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If you have an inflammatory disease, such as rheumatoid arthritis, psoriasis, Crohn’s disease, or lupus, and take immunosuppressant medication to treat it, you’ve likely had a lot of questions about the COVID-19 vaccine. One concern that CreakyJoints and the Global Healthy Living Foundation has been hearing about a lot: vaccine effectiveness.

It’s been widely assumed that people taking medication that affects immune system function would have a dampened response to the COVID-19 vaccine, but until recently, there has been no hard data to show this.

However, that is starting to change, as studies are emerging on inflammatory disease patients who’ve received the COVID-19 vaccine. A small study (26 people) in the Annals of Rheumatic Diseases recently concluded that people were able to produce a sufficient amount of antibodies with relatively minimal side effects. Antibodies are parts of the immune system that recognize germs and foreign invaders.

Now there is preliminary data from a larger patient population (133 people), shared in a preprint study from researchers at Washington University in St. Louis and the University of California, San Francisco. Preprint means the research has not yet been published in a peer-reviewed journal.

CreakyJoints first wrote about the study and what it hoped to discover back when it launched in December 2020.

The main finding: “Most patients can mount an antibody response [to the vaccine] even on medication,” says study author Alfred Kim, MD, Assistant Professor of Medicine, Pathology, and Immunology at Washington University. “The response may not be as high as those who do not take immunosuppressives, but the drop is not very much, and most are still in the range of the immunocompetent [healthy] controls that we have measured. So for the vast majority of autoimmune patients, they can rest easier knowing they will mount a response.”

Researchers did find, however, that certain medications were associated with much lower responses to the vaccine.

This article will share what the study found and try to put the findings in context, but it’s important to remember a few key things first:

1. Even if the COVID-19 vaccine is some degree less effective those on immunosuppressant medication, it is still very important to get the vaccine. It can still provide lifesaving protection and keep you from getting very sick, or even sick at all.

2. Researchers and doctors don’t know how reduced levels of antibodies exactly translate to protection from COVID-19. Just because a medication is associated with a decreased antibody response doesn’t mean that the vaccine is not protective. It will take more time and research to learn more about how antibody levels, as well as other parts of the immune system, correlate with whether or not people get infected or sick with COVID-19.

3. A goal of research like this is to help doctors figure out how to better protect people with inflammatory diseases on immunosuppressant medication when they get the COVID-19 vaccine. These findings may help experts figure out, for example, who may need booster shots to improve vaccine effectiveness.

The Study Details

The study included 133 adults with chronic inflammatory diseases (CIDs) and 53 immunocompetent controls (people with healthy immune system function who do not take immunosuppressant medication).

Study recruitment began shortly after the Pfizer and Moderna COVID-19 vaccines were authorized in the U.S. — when the vaccine was mainly available to health care workers. Participants were limited to faculty, employees, staff, and patients of the Washington University School of Medicine and BJC Healthcare system and the University of California, San Francisco, UCSF Health, and Zuckerberg San Francisco General Hospital. Participants were recruited between December 10, 2020 and March 20, 2021.

The majority were female (74 percent) and white (88 percent), with an average age of 45.

The most common diagnoses included:

  • Inflammatory bowel disease (Crohn’s disease and ulcerative colitis): 30%
  • Rheumatoid arthritis: 27%
  • Spondyloarthritis (such as axial spondyloarthritis and psoriatic arthritis): 15%
  • Lupus: 11%
  • Multiple sclerosis: 7%

The most common immunosuppressive medications were anti-TNF biologics (29 percent) and methotrexate (22 percent). Anti-TNF biologics include such medications as Cimzia, Enbrel, Humira, Remicade, and Simoni/Simponi Aria.

Researchers collected blood from participants before their first vaccine dose and one to two weeks after their second vaccine dose. They measured levels of antibodies to the spike protein as well as levels of neutralizing antibodies, which help determine the ability of your antibodies to actually prevent infection.

What the Study Found

Across all participants as a whole, researchers found that there was a three-fold reduction in antibodies and neutralizing antibodies compared to healthy controls. While that may sound like a lot, the researchers say this means that “most [chronic inflammatory disease] patients developed robust anti-SARS- CoV-2 antibody responses after immunization.”

For context, “this actually isn’t that bad,” Dr. Kim shared on Twitter, “given that in controls a 20-fold difference in [antibody] titers was observed.”

Researchers did notice that certain medications were more problematic than others.

Glucocorticoids (steroids)

Glucocorticoid use resulted in a 10-fold reduction in antibodies, the researchers reported. It’s long been known that steroids can reduce immune system function, which is one of many reasons doctors want patients to use steroids sparingly — to take the lowest dose for the shortest time possible. Interestingly, in this study even people on low doses of steroids had reduced antibodies.

