Pausing Biologics or JAK Inhibitors for COVID-19 Boosters Raises Flare Risk, Not Antibodies

Temporarily holding biologic or Janus kinase (JAK) inhibitor therapy for 2 weeks after a supplemental COVID-19 vaccine dose did not improve antibody responses in patients with inflammatory arthritis but was associated with higher odds of disease flare, according to the COVID-19 Vaccine Response (COVER) randomized clinical trial published in JAMA Internal Medicine.

The multicenter pragmatic trial, conducted from November 2021 to May 2024, enrolled patients with rheumatoid arthritis (RA), psoriatic arthritis, and axial spondyloarthritis receiving care in the Excellence Network in Rheumatology to Innovate Care and High-Impact Research practice-based network. Participants had completed a primary mRNA COVID-19 vaccine series and were receiving stable immunomodulatory therapy with agents that included anti-tumor necrosis factor agents, anti-interleukin-17 agents, abatacept, and JAK inhibitors. They were randomized to continue or hold therapy for 2 weeks after their next supplemental dose.

The primary outcome was the change in IgG against the SARS-CoV-2 spike protein from baseline to 6 weeks, expressed as the geometric mean fold rise (GMFR). Among 840 randomized participants, antibody levels increased substantially in all groups. In the intention-to-treat analysis, the GMFR ratio for hold vs continue was 0.96 (95% CI, 0.36-2.56), indicating no significant difference. Results were consistent across drug subgroups and drug half-life categories.

Holding therapy was associated with higher odds of disease flare (odds ratio, 2.27; 95% CI, 1.41-3.65), an effect most pronounced among JAK inhibitor users. The Outcome Measures in Rheumatology RA Flare Questionnaire corroborated the signal, with a risk difference of 12.0% (95% CI, 5.9%-18.1%) for worsening of 10 points or more. Both arms fully recovered by 6-week follow-up.

The investigators described the flares as transient but clinically meaningful and concluded that routine interruption of these therapies at the time of COVID-19 vaccine dosing is "likely not warranted."

Source: Curtis JR, Mudano AS, Cutter G, et al. Temporary cessation of DMARD therapy and COVID-19 supplemental dose vaccine immunogenicity in patients with inflammatory arthritis: the COVER randomized clinical trial. JAMA Intern Med. Published online October 5, 2026. doi:10.1001/jamainternmed.2026.4894