No Benefit Seen in Holding RA/SpA Meds for COVID-19 Vaccine

WASHINGTON — There is no benefit to interrupting treatment with many of the available targeted synthetic or biologic disease-modifying antirheumatic drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) at the time of a repeat COVID-19 vaccine dose, new research found.
In the multicenter, randomized controlled COVID Vaccine Response (COVER) trial of 577 patients with RA or SpA taking either abatacept, Janus kinase (JAK) inhibitors, interleukin-17 (IL-17) inhibitors, or tumor necrosis factor (TNF) inhibitors, holding those drugs for 2 weeks at the time of COVID-19 vaccination supplemental doses didn’t improve antibody response to the vaccine but did lead to disease flares. Most participants had significant antibody responses to the vaccine, regardless of whether their medication had been held or continued, Jeffrey R. Curtis, MD, the Harbert-Ball Professor of Medicine, Epidemiology, and Computer Science at The University of Alabama at Birmingham, reported at the American College of Rheumatology (ACR) 2024 Annual Meeting.
Guidelines issued by ACR in 2023 recommended holding abatacept for the COVID vaccine but said that “the task force failed to reach consensus” on whether or not to temporarily interrupt the other medications following primary vaccination or supplemental/booster dosing.
Curtis, who was an author on those guidelines, told Medscape Medical News, “to date, we haven’t known whether it might be a good idea to hold certain drugs at the time patients receive their next dose of the COVID vaccine…That’s because without direct evidence, you have people trading opinions based on extrapolated data.” 
The inability to measure cell-mediated immunity and only humoral (ie, antibody-based) immunity is a limitation in COVER. “Nevertheless, based on what we know now, it isn’t advisable to hold any of the four drug classes that we studied at the time patients receive their next COVID vaccine dose. This finding is in contrast to data from a different trial showing that holding methotrexate for 2 weeks does appear to help in response to COVID-19 vaccination, as well as influenza vaccine,” Curtis said.
Asked to comment, session moderator Elena Myasoedova, MD, PhD, consultant rheumatologist and director of the Inflammatory Arthritis Clinic at the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News, “This has been an area of clinical uncertainty. It raises a lot of questions from patients and from physicians alike as to whether or not to hold the medication because the implications are flares, and that’s impactful for patients. Patients care about their RA status and how it is controlled, and if there is no difference, then there is no reason to change the medication regimen.”
To Hold or Not to Hold: COVER Shows It Makes Little Difference to Vaccine Response
In COVER, 128 patients were taking abatacept, 96 IL-17 inhibitors, 237 JAK inhibitors, and 116 TNF inhibitors. The study was conducted within 30 sites of the Excellence Network in Rheumatology, a rheumatology practice–based research network launched in 2021. Participants were identified and enrolled at clinic visits immediately prior to receiving their COVID-19 boosters (in routine settings).
All had previously received two or more doses of the mRNA vaccines made by Pfizer or Moderna. Blood was drawn, and they were randomized 1:1 to either continue or hold their disease medication for 2 weeks following the booster. Blood was collected again at 6 weeks post-vaccine.
Anti–receptor-binding domain (RBD) IgG antibody titers increased significantly in all drug categories across both study arms, with no differences between the hold and continue medication groups, even after adjustments for age, sex, body mass index, methotrexate use, steroid use, and time from booster to measurement. All groups also showed increases in geometric mean fold rise of more than 3%.
Subgroup analyses showed no major differences between antibody responses in the hold vs continue groups. The anti-RBD IgG response was lower for abatacept and JAK inhibitors than for the other two drugs, but there was still no significant benefit to holding them for 2 weeks post-vaccination.
Holding Drugs Leads to Disease Flares
On the flip side, there were significant differences between the two groups in their responses to the question, “Did you experience any flare or worsening of your autoimmune disease following your recent COVID-19 booster dose?” Overall, 27% of the hold group responded that they had compared with just 13% of the continue group (P < .05). This difference was greatest in the JAK inhibitor group (33% vs 9%; P < .05).
Among those reporting flares or worsening disease, both the severity and the duration of the flares were about the same. “Interestingly, the duration is beyond a week for the majority of patients. The reason that’s important is, any symptoms that are so-called flare might simply be reactogenicity symptoms, and that might be confused for flare or disease worsening, but you see that a majority of patients actually have those symptoms extending beyond the week. Most of them are worsening in arthritis, as you might expect,” Curtis said in his presentation.
Asked what they did about the flare, only a minority of patients reported contacting a healthcare provider. In all, 68% of the hold group and 78% of the continue group took no action. That’s good in the sense that most of the flares weren’t severe, but it has implications for research, Curtis pointed out.
“A lot of times in the vaccine literature, people do retrospective chart review by looking to see what the doctor said as to whether the patient had a flare. And what this would tell you is patients may be reporting a lot of flares that their doctor doesn’t know anything about. So if you really want to know whether people are having a flare, even a mild flare, you really have to collect prospective data.”
COVID Is Not the Last Pandemic
“These results are reassuring, although I think we need a bit more data on abatacept,” Myasoedova said, adding, “I was also interested in the outcomes, such as severe infections, that actually happened to these patients. What we see in the labs in their immune response is one thing, but then also important is what actually evolves in terms of the outcomes, especially with abatacept.”
Overall, she said, “I think it’s reassuring and definitely informs clinical practice going forward. But then probably we’ll learn more. What we’re hearing is COVID is not the last pandemic.”
The COVER trial receives support from AbbVie, BMS, Eli Lilly and Company, Novartis, and Pfizer. Curtis has received research grants and consulting fees from AbbVie, Amgen, BMS, GSK, Eli Lilly and Company, Novartis, Pfizer, Sanofi, and UCB. Myasoedova has no disclosures.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in The Washington Post, NPR’s Shots blog, and Diatribe. She is on X: @MiriamETucker.
 
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