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The study was planned to recruit 560 patients but recruitment was stopped early by the independent study oversight committees when interim results from the first 254 participants showed a clear result.
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While methotrexate is effective at controlling autoimmune conditions and has emerged as first line therapy for many other illnesses, it reduces the body’s ability to fight infections and the ability to generate robust response to flu and pneumonia vaccines, including those against COVID-19.
Patients older than 18 years in age were recruited from dermatology and rheumatology outpatients in 26 NHS hospitals across England and Wales. The trial evaluated temporarily stopping versus continuing methotrexate treatment immediately after the third-prime dose or booster of the COVID-19 vaccine.
127 participants were asked to suspend methotrexate use for two weeks and 127 to continue using it as usual. The decision on who stopped or continued with methotrexate treatment was made by a computer program – similar to tossing a coin or rolling a dice.
The team 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 blocks the virus from infecting cells inside the body.
Effect of Stopping Methotrexate:
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.
There was a worsening of disease control at week 4 in the suspend group, but that had normalized by week 12. There was no impact on quality of life or general health.
The independent study steering committee advised to stop further recruitments into the VROOM trial. Participants who took part in the VROOM study are being invited to participate in an additional visit six months after their vaccination date.
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.
Chief Investigator, Professor Abhishek 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 hospitalizations 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.
Professor Andy Ustianowski, 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.”
Joint lead applicant Professor Rosemary Boyton said: “This study is the first to report the effectiveness of a two-week interruption of an immunosuppressant drug called methotrexate immediately after COVID-19 booster vaccination to enhance antibody binding immunity against SAR-CoV-2.
Our results showed a doubling of antibody levels, an increase that was sustained at 12 weeks. This has important implications for future vaccination strategy in this immunosuppressed patient group.”
OCTRU Academic Lead, Jonathan Cook said: “It’s pleasing to see the difference that a simple, cheap and modest adjustment to treatment can make.
Clinical trials like VROOM are needed to help us understand how best to deliver vaccinations like a COVID-19 booster in different patient groups.”
Professor John Iredale, Executive Chair of the Medical Research Council, which part-funded the trial, said: “This important finding means many people who need to take immune-suppressing medicines now have a safe and effective way to improve their immune response to life-saving COVID-19 vaccines.
This study shows yet again how the UK research community’s world-leading ability to rapidly set up well-designed clinical trials can deliver the evidence needed to optimize medical interventions and save lives in the pandemic.”
Source: Medindia
