Research Summary

Withholding Biologics or JAK Inhibitors After COVID Boosters Raises Arthritis Flare Risk Without Antibody Benefit

Edited by:
Brian McCurdy

Key Highlights

  • Antibody responses did not differ significantly between patients who held therapy and those who continued treatment.
  • Holding therapy increased the odds of disease flare (OR, 2.27; 95% CI, 1.41–3.65), most prominently among JAK inhibitor users.
  • A flare questionnaire corroborated transient worsening, with recovery in both groups by 6 weeks.
  • The investigators concluded that routine interruption of the studied therapies around supplemental COVID-19 vaccination is likely unwarranted.

Temporarily withholding selected biologic or Janus kinase (JAK) inhibitor therapies after supplemental COVID-19 vaccination did not significantly improve antibody responses but increased arthritis disease flares in a randomized clinical trial. The findings involved 840 patients with inflammatory arthritis.

The COVID-19 Vaccine Response (COVER) trial examined whether briefly interrupting immunomodulatory treatment could improve vaccine immunogenicity without worsening rheumatic disease activity. Investigators conducted the multicenter pragmatic trial from November 2021 through May 2024 within the ENRICH practice-based rheumatology network.

Participants had rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis, had completed a primary messenger RNA COVID-19 vaccine series, and were receiving stable therapy with anti–tumor necrosis factor agents, anti–interleukin-17 agents, abatacept, or a JAK inhibitor. They were randomized to continue treatment or hold it for 2 weeks following their next supplemental vaccine dose.

The primary outcome was the change in SARS-CoV-2 spike immunoglobulin G levels from baseline to 6 weeks, expressed as geometric mean fold rise (GMFR). The primary intention-to-treat analysis used multiple imputation for missing outcomes; investigators also conducted a per-protocol sensitivity analysis. Secondary outcomes included disease flares and vaccine-related adverse events.

Study Findings

Antibody levels increased substantially from baseline across all groups. The GMFR ratio for holding versus continuing therapy was 0.96 (95% CI, 0.36–2.56), showing no statistically significant difference in humoral immunogenicity. Findings were consistent across drug subgroups and medication half-life categories.

Holding treatment significantly increased disease flare risk (OR, 2.27; 95% CI, 1.41–3.65), with the strongest signal among JAK inhibitor users. On the Outcome Measures in Rheumatology RA Flare Questionnaire, 54 of 256 participants who held therapy (21.1%) experienced worsening of at least 10 points, compared with 23 of 253 who continued therapy (9.1%). The risk difference was 12 percentage points (95% CI, 5.9–18.1). Both groups showed full recovery by the 6-week follow-up.

Clinical Implications

According to the investigators, these results do not support routinely interrupting the studied biologic or JAK inhibitor therapies to improve supplemental COVID-19 vaccine immunogenicity. They characterized the associated flares as transient but clinically meaningful, despite recovery by 6 weeks.

Expert Commentary

“Routine interruption of these therapies at the time of COVID-19 dose administration is likely not warranted,” the researchers concluded.

Reference

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