Dampened Response to COVID-19 Vaccines in Rituxan-Treated Patients with MS May Improve with Extended Dosing Intervals

A study by Kaiser Permanente researchers found that the overall the risk of COVID-19-related hospitalization was low in vaccinated individuals with multiple sclerosis, regardless of whether participants had received Rituxan treatment. But spacing out vaccination may offer added protection against COVID-19.

Rituxan (rituximab) is a monoclonal antibody indicated for the treatment of several B-cell-mediated conditions, including non-Hodgkin’s lymphoma, leukemia, and rheumatoid arthritis. It is used off-label as a treatment for multiple sclerosis (MS)≥

Rituxan exerts its effect by targeting and binding to the CD20 antigen on the surface of B cells, resulting in B-cell depletion. Studies have found that humoral-mediated (B-cell mediated) immune responses to COVID-19 vaccines are dampened in MS patients who receive B-cell-depleting treatments, such as Rituxan. In studies, this was more evident in individuals who received vaccines within 6 months of their last B-cell-depleting treatment versus those who were vaccinated at least 6 months after their last infusion.

Jessica B. Smith, M.P.H., a Kaiser Permanente researcher, and her colleagues studied whether treatment with Rituxan might reduce the efficacy of the COVID-19 vaccines.

In a retrospective cohort study published in JAMA last month, lead author Jessica B. Smith, M.P.H., in the Southern California Permanente Medical Group’s research and evaluation department, and colleagues investigated whether COVID-19-vaccinated patients with MS who received Rituxan had an increased risk of COVID-19-related hospitalization. Furthermore, if this were so, Smith and colleagues sought to determine whether holding off on vaccination for longer than 6 months after Rituxan treatment lowers this risk.

The researchers gathered data from Kaiser Permanente Southern California’s complete electronic health records from Jan. 1, 2020 through Feb. 15, 2022. Participants included nearly 4,000 patients diagnosed with MS who received two COVID-19 mRNA vaccines or one viral vector vaccine and a booster dose. The primary outcome was hospitalization due to COVID-19.

The study found that, overall, the risk of COVID-19-related hospitalization was low in vaccinated individuals regardless of whether participants had received Rituxan treatment. However, the risk was higher in Rituxan-treated patients compared with those who received non-B-cell-depleting disease-modifying therapies or no treatment.

The authors note that normal humoral response to COVID-19 vaccines requires B-cell counts of at least 40 cells per microliter (µL) of blood, and a diminished response was seen when B-cell counts dropped below this level.

Given the low overall risk of hospitalization in vaccinated individuals, the authors recommend that the increased risk observed in patients treated with Rituxan may be reduced by administering COVID-19 vaccines according to public health guidelines but increasing dosing intervals to greater than 6 months to allow for B-cell levels to rise above 40/µL before vaccine administration.

“The low risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS receiving rituximab should not preclude rituximab use,” wrote Smith and her colleagues. “Instead, expanding access to SARS-CoV-2 vaccines for individuals receiving rituximab therapy in low- and middle-income countries should be prioritized.”