Current COVID-19 vaccine guidelines from the American College of Rheumatology and the National Psoriasis Foundation do not recommend tapering steroids before getting the vaccine.

But the researchers noted that “as most prednisone users were on other immunosuppressants in this study, efforts to taper prednisone as safely as possible while initiating additional therapies may be needed to permit optimal antibody responses from mRNA-based vaccines.”

In other words, it may be a good idea to ask your doctor if you can safely taper steroids, especially if you can get your disease under control with a different medication.

B-cell depleting therapies (such as rituximab)

Medications such as rituximab work by depleting B cells, which are an important part of how your immune system responds to vaccines. Doctors and researchers have been concerned that rituximab could cause a significantly diminished response to the vaccine.

The study found a 36-fold reduction in antibodies among people on these medications compared to healthy controls. This medication type had the biggest impact on antibody levels in the study.

While this isn’t necessarily surprising, it can be understandably alarming for people who take this therapy. Current guidance from the American College of Rheumatology suggests that people on rituximab get the COVID-19 vaccine a month before they are due for their next dose. Rituximab is typically given once every six months for a condition like rheumatoid arthritis, so getting the vaccine right just before your next dose — when your levels of B cells would be highest — may help increase vaccine effectiveness.

Dr. Kim noted that timing B-cell depleting therapy around the vaccine may be necessary to optimize responses.

Methotrexate and JAK inhibitors

Compared to healthy controls, people on methotrexate had on average a two- to-three-fold reduction in antibodies and neutralization, which the researchers called a modest impairment.

People taking JAK inhibitor medications (which include Xeljanz, Olumiant, and Rinvoq) also had a modest reduction in antibody levels — a 4.5-fold decrease compared to healthy controls.

Some organizations, such as the American College of Rheumatology, have recommended that people temporarily stop taking methotrexate or JAK inhibitors for a week after getting the vaccine to help improve its effectiveness.

Based on this data, the researchers say that people who did not stop these therapies after getting the vaccine can be reassured that the impact on antibody levels is modest.

Other medications

Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody levels and neutralization, the researchers said. IL-12/23 or IL-23 inhibitors include such therapies as Stelara, Tremfya, and Skyrizi; integrin inhibitors include Entyvio.

The other good news was that combining therapies, such as taking methotrexate along with a TNF inhibitor, did not have an additional reduction on antibody levels.

What This Research Means for You

The main takeaway for patients on immunosuppressive therapy is that this research, along with other preliminary studies, suggests that most chronic inflammatory disease patients mount only a moderately decreased antibody response to the COVID-19 vaccine compared to healthy controls.

While people on glucocorticoids and B-cell depleting therapy like rituximab had lower antibody responses than everyone else, one knows exactly what this means yet.

“This may translate into reduced protection, but to what extent remains unclear,” according to Dr. Kim, adding that “our data will generate more certain guidelines in the future regarding what should be done for these people.” He noted that he and other researchers are discussing a trial where an additional booster of vaccine is given to these patients, but this is still in early stages of discussion.

It’s also important to remember that no one knows how to interpret the connection between antibody levels and protection from COVID-19. You could have reduced antibody levels, but still be protected from the SARS-CoV-2 virus, in part because there are other aspects of the immune system that help fight disease.

As the researchers noted, “these data do not directly evaluate protection from SARS-CoV-2 infection nor prevention of hospitalization.”

The study also had some important limitations worth noting, including small sample sizes for several types of medications, preventing analysis. Additionally, the study could not evaluate differences between the two mRNA vaccines (those from Pfizer and Moderna) and it did not include data from people who received another type of COVID-19 vaccine (that from Johnson & Johnson). The study had limited racial and ethnic diversity; the researchers say that they have continued recruitment to address this.

Future reports from this project will look at other aspects of immune system function in response to the COVID-19 vaccine, how the vaccine works in variants of concern, more information on specific diseases and therapies, vaccine side effects, and impact on disease activity.

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COVID-19 Task Force Guidance Statements. National Psoriasis Foundation. April 1, 2021. https://www.psoriasis.org/covid-19-task-force-guidance-statements.

COVID-19 Vaccine Clinical Guidance Summary for Patients with Rheumatic and Musculoskeletal Diseases. American College of Rheumatology. February 8, 2021. https://www.rheumatology.org/Portals/0/Files/COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary.pdf.

Deepak P, et al. Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2. MedRxIV. April 7, 2021. doi: https://doi.org/10.1101/2021.04.05.21254656.

Geisen UM, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Annals of the Rheumatic Diseases. March 24, 2021. doi: https://doi.org/10.1136/annrheumdis-2021-220272.

Interview with Alfred Kim, MD, PhD. Assistant Professor of Medicine, Pathology, and Immunology at Washington University in St. Louis, Missouri

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