COVID boosters in AIIRD

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study.

COVID-19 is the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It was declared a pandemic by the World Health Organization in March 2020. Vaccination against SARS-CoV-2 is important to help prevent disease, but it is necessary to understand the long-term vaccine-induced immunity in different groups of people, such as those with an autoimmune inflammatory rheumatic disease (shortened to AIIRD). 

There are many types of AIIRD. This includes types of inflammatory arthritis that affect a person’s joints, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and lupus. Some studies have suggested that vaccines might not work well in people with rheumatic diseases. This might be because of underlying changes in a person’s immune system with these kinds of diseases, or could be due to treatment with anti-rheumatic drugs which also have an impact on the immune system. 

Because of the resurgent COVID-19 outbreak, administration of a third mRNA vaccine dose (booster) was approved by regulatory authorities. However, there is only limited information on the response to a second or third dose of the mRNA COVID vaccine made by Pfizer and BioNTech (called BNT162b2) in people taking different treatments for their underlying AIIRD. 

The authors wanted to investigate people’s antibody response to the BNT162b2 vaccine over time. Specifically, they wanted to look at the level of protective antibodies directed against the spike protein of the COVID-19 virus in people with rheumatic diseases. They also wanted to see the impact of immunosuppressive treatments on the response to vaccination.

Overall, the study looked at 729 adults. These people had a variety of rheumatic diseases and were taking different immunosuppressive treatments. The study also included a control group of 122 adults who did not have rheumatic diseases and were not taking immunosuppressant treatments. 

Because some people dropped out of the study, only 186 patients and 45 controls were enrolled for the evaluation of the response to the booster dose. The main reasons for dropout included unwillingness to provide a blood test or being lost to follow-up. The rapid rollout of the third vaccine dose was also responsible for people deciding not to participate at this stage.

The study took place at three medical centres in Israel. Everyone received two doses of the BNT162b2 vaccine, given 3 weeks apart. The third (booster) vaccine dose was offered to all study participants, at least 6 months after the first vaccine dose, in line with the national guidelines. People with an AIIRD were told to continue all their regular anti-rheumatic medications during the vaccination period. The only exception was rituximab, which was postponed until after vaccination in certain cases. 

Blood tests to measure the antibody response to vaccination were taken at 2–6 weeks and 6 months after the second vaccine dose, and 2–6 weeks after the booster. A second measure of immune response to the booster – evaluation of the cellular T-cell response – was also evaluated in a small sample of people. 

COVID-19 infections that happen after vaccination are called a breakthrough infection. People in the study were asked if they had contracted COVID-19 following each vaccine dose. Positive cases were confirmed by PCR testing. Medical files were also reviewed for evidence of a COVID-19 infection.

The authors found that after receiving the initial two vaccine doses there was a similar decline in anti-spike antibody level in people with rheumatic disease and controls over the next 6 months. The antibody level was restored by the booster in all controls and the majority of people with AIIRD – with the exception of those treated with rituximab, in whom only one-third showed restoration of the antibody response.

There were some differences in how different anti-rheumatic drugs affected the vaccine response. Methotrexate, biologics, abatacept, and JAK inhibitors did not stop people from developing a spike antibody response after the booster vaccine. In contrast, treatment with rituximab was associated with a significantly impaired antibody response at all time points. 

It was found that some factors could predict whether somebody taking rituximab would have an adequate antibody response to the booster. This included having received fewer rituximab courses in the past, and having a longer interval between last course and the booster vaccine.

The cellular immune response was preserved before and after the third vaccine dose, and was similar in both groups of people. 

Over the course of the study, 14 people with a rheumatic disease (1.83%) had a breakthrough COVID-19 infection. This included 11 cases in people who had received two vaccine doses, and 3 cases after the booster dose. Two people with rheumatic diseases were hospitalised due to severe COVID-19. Among the controls, two people (1.43%) got COVID-19 after two vaccine doses.

The findings of this study shed light on the dynamics of the protective spike antibody response to a serial COVID-19 vaccination among both people with rheumatic diseases and controls. The two-dose BNTb262 regimen was associated with similar decline of the antibody response over 6 months in both groups. 

The observation that the booster dose restored the antibody level in all controls and the majority of people with rheumatic disease was the new finding. In addition, the impact of different treatments on the response to vaccination confirmed that there was a preserved antibody response with most anti-rheumatic drugs. 

One limitation was that there was a significant drop in the number of participants at the booster vaccine stage. 

Also, because the study took place before the emergence of the Omicron variant, the findings do not necessarily apply to this strain.

The study is ongoing, so the authors are collecting more data on the Omicron surge and further vaccine boosters.


If you have a rheumatic disease, the best protection against COVID-19 is getting vaccinated. The results of this study support the policy of giving people with rheumatic disease a booster dose. 

If you are taking rituximab, this study suggests that the time interval between your last treatment and vaccination can affect whether you develop an antibody response to the vaccine. This should be considered when planning when to have your vaccine doses. At this time, there does not appear to be a need to stop other anti-rheumatic drugs at the time of vaccination.  

Protect yourself from COVID-19 by following the advice of the government in your country. Where recommended, follow social distancing rules, and use protective masks. Wash your hands regularly, and avoid touching your face. Maintaining good ventilation may also help stop the virus spreading. 

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Date prepared: October 2022
Summary based on research article published on: 22 July 2022

From Furer V, et al. Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study. Ann Rheum Dis 2022;81(11):1594–1602. doi:10.1136/annrheumdis-2022-222550

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