03 November 2022
Patients treated with low-dose weekly methotrexate can optimise their vaccine-induced immunity with a two-week temporary suspension in methotrexate treatment immediately after vaccination against COVID-19. Writing in the journal Lancet Respiratory Medicine, Abhishek and colleagues reported initial findings of the Vaccine Response On Off Methotrexate (VROOM) Study, a clinical trial funded by NIHR and MRC that recruited patients with Immune-Mediated Inflammatory Diseases (IMIDs) from rheumatology and dermatology clinics in 26 NHS hospitals.
As a result of the studies’ findings, BSR issued guidance:
“In response to the VROOM Study, adult rheumatology patients who are stable on methotrexate may consider stopping methotrexate after booster vaccination for COVID-19 for two weeks (skipping 2 doses of methotrexate). There is no need to stop prior to vaccination. There is a small risk of flare. This has been shown to improve vaccine response to COVID-19.”
Ahead of the autumn 2022 COVID-19 booster vaccination programme, clinicians will want to be aware of the implications of this study on their patients treated with methotrexate.
Who took part in the study?
Adults with well-controlled IMIDs (e.g. RA, psoriasis +/- arthritis, SLE, etc.) prescribed either oral or subcutaneous methotrexate (with or without hydroxychloroquine) for at least three months, and having received two prior COVID-19 vaccinations were eligible to participate.
Key exclusion criteria included diseases for which treatment cannot be interrupted safely. Study participants were individually randomised to either suspend methotrexate for two weeks or continue as usual after booster vaccination against COVID-19.
What were the key findings?
The S1-RBD antibody response was 2.2-fold and 2.1-fold higher in the suspend methotrexate group than in the continue methotrexate group at week four (geometric mean titre [GMT] 22,750 vs 10,798 U/mL) and week 12 (GMT 16,520 vs 8,094 U/mL) respectively. There was an improved boosting of vaccine-induced immunity with a two-week break in treatment across age groups, methotrexate doses, administration routes, rheumatic and skin disease, primary vaccination platform, and prior SARS-CoV-2 infection status.
General health and quality of life were similar between the two groups at all time points. However, self-reported disease activity and disease control since vaccination were significantly worse at four weeks in the suspend methotrexate group than in the continue methotrexate group; activity was similar in the two groups by week 12. Significantly more participants self-reported at least one disease flare in the suspend methotrexate group than in the continue methotrexate group over the 12-week study period (71% vs 45%). However, most flares were self-managed, with only 14% of participants in the suspend methotrexate group, and 11% in the continue methotrexate group seeking NHS help for flare management respectively.
What is the key take home message?
A two week break in methotrexate treatment immediately after vaccination against COVID-19 improved vaccine-induced immunity. This could potentially translate to greater vaccine efficacy and longer duration of protection for vulnerable people with IMIDs.
Does this interruption in medication put patients at increased risk?
There was an increased risk of disease flare-up, which was mostly self-managed. Clinicians and patients should balance the possible risk of flare-ups versus the benefit of enhanced protection against COVID-19, taking patient preference, disease control, and experience of prior treatment interruptions into account.
The VROOM study participants are attending a week 26 visit to evaluate the long-term impact of break-in treatment on vaccine-induced immunity and disease control.
Finally, anything else?
Similar findings have been reported in other clinical trials in the context of vaccination against COVID-19 or seasonal influenza. Whether a temporary break from treatment would prevent COVID-19 or its complications was not evaluated in the VROOM study, as this was a relatively small study.