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VROOM trial: Pausing methotrexate doubles antibody response to COVID-19 booster vaccine

Author: Claire Barnard

medwireNews: Holding methotrexate treatment for 2 weeks following administration of a booster dose of vaccines against SARS-CoV-2 significantly improves the humoral immune response to vaccination, suggest findings from a randomized controlled trial.

Speaking to medwireNews, VROOM co-investigator Rosemary Boyton (Guy’s and St Thomas’ National Health Service Foundation Trust, London, UK) said that the “most remarkable” finding from the trial is that the enhanced antibody response, first measured at 4 weeks, was sustained at the 12-week follow-up.

She explained that ani-SARS-CoV-2 antibody responses typically wane after a booster vaccine, so slowing this process is “a very, very encouraging outcome for these patients because it means they’ve got a sustained boosting response.”

The UK trial included 254 people on low-dose methotrexate treatment (≤25 mg/week) for rheumatic or dermatologic immune-mediated inflammatory diseases who had received two primary doses of a COVID-19 vaccine and were due to receive a booster dose. The most common diagnosis was rheumatoid arthritis (51.2%), followed by psoriasis with arthritis (20.5%), and other diseases included spondyloarthritis, polymyalgia rheumatica, and systemic lupus erythematosus. The majority of participants received the Oxford–AstraZeneca (ChAdOx1 nCoV-2019) vaccine for their two primary doses and Pfizer–BioNTech (BNT162b2) for their booster vaccine.

Abhishek Abhishek (University of Nottingham, UK) and colleagues report in The Lancet Respiratory Medicine that titers of antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein at 4 weeks after receipt of the booster dose were twofold higher among people who were randomly assigned to suspend methotrexate for 2 weeks immediately after receiving their booster vaccine than in those who continued treatment as usual. The geometric mean titers in these groups were 22,750 and 10,798 U/mL, respectively, a significant difference.

The investigators note that these findings remained consistent across subgroups including when patients were categorized by methotrexate dose, route of administration, inflammatory disease diagnosis, and previous SARS-CoV-2 infection.

At the 12-week follow-up, geometric mean anti-RBD titers remained significantly higher among participants who suspended methotrexate relative to those in the control arm, at 16,520 versus 8094 U/mL.

“This intervention is simple, low-cost, and easy to implement, and could potentially translate to increased vaccine efficacy and duration of protection for susceptible groups,” write Abhishek and team.

They caution, however, that these benefits came at the cost of an increased flare risk, with a significantly higher proportion of patients in the methotrexate suspension than the control group self-reporting flares during the 12 weeks following booster vaccination (71 vs 45%).

Abhishek told medwireNews that this “increased risk of disease flare must be borne in mind, but mostly these flares appear to be mild, not requiring [medical] help, and being self-managed.” A total of 14% of patients with methotrexate suspension and 11% of those continuing methotrexate sought assistance for flare management over the 12-week period.

The investigators conclude that their findings “will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics.”

Commenting on the VROOM trial in an accompanying article, Jeffrey Sparks and Sara Tedeschi, both from Brigham and Women’s Hospital in Boston, Massachusetts, USA, say that the results “extend previous findings showing that interruption of methotrexate improves vaccine immunogenicity,” and suggest that this may be “broadly applicable across different vaccine types.”

Nevertheless, they stress that “the precise threshold of humoral response necessary for protection against COVID-19 is unclear,” highlighting the need for further research.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

30 June 2022: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Lancet Respir Med 2022; doi:10.1016/S2213-2600(22)00186-2
Lancet Respir Med 2022; doi:10.1016/S2213-2600(22)00224-7

Image Credits: © Gilnature / Getty Images / iStock

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Lucy Piper

medwireNews Bureau Chief