Large International Study Says Flares Rare After COVID Vaccination

Dr. Curtis

The ACR guidelines and guidance are intended to be adaptable, living documents that get updated as evidence evolves, notes Jeffrey Curtis, MD, MS, MPH, Marguerite Jones Harbert-Gene Ball Endowed professor of medicine in the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham.² Therefore, the guidance on whether to hold or delay immunosuppressive medications in relation to timing a COVID-19 vaccine can change in the face of new evidence, and more recent guidance by the Centers for Disease Control & Prevention may supersede earlier guidance, Dr. Curtis said in an email interview.

An earlier study by Dr. Machado and other researchers indicated COVID-19 vaccines were well tolerated by most patients with IRMD and that disease flares were uncommon, occurring in 4.4% of patients with 1.5% who required changes to medication. Other smaller studies have looked at flares reported by patients and found a higher flare rate following vaccination, but often did not distinguish IRMD flares from short-term vaccine reactogenicity.

The New Study

In this larger, international study, Dr. Machado and fellow researchers gathered data on demographics, primary IRMD diagnosis and key medications, as well as vaccine type, date given and number of doses. Disease activity was assessed at first dose under the four categories of remission, low, moderate or high disease activity. It was assessed again after vaccination for development of an IRMD flare and for any medication changes that were added or increased in response to a flare.

Researchers reviewed physician-reported flares using the EULAR coronavirus vaccine (COVAX) registry, which includes data from several, mostly European, countries. Data were recorded from February 2021 to October 2022 by rheumatologists or their clinical team members into a secure web application or transferred from a national registry.

The patient population included only people who had received one or two COVID-19 vaccines and had a preexisting IRMD diagnosis. Patients were excluded from the study if they received a combination of vaccines from different brands.

Medications documented at the time a COVID-19 vaccine was given included disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate and leflunomide; biologic DMARDs, such as rituximab and belimumab; tumor necrosis factor (TNF) inhibitors; Janus kinase (JAK) inhibitors; immunosuppressants; and other drugs, including intravenous immunoglobulin and antifibrotics.

Flares were defined by signs and symptoms local physicians interpreted as suggesting a post-vaccination IRMD flare. Information was collected about the type and severity of flares, changes in anti-rheumatic medication and time between vaccination and the flare.