Fourth COVID-19 vaccine dose reduces severe infection risk by 65% in patients with SARDs
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SAN DIEGO — A fourth COVID-19 mRNA vaccine dose reduces the risk for severe infection by 65% in patients with systemic autoimmune rheumatic disease using immunomodulators, according to data presented at ACR Convergence 2023.
“It is well known that patients with systemic autoimmune rheumatic diseases using [disease-modifying antirheumatic drugs (DMARDs)] do not respond as robustly to vaccination, including COVID-19 vaccination, as patients who are not using immunomodulators,” Jennifer Hanberg, MD, of Massachusetts General Hospital, told Healio. “Despite this, there is evidence that the primary COVID-19 vaccine series — defined as three doses — does reduce adverse outcomes and infection rates in patients using DMARDs.”
However, less is known about uptake, and the utility, of a fourth COVID-19 vaccine dose, she added.
“COVID-19 vaccination recommendations have evolved quickly over the last few years, and the CDC recommended a fourth dose for immunocompromised patients in the fall of 2021,” Hanberg said. “Prior to our study, there had been relatively little formal investigation into the effectiveness of this fourth dose among patients with systemic autoimmune and rheumatic diseases using DMARDs.”
To examine the effectiveness of a fourth COVID-19 vaccine dose in patients with systemic autoimmune rheumatic diseases who are using immunomodulators, Hanberg and colleagues conducted an emulated target trial in a large U.S. health care system. All 4,010 participants had been diagnosed with a systemic autoimmune rheumatic disease and were using immunomodulating drugs. Among these patients, 2,994 received a fourth COVID-19 vaccine dose — either BNT162b2 or mRNA-1273 — between Jan. 16, 2022, and June 11, 2022. Meanwhile, 1,014 patients who were eligible for a fourth dose, but did not receive it, were assessed as comparators.
The primary outcome was COVID-19 infection. Follow-up was conducted through COVID-19 infection; bivalent vaccine availability, on Sept. 9, 2022; deviation from the assigned arm, such as receiving a fifth dose for those in the study arm, or a fourth dose for comparators; or non-COVID death. The researchers used logistic regression to calculate the propensity score (PS) for receiving the fourth dose on a weekly basis. In addition, they performed time-stratified, overlap PS-weighted Cox regressions to assess the association between a fourth dose and the risk each outcome.
According to the researchers, the incidence of COVID-19 infection in the fourth-dose group was 14.8 cases per 1,000 person-months, compared with 23.7 per 1,000 person-months among comparators. This resulted in a rate difference between the two cohorts of –8.85 (95% CI, -13.37 to -4.33), and an HR of 0.59 (95% CI, 0.47-0.74) per 1000 person-months favoring the vaccination group. Individuals in the fourth dose group also were less likely to experience hospitalization or death due to COVID-19 within 14 days of infection — 0.36 vs. 0.93 events per 1,000 person-months (HR = 0.35; 95% CI, 0.14-0.85).
“We found a significant protective effect from the fourth vaccine dose among patients with systemic autoimmune and rheumatic diseases using DMARDs,” Hanberg said. “The fourth vaccine dose was also associated with a decreased risk of severe COVID-19, defined as hospitalization or death within 2 weeks of a SARS-CoV-2 infection.
“It will be necessary to understand the effect of additional doses, including the bivalent vaccine and the XBB.1.5 vaccines that were deployed this fall,” she added. “There are also subgroups of patients using particular DMARDs, including B-cell depleting therapies such as rituximab [Rituxan, Genentech], in whom the effectiveness of these doses needs to be further investigated.”
According to Hanberg, the reality of vaccine hesitancy and related conversations between patient and provider should be considered by every rheumatologist.
“Our data may be informative in these conversations,” she said. “Our findings support the recommendation that patients with systemic rheumatic disease should stay current with their COVID-19 vaccination series.”
Ongoing COVID-19 vigilance from rheumatologists is critical in the next stages of the pandemic, Hanberg said.
“Even in the current wave of the pandemic, where severe COVID-19 is relatively rare, our patients remain vulnerable to adverse outcomes from this virus,” she said. “Our study provides evidence that, beyond the primary thee-dose series, a fourth dose of mRNA vaccine reduces the risk for SARS-CoV-2 infection and severe COVID-19 disease in patients using DMARDs. Although the public health emergency has been declared over, as providers we are still responsible for making sound recommendations for preventive care relating to the immunosuppression we prescribe, and we should continue to recommend an up-to-date vaccination series for immunosuppressed patients.”
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Hanberg J. Abstract 2564. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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