People with inflammatory arthritis who paused their medication before getting a COVID-19 vaccination gained no extra immune protection from the shot. That is the finding from a randomized trial involving 840 patients, published in JAMA Internal Medicine. The only thing the drug holiday accomplished was a sharp increase in arthritis flares.
The study, called COVER, was designed to settle a debate that erupted when COVID vaccines first rolled out. Some physicians suggested that patients on immunosuppressive drugs should briefly stop taking them to allow the immune system to respond more robustly to vaccination. The new data argues against that approach.
Key facts
- 840 arthritis patients randomized to hold targeted DMARDs for 2 weeks or continue as usual around vaccination
- Antibody increases were nearly identical between groups, with a geometric mean fold rise ratio of 0.96
- Patients who held their medication more than doubled their odds of a disease flare (OR 2.27)
- Among patients tracked with a standard arthritis questionnaire, 21.1% in the hold group experienced meaningful worsening versus 9.1% who continued treatment
The Clinical Dilemma
When COVID vaccines launched in early 2021, immunosuppressed patients were a priority group. Their risk of severe COVID was high, and getting the best possible vaccine response seemed logical. Some clinicians floated the idea of pausing drugs that suppress antibody production, at least temporarily.
Targeted DMARDs, or disease-modifying antirheumatic drugs, work by taming parts of the immune system that drive arthritis and similar conditions. Some of these agents suppress antibody production broadly. The concern was that stopping them would allow the immune system to generate a stronger response to the vaccine.
The COVER trial tested this directly. Researchers at the University of Alabama at Birmingham enrolled patients with rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis. Half paused their medication for two weeks around vaccination. The other half continued on schedule. Neither patients nor investigators were blinded, but the assignment was random.
What the Numbers Show
Six weeks after vaccination, antibody levels had risen by a factor of roughly 4.7 in the hold group and 4.9 in the continuation group. The difference was negligible and well within the range of chance. No benefit emerged regardless of which type of DMARD patients were taking, whether TNF inhibitors, JAK inhibitors, interleukin-17 blockers, or abatacept.
The flares told a different story. Using a validated arthritis questionnaire, researchers defined clinically meaningful worsening as a 10-point change. That threshold was hit by 21.1% of patients who paused treatment, compared with 9.1% of those who stayed on their drugs. Most flares occurred in the first two weeks and resolved before the six-week follow-up, but the disruption was real and measurable.
The authors concluded that stopping these drugs temporarily offered no immune benefit while substantially raising the risk of arthritis flares, and therefore routine drug holidays around vaccination are not supported by the evidence.
Why This Matters for Patients
For patients, this simplifies a decision that once required weighing uncertain tradeoffs. Skipping medication carried a real cost in pain and disease activity, with no documented gain in vaccine protection.
Say you are a 48-year-old with psoriatic arthritis on a JAK inhibitor. Your rheumatologist mentions holding the drug around your next COVID booster. Based on this trial, you now have solid grounds to say no. The evidence shows you would gain nothing immunologically while inviting a flare that could set back your joint health by weeks.
The researchers also noted that patients with the weakest immune responses, including those on methotrexate, JAK inhibitors, or abatacept, might benefit from timing vaccination before starting biologic therapy when feasible.
What to watch next
Future studies may explore whether other drug classes behave differently, or whether different pause durations might yield different results. For now, the evidence strongly favors staying on arthritis medication when COVID vaccination is scheduled.
Key takeaways
- Temporarily stopping targeted DMARDs around COVID vaccination produces no measurable improvement in antibody response
- Patients who held their medication more than doubled their odds of experiencing an arthritis flare
- Flares from holding treatment were real but typically resolved within a few weeks
- Patients on certain drug classes, including methotrexate and JAK inhibitors, showed weaker vaccine responses overall, regardless of whether they paused treatment
- The practical advice is straightforward: stay on your arthritis medication when you book a COVID shot
Frequently asked questions
Does this study apply to all arthritis patients?
The trial enrolled patients with rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis who were on targeted DMARDs. Results may not apply to patients on conventional DMARDs like methotrexate alone.
Were any drug types associated with weaker vaccine responses?
Yes. Patients taking methotrexate, JAK inhibitors, or abatacept had muted antibody responses compared with other DMARD classes, regardless of whether they held the medication.
How long did the arthritis flares last?
Most flares occurred in the first two weeks after vaccination and resolved before the six-week follow-up endpoint. The researchers described the flares as real but self-limited.
Should patients still get COVID vaccinated while on arthritis drugs?
Yes. The trial found no benefit to stopping medication, and vaccination remains important for protecting immunosuppressed patients from severe COVID-19 outcomes.
What should patients discuss with their rheumatologist?
Patients already on targeted DMARDs should continue their regimen as scheduled around vaccination. Those planning to start biologic therapy might ask whether timing the first dose after vaccination could improve immune response.
Inspired by reporting from: medpagetoday.com