Pausing biologics or JAK inhibitors for two weeks failed to improve vaccine antibody responses but more than doubled the odds of disease flare in a randomised trial.
Stopping biologic or JAK inhibitor therapy for two weeks after a covid booster offers no significant immunological benefit and more than doubles the odds of an inflammatory arthritis flare, new research has found.
The findings, published in JAMA Internal Medicine, challenge the practice of temporarily withholding targeted immunomodulatory treatments to improve vaccine responses in patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.
The US multicentre COVER trial randomised 840 patients to either continue their prescribed treatment or interrupt therapy for two weeks following a supplemental covid vaccine dose.
Researchers found no significant difference in antibody responses between the groups, despite substantial increases in SARS-CoV-2 spike protein antibodies following vaccination.
However, patients who interrupted treatment had more than twice the odds of experiencing a disease flare or worsening symptoms compared with those who continued therapy (OR 2.27; 95% CI 1.41-3.65), the researchers said.
“In this randomized pragmatic clinical trial, holding biologic or JAKi therapy did not improve anti-RBD IgG responses, while disease flares were substantially more frequent in the hold arm, particularly among JAKi users,” the researchers wrote.
“These findings aligned with prior studies showing that immunomodulatory therapy effects on vaccine response and flare risk vary by drug class.”
Patients taking JAK inhibitors had more than three times the odds of flare when treatment was withheld (OR 3.65; 95% CI 1.69-7.87).
The pragmatic, open-label trial recruited patients from 29 rheumatology practices between November 2021 and May 2024. Participants had established rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis and were receiving stable treatment with TNF inhibitors, IL-17 inhibitors, abatacept, or JAK inhibitors.
All had previously completed a primary mRNA COVID-19 vaccination series.
Patients were randomly assigned to continue treatment as usual or temporarily withhold their medication for two weeks after their next COVID-19 booster.
The primary outcome was the change in anti-receptor-binding domain IgG antibody concentrations between baseline and six weeks after vaccination.
Antibody levels increased substantially in both groups, with an adjusted geometric mean fold rise of 4.69 among patients who withheld treatment and 4.86 among those who continued therapy. The ratio between groups was 0.96 (95% CI 0.36-2.56), indicating no statistically significant benefit from interrupting treatment.
The results were consistent across drug classes and when medications were grouped according to their half-lives.
Although abatacept and JAK inhibitor use were associated with weaker antibody responses compared with IL-17 inhibitors, temporarily stopping these treatments did not improve immunogenicity.
Concomitant methotrexate use was also associated with reduced antibody responses, although the trial did not require patients to interrupt conventional synthetic DMARDs.
The researchers said the findings demonstrated that a drug’s effect on vaccine immunogenicity did not necessarily mean a brief treatment interruption could reverse that effect.
Importantly, the increased disease activity associated with treatment interruption appeared to be transient.
Among 509 participants who completed an interim assessment using the OMERACT Rheumatoid Arthritis Flare Questionnaire, 21.1% of patients who withheld therapy experienced clinically meaningful worsening, compared with 9.1% of those who continued treatment. This represented an absolute risk difference of 12 percentage points (95% CI 5.9-18.1).
Related
The interim assessment was conducted a median of 10 days after vaccination, suggesting that the increased disease activity was concentrated in the first one to two weeks.
By the six-week follow-up, both groups had returned to comparable levels of disease activity, with 11.2% in each group meeting the threshold for clinically meaningful worsening.
Physician-assessed Clinical Disease Activity Index scores also showed no meaningful difference between groups at six weeks, the researchers said.
Patients who interrupted treatment reported more general symptoms following vaccination, including fatigue, muscle aches, and joint pain.
New or worsening fatigue was reported by 30% of patients in the interruption group compared with 19% of those continuing therapy.
The researchers acknowledged several limitations, including missing outcome data for 31% of participants, the open-label design, and the possibility that a two-week interruption was insufficient to substantially reduce circulating concentrations of longer-acting biologics.
The study also assessed antibody responses rather than cellular immunity or clinical protection against covid, meaning the findings could not establish whether interrupting treatment affected subsequent infection risk or disease severity.
However, the researchers said the combination of increased flare risk and no demonstrable antibody benefit argued against routinely withholding these treatments around covid vaccination.
“Given the increased flare risk and absence of humoral immunogenicity benefit, these findings do not support routine temporary interruption for Covid-19 vaccine optimisation,” they concluded.
“Whether such interruption affects clinical outcomes, including covid-19 infection risk or severity, was beyond the scope of this trial and remains an important area for future research.”
