A major clinical trial, involving researchers from Queen Mary University of London and led by the University of Nottingham, has found that by interrupting the treatment of vulnerable people on long-term immune suppressing medicines for two weeks after a COVID-19 booster vaccination, their antibody response to the jab is doubled.
The Vaccine Response On Off Methotrexate (VROOM) trial, which will have implications for people on immune-supressing medicines, who are among the millions of clinically vulnerable patients advised to ‘shield’ during the pandemic – is funded by the National Institute for Health and Care Research and the Medical Research Council.
The results of the study are published in The Lancet Respiratory Medicine.
The VROOM trial looked at the impact of interrupting methotrexate treatment for two-weeks after a COVID-19 booster vaccination on vaccine responses in adults with autoimmune inflammatory conditions. Methotrexate is the most commonly used immune-suppressing drug, with around 1.3 million people in the UK prescribed this medicine for inflammatory conditions such as rheumatoid arthritis, and skin conditions such as psoriasis.
The trial evaluated temporarily stopping versus continuing methotrexate treatment immediately after the third-prime dose or booster of the COVID-19 vaccine.
The researchers involved, spanning several major universities, compared the spike-antibody levels between the two groups four weeks and twelve weeks after they had received a COVID-19 vaccine dose. The spike-antibody, which reflects the strength of the antibody response, blocks the virus from infecting cells inside the body.
After 4 weeks and 12 weeks, the spike-antibody level was more than two-fold higher in the group where methotrexate was suspended for two-weeks following vaccination, compared to the group who continued use.
The spike-antibody level reflects the strength of the antibody response. The research team are currently examining the quality of the antibody response by measuring its ability to kill live SARS-CoV-2 viruses and other variants of concern such as Omicron.
Prof Áine McKnight, Professor of Viral Pathology at Queen Mary’s Blizard Institute, is one of the Investigators on the VROOM trial. Dr Joseph Gibbons and Dr Corinna Pade are part of the Queen Mary team working on this research.
Dr Joseph Gibbons said: "These are really important findings for the hundreds of thousands of vulnerable patients who are on immune suppressing treatments. We now know that temporarily interrupting treatment in this way can enhance antibody levels after the booster without reducing the patient’s quality of life. The improved response is very exciting to see for those who had suspended methotrexate treatment, but the results also highlight the benefit of getting boosted for everyone.
“The next phase of this study will be critical. At Queen Mary, we are investigating the quality of this elevated immune response by assessing the effectiveness of these additional antibodies against circulating strains of the virus. We are looking to see how effective these antibodies are at blocking the virus from entering our cells to get a better idea of whether the improvement will reduce COVID infections and disease severity.”
Dr Corinna Pade said: "The promising initial results on the effectiveness of COVID vaccine boosting following suspension of methotrexate paves the way to better understanding the immune responses in immunosuppressed individuals. Here at Queen Mary, extended studies on neutralising antibody capabilities will now show how the immune system of these patients might handle live SARS-CoV-2 such as the Omicron variant and whether the quality of antibodies matches the strength of spike antibody levels.”
The study was planned to recruit 560 patients, but recruitment was stopped early by the independent study oversight committees when the interim results from the first 254 participants showed such a clear picture.
Chief Investigator, Professor Abhishek at the University of Nottingham and Honorary Consultant Rheumatologist at Nottingham University Hospitals NHS Trust, said: “We are extremely pleased with the initial results of the VROOM trial. There was a doubling of the antibody response in patients who held off on taking methotrexate for two weeks. The improvement in antibody response was maintained over a 3-month period. There was a short-term increase in risk of flare-up of inflammatory conditions. However, most could be self-managed.
“We also saw no adverse impact on the quality of patient’s life following suspension of their medication. However, the study did not evaluate whether this strategy would result in fewer cases of COVID-19 or fewer hospitalisations due to COVID-19 as it was not large enough to detect these differences.
"Implementing these results could vastly improve the protection provided by boosters against COVID-19 for millions of people living with these conditions. COVID-19 has left them vulnerable to serious illness, whilst still having to live with the painful and troubling effects of their conditions. We hope this evidence is the next step in helping them with their lives going forward.”
Professor Andy Ustianowski, NIHR Clinical Lead for the COVID-19 Vaccine Research Programme and Joint National Infection Specialty Lead, said: “Despite the majority of the UK population now being vaccinated, it remains as important as ever to continue ongoing research to ensure we can use vaccines effectively in different groups of patients.
“These landmark results provide high quality evidence to help best protect millions of people with compromised immune systems, keeping them safer from the virus and their existing chronic conditions.
“Thank you to all the participants who took part, we rely on their continued commitment to help us learn more and ultimately beat the virus.”
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