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People taking immunosuppressive drugs benefit significantly from SARS-CoV-2 vaccines approved in the United States to prevent and reduce the severity of COVID-19, according to the first study to quantify the vaccines' real-world effectiveness in this population.
Researchers' analysis of the electronic medical records of more than 150,000 people in the University of Michigan's healthcare system showed that even after becoming fully vaccinated, immunosuppressed individuals remain at higher risk for COVID-19 than are vaccinated people in the wider population who aren't receiving immunosuppressive therapy. However, they still derive benefit from vaccination, particularly when bolstered with a booster dose.
The study, published online in Annals of the Rheumatic Diseases, also claims to be the first to show that the Moderna (mRNA-1273) vaccine is as effective as the Pfizer-BioNTech (BNT162b2) vaccine for people taking immunosuppressants.
"Booster doses are effective and important for individuals on immunosuppressants," corresponding author Lili Zhao, PhD, told Medscape Medical News. "Previous studies focused mostly on the Pfizer vaccine, whereas our study is the first that also investigates the Moderna vaccine in a large, immunosuppressed population." Zhao is a research associate professor in biostatistics at the University of Michigan, Ann Arbor.
The epidemiologic study included 154,519 fully vaccinated and unvaccinated adults in the Michigan Medicine electronic health record database. Participants were considered fully vaccinated if they were within 2 weeks of having received a second dose of the Pfizer-BioNTech and Moderna vaccines or the single-dose Johnson & Johnson (Ad26.COV2.S) vaccine. The study population included 5536 immunosuppressed patients; of those, 4283 were fully vaccinated, and 1253 were unvaccinated.
The researchers focused on data collected from January 1 to December 7, 2021, so the study doesn't cover the Omicron variant. "The conclusions for immunosuppressed individuals are likely to remain the same during the Omicron period," Zhao said. "We are currently investigating this." Johnson & Johnson paused production of its vaccine in February.
The researchers found that among unvaccinated individuals, the immunosuppressed group had about a 40% higher risk of infection than did the immunocompetent patients (hazard ratio [HR], 1.398; 95% CI, 1.068 – 1.829; P = .0075) but a similar risk of COVID-19 hospitalization (HR, 0.951; 95% CI, 0.435 – 2.080; P = .9984). For the fully vaccinated, the gap was significantly wider: Immunosuppressed patients had more than double the risk of infection (HR, 2.173; 95% CI, 1.690 – 2.794; P < .0001) and almost five times the risk of hospitalization (HR, 4.861; 95% CI, 2.238 – 10.56; P < .0001), compared with immunocompetent patients.
However, among immunosuppressed individuals, the vaccinations significantly lowered risks compared to not being vaccinated. There was a statistically significant 45% lower risk of infection (HR, 0.550; 95% CI, 0.387 – 0.781; P = .001) and similarly lower risk of hospitalization that did not reach statistical significance (HR, 0.534; 95% CI, 0.196 – 1.452; P = .3724).
When those immunosuppressed patients received a booster dose, their protection against COVID-19 improved, compared with their immunosuppressed counterparts who didn't get a booster, with a 58% lower risk of infection after adjustment for age, gender, race, and Charlson Comorbidity Index (adjusted HR, 0.42; 95% CI, 0.24 – 0.76; P = .0037). The study included nearly 4 months of data after the Centers for Disease Control and Prevention recommended a booster dose of the Moderna and Pfizer-BioNTech vaccines for immunocompromised individuals in August 2021. Among the immunosuppressed patients, 38.5% had received a booster dose.
There also was no apparent difference in the effectiveness between the Moderna and Pfizer-BioNTech vaccines, with adjusted hazard ratios showing 41% to 48% lower risk of infection. Too few individuals in the study were vaccinated with the Johnson & Johnson vaccine to enable a sufficiently powered calculation of its effectiveness.
Other Studies Reach Similar Conclusions
The study findings fall into line with other studies of patient populations on immunosuppressants. A retrospective cohort study of Veterans Health Administration patients with inflammatory bowel disease who were taking immunosuppressants, published last year in the journal Gastroenterology, found that full vaccination with either Moderna and Pfizer-BioNTech vaccines was about 80% effective. Another retrospective cohort study of data from the National COVID Cohort Collaborative, published near the end of 2021 in JAMA Internal Medicine, reported that full vaccination significantly reduced the risk of COVID-19 breakthrough infection regardless of immune status. Immunosuppressed patients in this study had higher rates of breakthrough infections than immunocompetent patients, but the disparities were in line with what Zhao and the University of Michigan researchers report.
A review of 23 studies of COVID-19 vaccinations, published this month in Lancet Global Health, found that immunocompromised people ― 1722 of whom were included in the studies ― had lower rates of producing antibodies after two vaccine doses than did immunocompetent people, ranging from 27% to 92%, depending on the nature of their immunocompromised status; compared with 99% for the immunocompetent.
Strengths and Limitations
One strength of the Michigan study is the quality of data, which were drawn from the Michigan Medicine electronic health record, Zhao said. "So, we know who received the vaccine and who didn't," she said. "We also have access to data on patient health conditions, such as comorbidities, in addition to demographic variables (age, gender, and race), which were controlled in making fair comparisons between immunosuppressants and immunocompetent groups."
Alfred Kim, MD, PhD, an assistant professor of internal medicine and rheumatology at the Washington University in St. Louis, who was not involved with the study, credited Zhao and her team for delivering the first data that specifically quantified COVID-19 risk reduction in a large study population. Although he noted that the large sample size and the design reduced the chances of confounding and were strengths, he told Medscape Medical News that "lumping" the patients taking immunosuppressive drugs into one group was a weakness of the study.
"Clearly, there are certain medications (B-cell depleters, mycophenolate, for example) that carry the greatest risk of poor antibody responses post vaccination," he said. "One would have to guess that the greatest risk of breakthrough infections continues to be in those patients taking these high-risk medications."
Another possible problem, which the authors acknowledge, is spotty SARS-CoV-2 testing of study participants ― "a systemic issue," Kim noted.
"The easiest and most durable way to reduce the risk of getting COVID-19 is through vaccination, period," he said. "Now we have infection-rates data from a real-world study cohort to prove this. Furthermore, boosting clearly provides additional benefit to this population."
The National Institute of Allergy and Infectious Diseases provided funding for the study. Zhao, Zhao's co-authors, and Kim have disclosed no relevant financial relationships.
Ann Rheum Dis. Published online February 23, 2022. Full text
Richard Mark Kirkner is a medical journalist based in the Philadelphia area.
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Image 1: Michigan Medicine
Image 2: University of Washington at St. Louis
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Cite this: COVID Vax Effectiveness Quantified in Immunosuppressed Patients - Medscape - Mar 10, 2022.