PHILADELPHIA—Patients with rheumatic diseases often mount an adequate immune response after receiving COVID-19 vaccinations, but that is not always the case, and certain medications make patients more prone to having an insufficient response, said Judith James, MD, PhD, chair, Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, at an ACR Convergence 2022 session.
The assessment of the patterns of vaccination responses in these immunosuppressed patients came in a session taking stock of lessons learned during the COVID-19 era.
Not as Robust of a Response
Dr. James said that the explosion of research into COVID-19 vaccination responses among patients on immunosuppressive medications has made it clear that some patients taking methotrexate, mycophenolate mofetil (MMF), B cell-depleting agents and, often times, abatacept, do not mount as strong of a response as other patients.
“We see this in study after study,” she said, cautioning that data on COVID-19 and vaccinations can become outdated quickly.
More generally, she said, “Even though many of our patients make responses, they usually don’t make responses as robust as seen in healthy individuals.”
In a recent meta-analysis of these cases, researchers found that responses for those on immunomodulatory drugs were lower than healthy controls, that a two-dose regimen of messenger RNA (mRNA) vaccine was associated with a better response, and that anti-CD20 and anti-CTLA4 drugs were associated with a weaker response.1 Researchers also concluded that assessing seroconversion might be necessary in certain patients and that vaccination schedules need to be individualized depending on someone’s underlying immunosuppressive drug and their current treatment.
Another study from earlier this year found that patients treated with methotrexate, abatacept and Janus kinase inhibitors tended to have a response similar to healthy controls after a third vaccination, and those on glucocorticoids, MMF and rituximab tended still to have weaker responses.2
Other studies have found that pausing methotrexate and having a longer time since the last anti-CD20 antibody infusion can help with the response to a COVID-19 booster.3,4
An observational, multi-center study of 544 patients by the National Institute of Allergy and Infectious Diseases-funded Autoimmunity Centers of Excellence found a much higher rate of non-response to COVID-19 boosters among those who had not previously had a COVID-19 infection—a 37% non-responder rate after the first series of COVID-19 vaccinations and a 24% non-responder rate after the booster. If patients had previously had COVID-19, the non-responder rate was just 5% to 7%.
In another study by the same group, patients had their MMF or mycophenolic acid (MPA) held for three days before and ten days after their shots, and weekly methotrexate held for seven days before and seven days after. Patients on B cell-depleting therapy continued their medications. With 141 mRNA-vaccinated patients, researchers saw that many, but not all, on B cell-depleting agents mounted little or no response, and those on MMF/MPA or methotrexate tended to mount a response, but in many cases, the response was not as intense as healthy controls and quickly waned.
They found that some breakthrough infections occurred after the booster shot, but the rate was comparable to other patients with autoimmune rheumatic diseases.
T Cell Responses
On an encouraging note, Dr. James pointed to the finding that even those on B cell-depleting therapy who don’t make an antibody response to the vaccine tend to mount responses that seem to be protective, given that breakthrough infection rates were similar to those reported for patients not on such therapy.
“Even the patients who are on B cell-depleting therapy tend to make T cell responses,” she said. “The initial COVID vaccination series is inducing a T cell response in close to 70% of patients on B cell-depleting therapy.”
Asked whether those who have a poor serologic response are still protected from severe COVID-19 that can be tracked to a T cell response, Dr. James said that more data is being generated, but that it appears that that is the case at least in some patients.
“The initial work suggests that there are adequate numbers as well as a robust interferon response, and so it looks like the T cell response—it may not be the equivalent of [healthy people], but is substantial enough that we usually see infections that are milder in our vaccinated autoimmune disease patients compared to non-vaccinated.”
Despite the enormous amount of data generated about COVID-19 and vaccinations among the immunosuppressed, plenty still needs to be investigated, she said.
“We have many questions remaining, including things that you think we would know the easy answer to, like what exactly is a protective response,” especially for newer variants, Dr. James said.
Clinicians, she said, also await answers on how patients respond to the new bivalent vaccine, when effective antibody and T cell responses start to diminish, who is at risk for mild post-vaccination autoimmune disease flares, what happens to responses with frequent vaccinations and boosters, and what impact monoclonal antibody treatment has on booster responses.
Unanticipated Pandemic Benefits
Despite the misery of the pandemic, she pointed to some positives that have come out of the experience, including the knowledge about effectiveness and timely generation of messenger RNA vaccines and the explosion of data about vaccination in adults and autoimmune disease patients, “which I think is very interesting and exciting, and I think we’re going to learn a lot about vaccination responses in individuals with healthy and with dysregulated immune systems.”
Education in the community has also increased.
“Everybody is interested in immunology now,” she said. She also pointed to more understanding about the barriers to vaccination and potential solutions.
“There are things we have learned and are learning in autoimmune disease vaccination, post-infection autoimmunity and effects of further perturbation of the autoimmune disease patient’s dysregulated immune system after infection,” she said, “that never would have been studied before.”
Thomas Collins is a freelance medical writer based in Florida.
- Jena A, Mishra S, Deepak P, et al. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis. Autoimmun Rev. 2022 Jan;21(1):102927.
- Hadjadj J, Planas D, Ouedrani A, et al. Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases. Ann Rheum Dis. 2022 May;81(5):720–728.
- Abhishek A, Boyton RJ, Peckham N, et al. Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): A randomised, open label, superiority trial. Lancet Respir Med. 2022 Sep;10(9):840–850.
- Jyssum I, Kared H, Tran TT, et al. Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: A prospective, cohort study. Lancet Rheumatol. 2022 Mar;4(3):e177–e187.