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Major COVID-19 booster trial looks at how best to improve immunity against coronavirus in vulnerable people

Researchers have launched a major clinical trial investigating whether people on long-term immune-suppressing medicines can mount a more robust immune response to COVID-19 booster jabs by interrupting their treatment.

The VROOM trial will have implications for people on immune-suppressing medicines, who are among the millions of clinically vulnerable patients advised to ‘shield’ during the pandemic. The study is funded by an NIHR and the Medical Research Council (MRC) partnership, and led by a team at the University of Nottingham.

Approximately 1.3 million people in the UK are prescribed the immune-suppressing drug methotrexate for inflammatory conditions such as rheumatoid arthritis, and skin conditions such as psoriasis. Many of them were among the 2.2 million clinically extremely vulnerable people advised to shield during the first phase of the pandemic, depending on specialist advice and on their risk factors.

While methotrexate is effective at controlling these conditions and has emerged as first line therapy for many illnesses, it reduces the body’s ability to generate robust responses to flu and pneumonia vaccines.

Researchers will recruit 560 patients currently taking methotrexate, to investigate whether taking a two week break in this drug immediately after they receive the COVID-19 booster jab improves their immune response to vaccination, while preventing flare-ups of their long-term illness. The study will take between one to two years to complete. All participants will have had the Pfizer-BioNTech vaccine as their third jab, as part of the national vaccination programme against COVID-19.

Better immunity usually means a better chance of avoiding infection in the first place, and fighting the virus if people are infected. Statistics show that people with inflammatory conditions are 1.2 to 1.3 times more likely to die or be hospitalised from COVID-19.

A previous study from Korea showed that a two-week ‘treatment holiday’ from methotrexate after the flu vaccine increased the patients’ immune response to that vaccine. But it isn’t known if such an interruption in treatment would improve the protection provided by vaccines against COVID-19. This means that during the COVID-19 vaccine rollout specialists across the world have given conflicting advice that has confused patients. 

The COVID-19 booster jab rollout gives an opportunity to answer this question. 

Chief Investigator Professor Abhishek, Professor of Rheumatology at the University of Nottingham and Honorary Consultant Rheumatologist at Nottingham University Hospitals NHS Trust, said: “People with inflammatory conditions such as rheumatoid arthritis and skin diseases such as psoriasis face a daily battle dealing with painful and troubling effects of their illness. This can leave them unable to carry out daily tasks independently. At the same time, they face a double-edged sword of being more vulnerable to COVID-19, while potentially unable to mount the strongest possible immune response to vaccines against COVID-19, to protect them from the virus following their jab, leaving many of them still fearing the virus.

“We hope to find out whether they can safely take a break from medications for their inflammatory conditions and an improved protection from the booster jab, without the risk of flare-up of their long-term illness which affects their daily lives so heavily.

“Many people take methotrexate for more than 10-20 years, so we hope to provide high quality evidence which can help them with their day to day lives going forward.”

Professor Andy Ustianowski, NIHR Clinical Lead for the COVID-19 Vaccination Programme and Joint National Infection Specialty Lead, said: “Although the vaccine rollout has saved many lives and helped drive down the effects of the pandemic, there are still groups of vulnerable people who can’t always mount robust immunity against the virus. 

“It’s important to establish if people can safely improve protection from their booster jabs by taking a break from their immune-supressing medicines, and this pivotal study will help develop our understanding of immune responses in people taking this widely prescribed medicine.

“Once again NIHR is providing a critical role in the fight against COVID-19, funding ground-breaking research, while volunteers are participating in trials to help us learn more and ultimately beat the virus.”

The study is funded through the Efficacy and Mechanism Evaluation (EME) Programme - an NIHR and MRC partnership.

The study is being delivered in partnership with Oxford Clinical Trials Research Unit (OCTRU), Oxford University and is running in over 20 hospitals in the UK, supported by the NIHR’s Clinical Research Network (CRN)

More information is available on the study’s project page and on the study website

Annabelle’s story

Annabelle Imray, 48, who lives in Chilwell, Nottingham, with her family, is taking part in the VROOM trial. 

Mrs Imray, who is married with three children, lives with psoriatic arthritis, something she describes as “life-changing”.

This means living with swollen joints and varying degrees of pain – from a “dull ache” to acute pain, walking at a slow pace and having dry, flaky skin. At times, she feels so tired because of her condition she has to plan her days carefully.

Although Mrs Imray initially shielded during the early stages of the pandemic, she later adapted her lifestyle to cut the risk of being infected by COVID-19. This included choosing quieter times of the day to go shopping and switching her teaching job to online sessions from physical classes.

She said: “Despite things opening up following lockdowns, there’s still uncertainty and anxiety for me about the virus and I have to be cautious.

“I explain to the kids that if I catch COVID-19 I’m much more likely to be seriously ill than them. When they return home I used to immediately tell them to wash their hands before they come too close to me. The whole family needs to take precautions other people may not take and be careful about going out. Our way of life has become much more insular.

“When I do go out, I’m worried walking close to strangers, or if someone is coughing without a mask I would be worried about the potential of catching something. 

“Hopefully the trial will make a big difference for people on immune suppressing medicines giving reassurance and confidence to do things they enjoy in their lives and know that we are more protected. It’s the uncertainty that is the worst.”