Rituximab for AAV Linked to Poor Responses to COVID-19 Vaccines

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Treatment with the CD20 inhibitor rituximab is significantly associated with poor antibody responses to COVID-19 vaccines among people with ANCA-associated vasculitis (AAV), a study found.

However, the number of antibody-producing B-cells, the rituximab dose, and the timing between last rituximab administration and vaccination were all important factors determining how likely a patient is to develop antibodies following the COVID-19 vaccine.

“On the basis of these findings it is reasonable to propose that [antibody-producing B-cell] counts can be used as a marker to aid decisions on timing and anticipated response to other vaccines in patients receiving rituximab,” the researchers wrote.

The study, “SARS-CoV-2 Vaccine Response in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis,”  was published in the journal Kidney International Reports.

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In AAV, self-reactive antibodies, called anti-neutrophil cytoplasm antibodies (ANCAs), bind to and over-activate immune cells called neutrophils. This triggers an immune response that ultimately damages small blood vessels in multiple organs.

To manage these excessive immune reactions, AAV patients are often prescribed medications that suppress the immune system. Rituximab, sold as Rituxan among others, is an antibody-based therapy that binds to and eliminates the CD20 receptor on the surface of B-cells, the immune cells that produce antibodies.

Because immunosuppressive medications dampen immune responses, patients who receive these therapies may be at a higher risk of severe COVID-19 outcomes and may have poorer responses to vaccines. In line with this, recommendations for the use of immunosuppressive therapies, such as rituximab, and the timing for COVID-19 vaccination in AAV patients were published earlier this year.

In the recent study, a team of researchers in the U.S., U.K., and Germany searched for associations between treatment with immunosuppressive medications in AAV and the presence of antibodies against SARS-CoV-2, the virus that causes COVID-19.

A total of 159 AAV patients, whose levels of antibodies were measured between March and August, a mean of 50 days after their second vaccine dose (or first for those who got the Johnson & Johnson vaccine), were included in the analyses.

Their mean age was 65.5, and the average time from diagnosis of AAV was seven years.

The majority of patients (97%) received full immunization with one dose of the Johnson & Johnson (3.1%) or both doses of the Oxford-AstraZeneca (21.4%), Pfizer-BioNTech (56%), or Moderna (19.5%) vaccines.

Over half of patients (55%) produced anti-SARS-CoV-2 antibodies. The researchers found no relationship between the production of antibodies and age, sex, race, ANCA type, type of vaccine received, co-morbidities (additional disorders), or kidney problems.

At the time of their vaccination, 144 patients were on immunosuppressive medications. Among those, 129 were receiving rituximab, and half developed anti-SARS-CoV-2 antibodies. Additional analyses found that rituximab use was associated with a 69% greater likelihood of not developing antibodies, and this poor antibody response was particularly evident if treatment was given within six months before the first vaccine dose.

The subset of B-cells that produces antibodies is often identified with the CD19 marker. In theory, the greater the number of CD19-positive B-cells, the more likely a person is to develop an antibody-based response to the COVID-19 vaccines.

Among the study participants, 107 had their CD19 counts (number of CD19-positive cells) measures around the time of vaccination. Statistical analysis revealed that patients with measurable CD19 counts were almost 30 times more likely to respond to vaccination.

The cumulative dose of rituximab and the time to last rituximab dose also had a significant effect on antibody production in response to COVID-19 vaccination.

For every 1 gram increase in cumulative rituximab dose before vaccination, there was a 10% reduction in the chance of developing anti-SARS-CoV-2 antibodies. For every month between rituximab treatment and vaccination, the rate of antibody-positive patients increased by 8%.

However, CD19 counts were the best predictive marker for a positive antibody response to COVID-19 vaccines, independent of the cumulative dose or time from last rituximab administration.

A few study limitations were highlighted by the researchers, including not having investigated the T-cell response, a key component of the immune system, and the relatively small sample size.

“Despite this, our study cohort represents the so far largest study on humoral [antibody] response to COVID-19 vaccine in AAV patients, the majority of whom were treated with B cell depleting therapy,” the researchers wrote.