COVID-19 vaccine response drops significantly after 6 months in patients with IMIDs
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Key takeaways:
- Researchers reported being concerned that rituximab had “strong effects” on lowering post-vaccination immune response.
- The findings may aid decision-making and lead to personalized vaccine strategies.
COVID-19 antibodies are significantly reduced by 6 months post-vaccination among patients with immune-mediated inflammatory diseases, according to data published in The Journal of Rheumatology.
However, individuals with diseases such as rheumatoid arthritis and systemic lupus erythematosus continued to see positive impacts to immunogenicity with fourth and fifth doses of COVID-19 vaccines, the researchers wrote.
“Currently, individuals with immune-mediated inflammatory diseases (IMIDs) may be unsure about the value of COVID vaccination beyond the primary series,” study author Sasha Bernatsky, MD, PhD, of McGill University, in Montreal, told Healio. “This is particularly concerning since immunosuppressant therapy may put individuals at higher risk for SARS-CoV-2 transmission.
“On the other hand, social ‘vaccine fatigue’ has caused many individuals to decline additional COVID boosters after the primary series,” she added. “Since COVID-19 infection is a potentially fatal and vaccine-preventable co-morbidity, it is vital that individuals with IMIDs have access to relevant information that will help them decide when to get their next COVID vaccination.”
To examine how time since last vaccination impacts serologic responses to COVID-19 vaccination and infection in patients with IMIDs, Bernatsky and colleagues conducted a study of 1,823 adults (mean age, 53.2 years) with various relevant conditions. The cohort was recruited from eight cities across Canada beginning in early 2021. Dried blood spots or sera, as well as self-reported data, were collected at enrollment, then 2 to 4 weeks, and subsequently 3, 6 and 12 months, post-vaccination. Participants either collected dried blood spots at home and mailed them for analysis, or had sera analyzed at local centers, depending on their location.
Samples underwent automated enzyme-linked immunosorbent assays to measure log-transformed anti-receptor-binding-domain (RBD) titers and anti-nucleocapsid IgG. The effects of each covariate on anti-RBD titers were expressed as exponentiated beta coefficients.
According to the researchers, log-transformed anti-RBD titers were positively associated with female sex, number of vaccine doses, self-reported COVID-19 infections between 2021 and 2023, and negatively associated with use of prednisone, anti-TNF agents and rituximab (Rituxan, Genentech) — either the originator or biosimilars. Titers were also negatively associated with time since last vaccination, especially beyond 210 days (exponentiated coefficient = 0.88; 95% CI, 0.8-0.95).
Vaccine doses four and five were associated with positive effects on anti-RBD serology, the researchers wrote.
“Our data suggest that these individuals should continue to consider additional doses when more than 6 months has elapsed since last vaccination or infection,” Bernatsky and colleagues wrote.
Bernatsky said she was “a bit surprised” that rituximab demonstrated “such strong effects” (adjusted exponentiated coefficient = 0.23; 95% CI, 0.1-0.53) on lowering post-vaccination immune response, despite the cohort containing only 44 patients on rituximab.
“However, this is a fairly robust finding across studies, so it is something we need to pay attention to,” she told Healio.
“These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when more than 6 months have elapsed since last COVID vaccination/infection,” she added.
Bernatsky highlighted further research to be done in this area.
“The intricate relationships between all these variables — age, sex, race/ethnicity, number and timing of vaccination, type of vaccinations, past medical history and the details of medications received — need to be carefully modelled for us to truly understand if we can ‘personalize’ vaccine decisions,” she said. “That is, can we offer strategies tailored to each patient’s needs?”
According to Bernatsky, the current analyses considered medication exposures only at the time the subject enrolled in our study.
“We would like to undertake more detailed analyses of past medications and doses in order to identify those with higher or lower immune system responses to vaccination,” she said. “The ultimate goal is to prevent COVID-related infections, hospitalizations and deaths.
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
COVID-19 remains endemic in the United States, exhibiting four times the hospitalization rate and twice the death rate of influenza. There has been significant interest in immune-mediated inflammatory diseases (IMIDs) in relation to COVID-19.
Individuals with IMIDs have an increased susceptibility to COVID-19 infection and experience more severe and prolonged symptoms. For veterans with rheumatoid arthritis treated with prednisone and biologic or targeted synthetic DMARDs, the risk for COVID-19 infection was 66% higher, while the risk of COVID-19 related hospitalization or death was 112% higher, compared with those without RA. This heightened risk for severe COVID-19 in patients with IMIDs is associated with certain immunosuppressive therapies, including rituximab (Rituxan, Genentech), Janus kinase inhibitors and glucocorticoids.
Additionally, 40% of patients with IMID experience flares related to COVID-19 infection, likely due to the interruption of their IMID therapy. COVID-19 vaccine seroconversion occurs in approximately 80% of patients with IMID, but this drops to less than 70% for those on B-cell depleting therapy and glucocorticoids. Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology recommend administering supplemental mRNA vaccine doses after the initial three-dose primary series to elicit stronger immune responses in the IMID population.
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