COVID-19 Vaccines Produce Immune Responses in Patients With Chronic Inflammatory Diseases

But UCSF-Washington University Study Finds Some Treatments Inhibit Effects Much More Than Others

By Suzanne Leigh

a hand reaches for a COVID-19 vaccine sitting in a tray

Photo by Barbara Ries

Most patients on immunosuppressive drugs for chronic inflammatory conditions, like rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease, can still produce antibodies after receiving the mRNA COVID-19 vaccines, researchers at UC San Francisco and Washington University have concluded.

The study, published online on Aug. 30, 2021, in Annals of Internal Medicine, found that 89 percent of patients with inflammatory conditions produced detectable antibodies in response to the vaccine. These responses differed by drug, however, and some participants produced low antibody levels.

“Since it is unknown what the cutoff is for antibody protection, it is hard to predict the extent to which the reduced antibody titers alter protection of patients with chronic inflammatory disease,” said co-author Mary Nakamura, MD, of the UCSF Rheumatoid Arthritis Clinic, who led the UCSF research team.

“Additionally, it is difficult to distinguish between the role of the underlying disease and the role of medications in contributing to the diminished capacity of the vaccine to prompt an immune response.”

The study included 186 participants at UCSF, Zuckerberg San Francisco General Hospital and Washington University School of Medicine, in St. Louis, Mo., 133 of whom had a chronic inflammatory condition, and 53 of whom did not.

The most common conditions were inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis (32 percent), rheumatoid arthritis (29 percent), lupus (11 percent) and multiple sclerosis (7 percent). These conditions are treated with immunosuppressants that block inflammation but also blunt the immune response to some vaccines.

Participants provided blood samples before receiving each dose of the Pfizer or Moderna vaccine and one to two weeks after receiving the second vaccination. Most patients remained on their medications since the study was done early in the vaccine roll out.

The study suggests that the type of treatment influences the degree of seroconversion, the process in which antibodies in the blood are present at any level above detection following infection or immunization. Notably, only 11 out of 17 patients on the corticosteroid prednisone had seroconverted, and six out of 10 patients on B-cell depletion therapy, which destroys autoimmune-producing B cells, had seroconverted.

The researchers found that other immunosuppressives including antimetabolites, such as methotrexate, taken by 29 of the patients, did not generate much weaker antibody responses than those not taking the drugs. The same was true for those patients on TNF inhibitors or JAK inhibitors.

COVID-19 Vaccine ‘Clearly a Benefit’ Despite Varied Antibody Responses

Because patients on immunosuppressives may be at increased risk for severe disease, as well as breakthrough infections, a third dose may be advisable.

Earlier this month, the American College of Rheumatology recommended a third dose of the mRNA vaccine in those receiving immunosuppressive drugs. That recommendation follows the Centers for Disease Control and Prevention’s communication that people with compromised immune systems “may benefit from an additional dose to make sure they have enough protection.”

Some patients are concerned that vaccination might cause the disease to flare, but that has not been observed, said co-senior author Alfred Kim, MD, PhD, of Washington University School of Medicine.

“Others don’t see the point of vaccination because they think the drugs they’re taking to treat their condition will prevent them from producing an immune response to the vaccine,” he said. “What we found here is that the vast majority of patients are able to mount antibody responses following COVID-19 vaccination. There’s clearly a benefit for this population.”

Authors: Co-senior author is Ali Ellebedy, PhD, of Washington University School of Medicine. First authors are Parakkal Deepak, MBBS, MS; Wooseob Kim, PhD, and Michael Paley, MD, PhD, all of Washington University School of Medicine. Other UCSF authors are Monica Yang, MD, Alexander Carvidi, Emanual Demissie, Diana Paez, Niti Pawar, Jonathan Graf, MD, Kimberly E. Taylor, PhD, MPH, Patricia Katz, PhD, Mehrdad Matloubian, MD, PhD, and Lianne Gensler, MD.

Funding: For information on grant support please refer to the paper. Information on disclosures is available here.