An illustration of a medical disposable syringe filled with the COVID-19 vaccine.
Credit: Andrii Shyp/iStock

Key Takeaways

  • Current ACR recommendations advise pausing methotrexate for one week after each dose of the mRNA vaccines (Pfizer or Moderna), provided your disease is well-controlled. 
  • Pausing methotrexate for two weeks after each shot dose resulted in sufficient antibody response in 80 percent of study participants.  
  • Stopping the drug was also linked to increased disease activity in 38 percent of participants. 
  • Deciding whether to pause methotrexate after your COVID shot needs to be a shared decision between you and your doctor. 

Most people with rheumatoid arthritis (RA) use methotrexate, sometimes in conjunction with another medication, to control their disease. The catch is that methotrexate reduces immune system activity, which can hinder your response to vaccines. 

Many rheumatologists have long advised RA patients to stop methotrexate for two weeks after getting a flu shot, a move that has been shown to improve protection from the flu vaccine without worsening RA disease activity. The COVID vaccines, however, are relatively new, so research regarding how to best use them if you have an autoimmune disease is still emerging.  

The American College of Rheumatology currently recommends that patients taking methotrexate pause the drug for one week after each dose of the mRNA vaccines (Pfizer or Moderna), provided their RA has been relatively well-controlled. Now a new study, published in the Annals of the Rheumatic Diseases, sheds some more light on the pros and cons of taking a break from this drug to support vaccine response.  

The new study focuses on RA patients in Brazil who received two doses of Sinovac’s CoronaVac vaccine. CoronaVac, which has been widely administered in many countries, is not an mRNA vaccine; it’s made using a more traditional approach that entails growing the virus in a lab and inactivating (killing) it.  

The researchers randomly assigned participants to one of two groups: 60 RA patients were advised to stop methotrexate two weeks after each dose of the vaccine, and another 69 were told to continue their regular methotrexate regimen.

As expected, those who paused methotrexate after each shot dose gained more protection — 80 percent achieved a sufficient antibody response from the COVID vaccine series — compared to a 55 percent response in those who did not stop methotrexate.  

Unfortunately, 38 percent of those who interrupted their methotrexate regimen also had increases in their RA disease activity (Clinical Disease Activity Index scores above 10) versus 20 percent of those who didn’t alter their methotrexate use. 

What does this all mean for patients? It really comes back to shared decision-making — meaning that each patient should have an in-depth discussion with their rheumatologist about whether pausing methotrexate is likely to lead to a significant or hard-to-control flare.   

Found This Study Interesting? Get Involved

If you are diagnosed with arthritis or another musculoskeletal condition, we encourage you to participate in future studies by joining CreakyJoints’ patient research registry, ArthritisPower. ArthritisPower is the first-ever patient-led, patient-centered research registry for joint, bone, and inflammatory skin conditions. Learn more and sign up here.

Araujo C, et al. “Two-Week Methotrexate Discontinuation in Patients with Rheumatoid Arthritis Vaccinated with Inactivated SARS-CoV-2 Vaccine: A Randomised Clinical Trial.” Annals of the Rheumatic Diseases. February 2022. doi: 

Curtis J, et al. “American College of Rheumatology Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 2.” Arthritis & Rheumatology. August 2021. doi: 

Precision Vaccinations. CoronaVac COVID-19 Vaccine (Sinovac). March 2022. 

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