Holding biologics for a vaccine dose gave no antibody gain and more flares

Design

Pragmatic multicentre randomised trial

Population

840 adults with inflammatory arthritis on biologic or JAK inhibitor therapy

Primary outcome

Fold rise in anti-spike IgG at 6 weeks

Effect

GMFR ratio 0.96 (95% CI 0.36-2.56); flare OR 2.27 (1.41-3.65)

The COVER trial randomised 840 adults with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis, on stable TNF inhibitors, IL-17 inhibitors, abatacept or JAK inhibitors, to continue or hold their drug for two weeks after a COVID-19 booster. Published in JAMA Internal Medicine on 5 October 2026.

Antibody rises were substantial in both groups and did not differ (ratio of fold rise, hold versus continue, 0.96, 95% CI 0.36 to 2.56). Holding more than doubled the odds of a flare (OR 2.27, 95% CI 1.41 to 3.65), most of all with JAK inhibitors; 21% versus 9% had a clinically important worsening on a flare questionnaire. Flares had settled by six weeks.

Many physicians still advise holding immunomodulators around vaccination. For these drug classes, the trial shows the cost without the benefit.

The result applies to COVID-19 boosters in previously vaccinated patients; it does not cover rituximab, methotrexate or other vaccines. Within that scope, continuing therapy is the better default.

• Continue TNF inhibitors, IL-17 inhibitors, abatacept and JAK inhibitors through COVID-19 booster doses
• Expect flares if JAK inhibitors are paused around vaccination
• Do not extrapolate to rituximab, where vaccine timing still matters
• Use the admission or clinic visit to bring vaccinations up to date without interrupting treatment

Why it matters

It removes a common, well-meant instruction that harms patients without helping the vaccine work.

Don't overread it

The antibody comparison had a wide confidence interval and measured antibodies, not protection against infection.

The statistics, in plain English

The antibody ratio's confidence interval (0.36 to 2.56) is wide, so a modest difference either way cannot be excluded. The flare result is firmer: the interval for the odds ratio stays well above 1.

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