People on immune-suppressing medications were excluded from the clinical trials. It has been unclear whether the vaccine behaves the same in someone on these drugs as it does in the healthy people studied in the trials. Now, answers are starting to emerge, and it appears those concerns may have been warranted. A study published May 25 in the Annals of the Rheumatic Diseases found that up to one-third of people taking methotrexate failed to achieve an adequate immune response to the shot. RELATED: 8 Things People With RA Must Know About COVID-19 Vaccinations “Our study is important because it is one of the first that shows that a portion of patients on methotrexate are making a weaker antibody response,” says study coauthor Rebecca Haberman, MD, a clinical instructor in medicine at NYU Grossman School of Medicine and a rheumatologist at NYU Langone Health in New York City.
This Study Examined Pfizer Vaccine Only
The study was small, involving just 82 people in New York City or Erlangen, Germany, with RA, psoriatic arthritis (PsA), or other immune-mediated inflammatory diseases who were taking methotrexate, TNF inhibitors, or other biologic medications. This group was compared with another 200 who were healthy and on no medications. RELATED: Vaccinated Against COVID-19 But Still Anxious? You’re Not Alone All of the people had gotten the Pfizer-BioNTech COVID-19 vaccine after it was authorized. More than 90 percent of the healthy people or those on drugs other than methotrexate produced adequate antibody levels in response to the vaccine. But in those taking methotrexate, only 62 percent did. In addition, certain T cells, another part of the body’s immune defense, were not as robust in the methotrexate group compared with the others. RELATED: Coronavirus Alert: The Latest News, Data, and Expert Insights on the COVID-19 Pandemic It isn’t yet clear whether this means the virus can sufficiently penetrate the vaccine’s defenses. “We don’t yet know what level of antibody response ultimately means protection — in other words, even if methotrexate lowers the number of antibodies in certain individuals, that does not necessarily mean that the vaccination is not protective in them,” Dr. Haberman says.
A Similar Reduced Immune Response Can Occur With Flu Vaccine
One of the reasons doctors and patients have been concerned about methotrexate is because the drug has previously been shown to reduce immune response to the influenza vaccine in some patients. “We don’t know the mechanism by which methotrexate lowers antibody response to the flu vaccine,” Haberman says. The reason for the drop in COVID-19 response is similarly unclear. RELATED: The Facts on Methotrexate for Rheumatoid Arthritis Treatment But it does point out that not everyone is the same when it comes to armoring up against COVID-19. “It is imperative to know where the gaps exist so that we can address them and ensure that all of our patients are properly protected,” she says.
More Research Is Needed, New Data Has Limitations
The study had a very small sample size and tested only one of the three COVID-19 vaccines authorized in the United States. It was also observational, rather than a randomized controlled clinical trial where researchers are better able to establish causality. Also, the people in the study taking methotrexate were older than the comparison group (their average age was 63, versus 49 for the others). And because they weren’t tested for antibodies, some of the people in either group might have had an asymptomatic COVID-19 infection previously, which could perhaps influence vaccine response. RELATED: 10 Foods to Help Beat RA Inflammation The researchers consider this to be only a first step in assessing the best vaccine approach for people with RA. “Ultimately, it will be important to look at each medication (or medication class) separately. We also need to know what happens at later time points. Right now, for example, we are analyzing how our patients are responding at three months and will continue to follow them,” Haberman says.
What This New Information Means for People With Inflammatory Arthritis
Already, recommendations by the American College of Rheumatology call for holding the dosing of methotrexate for one week after each vaccine dose for those with well-controlled disease. People with RA who are on this medication should work with their physician to discuss their specific drug regimen.
People With RA Should Still Get Vaccinated Against COVID-19
But this should not stop anyone from getting the vaccine, experts say. “Some protection is better than not getting vaccinated at all,” says Daniel Hernandez, MD, director of medical affairs and Hispanic outreach at CreakyJoints, a digital community for arthritis education and advocacy, and the Global Healthy Living Foundation. Chronic disease patients face a potentially elevated risk for severe outcomes from COVID-19 compared with the general population, including for hospitalization and death, he notes. RELATED: RA Drug Methotrexate Tied to Higher Risk of Skin Cancer, Other Risks That’s why CreakyJoints recommends that people who are immunocompromised speak with their doctor and also continue to follow safety precautions against COVID-19, including social distancing and potentially wearing masks, even after mandates are lifted. Haberman points out that two-thirds of the people on methotrexate did produce a robust vaccine response. And those on other medications, including TNF inhibitors, do not seem to have the same issue with the Pfizer vaccine. “People should speak to their doctors about getting the vaccination and discuss their specific rheumatoid arthritis medications,” she advises.
Researchers Seek Additional Answers About Strategies, Ways to Enhance Response
More information is needed to better understand why this happens and what it means for people with RA who want to best protect themselves from COVID-19. The Global Rheumatology Alliance, for instance, a worldwide effort to track COVID-19 in people with rheumatological diseases, has set up a vaccine survey for adults around the world to report their experiences. Scientists will use these results to help inform patient treatment. And Haberman’s team is examining whether alternative vaccination strategies might better boost response in those on methotrexate who did not react as robustly. They also hope further studies can determine whether modifying the dosages of methotrexate or perhaps temporarily discontinuing the drug might possibly enhance vaccine response.
