like to direct the authors to our article, where they can find that approximately 99% of the administered vaccines were Pfizer-BioNTech vaccines. Furthermore, the distribution of the particular vaccine dosage among both cases and controls, together with its association with new-onset MG and MG exacerbation, is detailed in our article and in the supplementary tables 1–3 and tables 5–10 [2]. The authors stated that large multicenter trials are required to investigate relationships between vaccines and diseases. While randomized clinical trials are regarded as the gold standard for assessing vaccine outcomes, they are usually limited by their sample size particularly when attempting to detect rare events. This is where postmarketing surveillance, relying on observational studies, becomes necessary. During 2021, the overall estimated incidence of MG in the United States stood at 3.2 per 100,000 individuals and displayed an upward trend with advancing age, reaching 10.2 per 100,000 among individuals aged ≥65 years [5]. Given the rarity of MG, clinical trials are not a reasonable choice for investigating the relationship between COVID-19 vaccines and MG. While the authors did not find the number of MG cases in our study impressive, it is important to note that these incident cases emerged within a cohort of over 3 million adults followed over 18 months. In their Letter to the Editor, Kleebayoon and Wiwanitkit [1] shared other ideas, such as “the immune system's reaction to vaccine may differ depending on how it reacts to specific genetic features”. Undoubtedly, this is interesting. We hope that gene sequencing data will become available within population-based registries in the future, leading to a more profound understanding in this field. Anat Arbel: Conceptualization (lead); writing – original draft (lead). Haya Bishara: Writing – review and editing (equal). Ofra Barnett-Griness: Formal analysis (lead); investigation (equal); data curation (equal). Shai Cohen: Writing – review and editing (equal). Ronza Najjar-Debbiny: Writing – review and editing (equal). Naomi Gronich: Writing – review and editing (equal). Eitan Auriel: Writing – review and editing (equal). Walid Saliba: Conceptualization (lead); writing – original draft (lead); formal analysis (lead); data curation (lead); supervision (lead). Eitan Auriel received honoraria from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison. All other authors report no potential conflicts of interest. Individual level data cannot be made publicly available due to legal restrictions.
Source: European Journal of Neurology
DOI: 10.1111/ene.16087
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,940
OpenAlex ID: W4387380673