Kyriakos A. Kirou, MD, DSc, FACP: COVID-19 Vaccine Antibody Responses in Patients Treated With B-Cell Agents

Rheumatology Network interviewed Kyriakos A. Kirou, MD, DSc, FACP, to discuss the key findings of his upcoming ACR presentation, “COVID-19 Vaccine Antibody Responses in Patients Treated with B-Cell Agents Depend on B-Cell Counts at Time of Vaccine.” Kirou is a rheumatologist at Hospital for Special Surgery.

Rheumatology Network: Why are patients with systemic rheumatic diseases unable to achieve adequate immune responses to the COVID-19 vaccine? 

Kyriakos A. Kirou, MD, DSc, FACP: Patients with systemic rheumatic diseases are unable to achieve adequate immune responses to the COVID-19 vaccine primarily because of their treatments with immunosuppressive medications. Some of the medications are particularly strong in suppressing the immune system and therefore, responses to vaccines. These include rituximab, which targets primarily B-cells which are directly involved in antibody production. Other stronger immunosuppressive medications include mycophenolate mofetil, azathioprine, and methotrexate, which target the whole immune system, and therefore both B- and T-cells. Of course, the level of immunosuppression also depends on the doses of these medications. Some other medications have little or no effect in immune responses, but they are still helpful for the disease. These include hydroxychloroquine and sulfasalazine. In addition to immunosuppressive medications, the disease itself, especially when it is very active, might not allow optimal responses to vaccines.

RN: Can you give me a bit of background on the study design your team utilized? 

KK: This study is in effect, a real-life observation of patients in my practice that received the COVID-19 vaccination. We retrospectively looked at patients that had received one of the approved COVID-19 vaccines and studied their IgG antibody responses to the spike protein of this SARS-CoV-2 virus by one of the commercial assays available. We particularly focused on one of the assays to achieve uniformity of the data for our analysis. We had 60 patients that fulfilled those criteria. The majority of the patients, almost half of them, were patients with SLE (lupus). Given the strong effect of rituximab, a B-cell targeting agent in blocking immune responses to the vaccines, we also looked at absolute numbers of B-cells in the blood of patients around the time of the vaccination. We hypothesized that the number of B-cells present in the circulation at the time of vaccination would be an important factor in determining antibiotic responses to the vaccines. We also looked at another lupus medication, belimumab, which also targets B-cells. This medication does not kill B-cells directly like rituximab does, but inhibits their proliferation and survival. B-cell numbers in patients taking belimumab are not zero or undetected but often very low.

RN: What are the results of this study?

KK: We found that patients treated with either rituximab and/or belimumab indeed had lower antibody responses to the vaccines. We were impressed by the finding that the lower the B-cells the more likely that the responses would be low. This was independent of the B-cell targeting medication and happened in both patients on rituximab and patients on belimumab. We were unable to find lower antibody responses in patients that received other immunosuppressive medications or biologics, probably because of the limited number of patients in our study. We also observed somewhat better response to the Moderna vaccine compared to Pfizer BioNTech vaccine.

RN: What is the clinical significance of these results?

KK: We believe these results should help physicians treating patients with systemic rheumatic diseases, such as lupus, to optimize antibody responses of their patients to the vaccines. With regard to patients on rituximab, if the disease is stable and allows some delay, waiting until the B-cell number comes up to above zero, would be helpful to allow response to the vaccine. However, if the disease is very active and cannot afford delaying rituximab treatment, they should proceed with the COVID-19 vaccination anyway. It is possible even without full antibody response that they will still have some protection from T-cell responses. With regard to patients on belimumab, measuring B-cells in the circulation could predict whether someone would respond well or not to the vaccine. For patients that receive combination treatment with another agent such as mycophenolate mofetil or methotrexate in addition to belimumab, holding that other medication around the time of the vaccine should help improve antibody responses. Holding belimumab before and after vaccination might also help. However, we do not know for how long before or after the vaccine belimumab should be held in order to allow a better response. Again, disease activity and severity should be taken into consideration to assess risk and benefit before holding any of these medications.

RN: Is your team planning on doing any further research on this topic?

KK: We are now looking at the effect of modifications of immunosuppressive medications around the time of vaccine or booster COVID-19 vaccines, to have a better understanding of how to optimize these responses.

RN: What are you most looking forward to in the upcoming ACR conference?

KK: We will be looking at my colleagues’ studies and their findings for more insights. This is a collective effort by the whole rheumatology community.

RN: What is the biggest challenge facing rheumatologists today?

KK: The biggest challenge with regard to the pandemic and treating patients with systemic autoimmune rheumatic disease is to control the disease while protecting the patient from getting COVID-19. This may require fine-tuning of dosage/timing of immunosuppressive medications around vaccinations in order to optimize humoral (antibody mediated) responses and protection from COVID-19 while maintaining good control of the underlying disease.