With Rituximab, B-cell Counts Predict COVID-19 Vaccine Response

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Among multiple sclerosis (MS) patients on rituximab, higher B-cell counts are predictive of a better antibody-based response to a vaccine for COVID-19, according to a new Swedish study.

“In our study, the B-cell level in patients given Rituximab was the only factor that influenced the ability to form antibodies after vaccination,” Andreas Tolf, MD, a doctoral student at Uppsala University in Sweden and first author of the study, said in a press release.

“Previously, it was assumed that it was enough to wait a certain period after administering Rituximab for the vaccine to have a good effect. But to increase the chance of the vaccine causing the body to form antibodies, you first need to measure the level of B cells and ensure there are enough,” Tolf said.

According to the researchers, “for an optimal vaccine response … rituximab-treated patients with multiple sclerosis may be vaccinated as soon as possible, with rituximab treatment delayed until B-cell counts have reached at least [optimal levels].”

The study, “Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab,” was published in the journal JAMA Network Open.

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B-cells are immune cells best known for making infection-fighting proteins called antibodies. B-cells play a critical role in protecting the body from infectious threats — of particular relevance, they can make antibodies that bind to viruses like SARS-CoV-2 (which causes COVID-19), stopping the virus from infecting cells. However, B-cells also contribute to the inflammation that drives MS.

Rituximab, a medication that works to deplete B-cells, is the most commonly used MS treatment in Sweden. Though it is not approved for use in MS, it is commonly used off-label as a treatment for this condition; other medications with a similar mechanism of action have been approved for MS.

Vaccines for COVID-19 work by promoting an immune response against the virus, including — critically — the production of antibodies against SARS-CoV-2. But since rituximab is designed to lower B-cell levels, patients on this therapy may be less able to mount an immune response following vaccination.

“Although a body of literature on [immune] responses after vaccination against SARS-CoV-2 in patients with MS treated with B-cell–depleting agents emerged in the previous year, it is still unknown which factors are most important for an adequate vaccine response,” the researchers wrote.

To learn more, the scientists evaluated levels of antibodies against SARS-CoV-2 in 67 MS patients on rituximab. All had received Comirnaty (tozinameran), the vaccine developed by Pfizer/BioNTech, given at the standard two doses about three weeks apart. Among the patients, 82% were women, and 73% had relapsing-remitting disease. The mean age was 43.

“The purpose of the present study was to investigate which factors were associated with a favorable vaccine response after vaccination with tozinameran for protection against COVID-19 disease,” the scientists wrote.

Results showed that, after receiving the vaccine, more than one-quarter of the patients (28%) had antibody levels in response that were predicted to be too low to confer protection against COVID-19.

The scientists conducted statistical tests to look for factors associated with an increased likelihood of having antibody levels high enough to confer protection. The only factor that was statistically significant was B-cell levels at the time of vaccination.

“Our multivariate regression analysis indicated that B-cell counts were the most decisive factor for an adequate [antibody] response” for MS patients on rituximab for the COVID-19 vaccine, the researchers concluded.

Specifically, the team proposed a cut-off of 40 B-cells per microliter of blood, which was found to accurately predict the generation of protective antibodies in up to 9 of each 10 patients. The team suggested that, for MS patients on rituximab, “an additional vaccine dose may be considered when the B-cell count reaches 40/[microliter] to ensure that as many patients as possible will generate an adequate vaccine response.”

According to Anna Wiberg, a researcher in clinical immunology at Uppsala University, “There was a threshold with a level of B cells at 40/[microliter] or more where 90 percent formed protective levels of antibodies.”

The scientists noted that, while B-cell levels tend to increase over time since the last infusion of rituximab, rates of B-cell recovery varied markedly from patient to patient.

“Our data showed a large interindividual variability in the rate of B-cell recovery. … This calls into question the general recommendation of performing vaccinations 3 to 6 months after the last infusion of a B-cell–depleting agent,” the team wrote. “Instead, relying on the measurement of B-cell counts appears to be the rational approach and is feasible in many hospital settings.”

In terms of safety, no unexpected findings, severe MS-associated disease activity, or cases of COVID-19 infection were reported after vaccination.

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