WASHINGTON DC New research has found that at the time of repeat dosing of the COVID-19 vaccine, there is no benefit in stopping treatment with many of the synthetic disease-modifying antirheumatic drugs or targeted biologics available for arthritis rheumatoid (RA) or spondyloarthritis (SpA). In the multicenter, randomized, controlled COVID Vaccine Response (COVER) trial of 577 patients with rheumatoid arthritis or spondyloarthritis taking abatacept, Janus kinase (JAK) inhibitors, interleukin-17 (IL-17) inhibitors, or factor inhibitors of tumor necrosis (TNF), stopping treatment with these drugs for two weeks at the time of supplemental doses of the COVID-19 vaccine did not improve the antibody response to the vaccine, but it did cause outbreaks of the disease. Most participants had significant antibody responses to the vaccine, regardless of whether they had stopped or continued the medication, reported Dr. Jeffrey R. Curtis, Harbert-Ball Professor of Medicine, Epidemiology and Computer Science at the University of Alabama at Birmingham, in the Annual Congress of American College of Rheumatology (ACR) 2024.
The recommendations issued by the American College of Rheumatology in 2023 they suggested suspending the use of abatacept for the anti-SARS-CoV-2 vaccine, but said that “the working group was unable to reach a consensus” on whether or not the other drugs should be temporarily stopped after primary vaccination or the complementary/booster dose.[1]
Dr. Curtis, who was one of the authors of those recommendations, commented to Medscape Medical News: “To date, we haven’t known whether it might be a good idea to stop certain drugs at the time patients receive their next dose of the COVID-19 vaccine… That’s because, without direct evidence , there are people who exchange opinions based on extrapolated data.”
The inability to measure cell-mediated immunity and only humoral (i.e., antibody-based) immunity is a limitation in COVER. “However, based on what we know now, it is not advisable to stop any of the four classes of drugs we studied at the time patients receive their next dose of the COVID-19 vaccine. This finding contrasts with the data from a different trial showing that stopping methotrexate for two weeks appears to help the response to COVID-19 vaccination as well as the flu vaccine,” Dr. Curtis said.
When asked to comment, the session’s moderator, Dr. Elena Myasoedova, PhD, a consultant rheumatologist and director of the Inflammatory Arthritis Clinic at the Mayo Clinic in Rochester, United States, told Medscape Medical News: “This has been an area of clinical uncertainty. It raises a lot of questions for both patients and doctors about whether or not to stop medication, because the implications are flares and that has an impact on patients. Patients find that “It matters your rheumatoid arthritis status and how it is controlled, and if there is no difference, then there is no reason to change the treatment regimen.”
To suspend or not to suspend? COVER shows it makes little difference to vaccine response
In COVER, 128 patients were being treated with abatacept, 96 with interleukin-17 (IL-17) inhibitors, 237 with Janus kinase inhibitors, and 116 with tumor necrosis factor inhibitors. The study was conducted at 30 sites in the Excellence Network in Rheumatology, a rheumatology practice-based research network launched in 2021. Participants were identified and enrolled in clinical visits immediately before receiving their booster doses against COVID-19 (in routine settings).
All had previously received two or more doses of the mRNA vaccine manufactured by Pfizer o Modern. They had blood drawn and were randomly assigned 1:1 to continue or stop anti-disease medication for two weeks after the booster dose. Blood was drawn again six weeks after the vaccine.
Anti-receptor binding domain (RBD) immunoglobulin G (IgG) antibody titers increased significantly in all drug categories in both study groups, with no differences between medication discontinuation and continuation groups, even after adjustment for age. , sex, body mass index, methotrexate use, steroid use, and time from booster dose to measurement. All groups also showed an increase in the geometric mean of more than 3%.
Subgroup analyzes showed no significant differences between antibody responses in the discontinuation and continuation groups. The anti-RBD IgG response was lower for abatacept and Janus kinase inhibitors than for the other two drugs, but there was still no significant benefit from discontinuing them for two weeks after vaccination.
Discontinuation of medication causes disease flares
On the other hand, there were significant differences between the two groups in their responses to the question “Did you experience any flare-ups or worsening of your autoimmune disease after your recent COVID-19 booster dose?” Overall, 27% of the group who stopped the medication said yes, compared to only 13% of the group who continued (p p
Among those who reported flares or worsening of illness, both the severity and duration of flares were similar. “Interestingly, the duration is longer than a week for most patients. The reason this is important is that any symptom that is called a flare could simply be a symptom of reactogenicity and that could be confused with a flare or worsening of the disease , but you can see that most patients actually have those symptoms that extend beyond the week. Most of them get worse in arthritis, as you would expect,” Dr. Curtis detailed in his presentation.
When asked what they did about the outbreak, only a minority of patients reported contacting a healthcare provider. In total, 68% of the wait group and 78% of the continuation group took no action. That’s good in the sense that most outbreaks were not serious, but it has implications for research, Dr. Curtis said.
“A lot of times in the vaccine literature, people do a retrospective review of the records to see what the doctor said about whether the patient had a flare. What this would tell you is that patients may be reporting a lot of flares.” that their doctor doesn’t know anything about. So if you really want to know if people are having a flare, even a mild one, what you have to do is collect prospective data.”
COVID-19 is not the last pandemic
“These results are reassuring, although I think we need a little more data on abatacept,” Dr. Myasoedova said, adding: “I was also interested in the results, for example on serious infections, that actually happened to these patients. “What we see in the labs in your immune response is one thing, but what actually evolves in terms of outcomes is also important, especially with abatacept.”
Overall, he added, “I think it’s reassuring and definitely informs clinical practice going forward. But then we’ll probably learn more. What we’re hearing is that COVID-19 is not the last pandemic.”
The COVER trial is supported by AbbVie, BMS, Eli Lilly and Company, Novartis and Pfizer. Dr. Curtis has received research grants and consulting fees from AbbVie, Amgen, BMS, GSK, Eli Lilly and Company, Novartis, Pfizer, Sanofi, and UCB. Dr. Myasoedova has disclosed no relevant financial relationships.
This content was originally published in the English edition of Medscape.
