Which COVID-19 vaccine should SARDs patients on immunomodulators use?

Vaccination with either BNT162b2 or mRNA-1273 results in a comparable risk of breakthrough COVID-19 infection among patients with systemic autoimmune rheumatic diseases (SARDs) using immunomodulatory medication, a study has shown.

“The choice of mRNA vaccine type is unlikely to strongly influence the risk of breakthrough infection in this population and the decision regarding which mRNA vaccine to receive should be based on availability rather than potential difference in effectiveness,” the researchers said.

A total of 9,838 patients with SARDs being treated with disease-modifying antirheumatic drugs (DMARDs) or glucocorticoids in the Mass General Brigham healthcare system who received either BNT162b2 or mRNA-1273 as their initial vaccine series were included in the study. They were followed until positive SARS-CoV-2 test, death, or 22 February 2022.

The researchers then used time-stratified, overlap propensity score (PS)-weighted Cox proportional hazard models to compare the risk of breakthrough COVID-19 infection between BNT162b2 or mRNA-1273 vaccine recipients.

Both vaccine groups had similar demographic and clinical characteristics after overlap weighting (mean age 61 years, 75 percent female, 52 percent with rheumatoid arthritis, 74 percent receiving conventional synthetic DMARDs, and 43 receiving biologic DMARDs). [J Rheumatol 2023;50:697-703]

Of the patients, 5,516 received BNT162b2 and 4,322 mRNA-1273 vaccine. The number of breakthrough infections was 446 and 329, respectively, and the corresponding time-stratified PS-weighted rate difference was 0.71 (95 percent confidence interval [CI], ‒0.70 to 2.12) per 1,000 person-months (hazard ratio [HR], 1.12, 95 percent CI, 0.90‒1.39).

Notably, when follow-up was cut prior to the Omicron variant wave, a trend toward higher breakthrough risk was observed with BNT162b2 than with mRNA-1273 (weighted HR, 1.34, 95 percent CI, 0.91‒1.98).

“There may be a benefit to mRNA1274 over BNT162b2, but this was substantially blunted in a time period characterized by Omicron dominance,” the researchers said.

Blunted immune response

Earlier studies reported some immunomodulator users to have a blunted humoral immune response to SARS-CoV-2 vaccines, including BNT162b2 and mRNA-1273, and such poor response can result in a higher risk of breakthrough infection. [Curr Opin Pharmacol 2022;65:102243]

“Our study expands upon prior findings by estimating similar effectiveness of both currently available mRNA vaccines on the risk of breakthrough infection,” the researchers said. “However, our study may have been too small to detect modest statistically significant differences between the vaccine types.”

Another study that examined the efficacy of COVID-19 vaccines in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease found that mRNA-1273 appeared superior to BNT162b2. [Lancet Rheumatol 2022;4:e430-40]

Several factors differentiate the current analysis, such as the extended follow-up to include a time period characterized by the Omicron variant dominance and the focus on the risk of breakthrough infection between vaccine types rather than vaccine efficacy, among others. [MMWR Morb Mortal Wkly Rep 2021;70:1731-1734]

“Patients with SARDs initiating the vaccine series should be encouraged to receive whichever mRNA vaccine is available,” the researchers said.