Suspending methotrexate therapy shown to improve COVID booster response

Findings from a recent study showed that a two-week interruption in methotrexate therapy in people with immune-mediated inflammatory disease more than doubled their antibody response following COVID-19 vaccination.

Close-up image of a COVID-19 antibody
The antibody response to a COVID-19 vaccine booster dose was significantly greater in people who suspended methotrexate therapy for two weeks than in those who continued treatment. | GETTY IMAGES

The Vaccine Response On/Off Methotrexate (VROOM) study was an open-label, randomised controlled study including 254 adults with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis, atopic dermatitis) who had been prescribed methotrexate (≤25mg/week orally or subcutaneously) for at least the previous three months, with or without hydroxychloroquine, and who were eligible to receive a third COVID-19 vaccine dose.

Participants were randomised to either suspend methotrexate therapy for two weeks (n=127) immediately following a COVID-19 vaccine booster dose or to continue treatment as usual (n=127).

Antibody response

At four weeks, the antibody response against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein was significantly greater in patients in the suspend methotrexate group compared with those in the continue methotrexate group (geometric mean titre [GMT] 22,750 U/mL vs 10,798 U/mL, respectively).

After adjusting for baseline value, randomisation factors, previous COVID infection, and booster vaccine platform used, the geometric mean ratio (GMR) of S1-RBD antibody responses between the two groups was 2.19 (95% CI 1.57-3.04; p<0.0001).

Sustained response

S1-RBD antibody titres remained significantly higher in the suspend methotrexate group than in the continue methotrexate group at week 12 (GMT 16,520 U/mL versus 8,094 U/mL; GMR 2.11 [95% CI 1.51-2.94; p<0.0001]).

The researchers report that quality of life or general health was not impacted by the interruption in methotrexate therapy. A temporary deterioration in self-reported disease activity and self-reported disease control was observed at week 4 with resolution at week 12.

They add that their findings suggest easy implementation in the real world for patients who are willing to pause methotrexate treatment for two weeks and for whom the clinician managing the condition feels it reasonable to interrupt treatment without adverse impact on the disease course.

Further research needed

The researchers conclude that further research is needed to ascertain whether interrupting treatment with other similarly acting immunosuppressive drugs will also enhance vaccine-induced immunity.

Commenting on the findings, Professor Abhishek, honorary consultant rheumatologist at Nottingham University Hospitals NHS Trust and lead study author said: "Implementing these results could vastly improve the protection provided by boosters against COVID-19 for millions of people living with these [inflammatory] 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."

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