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: Ratio hold/continue 0.96 (95% CI 0.36-2.56); flare OR 2.27 (1.41-3.65)

COVER was a pragmatic randomised trial in a US rheumatology practice network. It enrolled 840 patients with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis on stable anti-TNF, anti-IL-17, abatacept or JAK inhibitor therapy, randomised to continue or hold the drug for two weeks after a COVID-19 booster.

Antibody rise at six weeks did not differ (ratio of fold-rise 0.96, 95% CI 0.36 to 2.56). Holding therapy more than doubled the odds of a flare (OR 2.27, 95% CI 1.41 to 3.65), most clearly with JAK inhibitors: 21% vs 9% had a meaningful worsening on a flare questionnaire. Flares had settled by six weeks.

This is about a COVID-19 booster on these specific drugs; it does not directly address methotrexate or other vaccines. But it removes the rationale for a common, well-meant instruction to stop a biologic around vaccination.

Do not routinely hold anti-TNF, anti-IL-17, abatacept or JAK inhibitors around a COVID-19 booster.
If a patient has been told to hold, expect a higher chance of a temporary flare, especially on a JAK inhibitor.
The trial did not test methotrexate or rituximab; follow specialist advice for those.
Ask about recent flares when a patient on a biologic presents after vaccination.

Why it matters

A precaution many physicians advise turns out to cost flares and buy no extra protection.

The statistics, in plain English

The antibody ratio's confidence interval (0.36 to 2.56) is wide, so a modest difference cannot be excluded, but there is no sign of benefit. The flare odds ratio's interval (1.41 to 3.65) stays well above 1, so the harm of holding is more certain than any benefit.