Published: 13 December 2023
Over 1 million people with weakened immune systems can improve their protection against COVID-19 by pausing their medication for 2 weeks after their booster jab, research finds.
The Vaccine Response On Off Methotrexate (VROOM) trial has already changed UK and international guidelines. Now its longer term results show the full extent of benefits to these patients.
NIHR and the Medical Research Council (MRC) funded the VROOM trial. Researchers at the University of Nottingham led the study.
Methotrexate is a commonly used immune-suppressing drug. It is taken by 1.3 million UK people. These include patients with inflammatory conditions such as rheumatoid arthritis and psoriasis. Many were among the 2.2 million vulnerable people advised to shield during the pandemic.
Methotrexate is effective at controlling inflammatory conditions. But it reduces the body’s ability to fight infections. It can hinder patients’ ability to generate a robust response to COVID-19 vaccines.
Researchers investigated if pausing the drug for 2 weeks after a booster jab could improve the vaccine's protection. Interim results among 250 patients showed a 2 week break doubled patients COVID protection for up to 12 weeks. Levels of spike antibodies - which block the virus from infecting cells inside the body - were twice as high among patients who paused the drug.
This led to authorities in the UK and US changing their clinical guidelines.
Trial findings show protection lasts up to 6 months
Now the full trial findings from 383 participants show protection lasts for up to 6 months (1.5 times greater at 26 weeks than those who continued their treatment as usual).
These patients reported experiencing more flare-ups of their inflammatory conditions. But most flare ups were self-managed, and most didn’t need help from a healthcare provider.
The full results also showed blood from people pausing the drug was more effective at killing the Wuhan strain and the Omicron BA.1 COVID-19 variants.
The findings will be useful for national immunisation advisory committees, researchers say. It can help them better plan timings of vaccinations among vulnerable patients.
Chief Investigator, Professor Abhishek at the University of Nottingham and Honorary Consultant Rheumatologist at Nottingham University Hospitals NHS Trust, said: “COVID-19 has not gone away, and with the emergence of new variants, and vaccine hesitancy among patients, it is important to optimise durable protection in people who are susceptible to COVID-19. Evidence from our trial will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of vaccination against COVID-19.”
Professor Danny McAuley, Scientific Director for NIHR Programmes, said: “As winter approaches, millions of people with compromised immune systems are still vulnerable to becoming unwell from COVID-19, despite the disease being less prevalent than it once was.
“This important research provides even more high quality evidence that by managing medicines in relation to vaccinations we can keep patients healthier while reducing pressure on the NHS.”
Oxford Clinical Trials Research Unit (OCTRU) managed the trial. Experts at Manchester University, Imperial College London, University of Oxford and Queen Mary University London were also involved.
The Efficacy Mechanism Evaluation (EME) Programme funded the study. EME is an NIHR and MRC partnership. NIHR's Clinical Research Network (CRN) and Manchester Biomedical Research Centre (BRC) supported the trial.
The full results were published in the Lancet Rheumatology.