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08-03-2022 | COVID-19 | News

Temporary methotrexate withdrawal may improve COVID-19 vaccine immunogenicity

Author: Claire Barnard


medwireNews: Findings from the CoronavRheum trial suggest that suspension of methotrexate for 2 weeks after each dose of the Sinovac inactivated SARS-CoV-2 vaccine (CoronaVac) may improve antibody response rates to vaccination among people with rheumatoid arthritis (RA).

However, methotrexate withdrawal was associated with increased flare rates after the second vaccine dose, report Eloisa Bonfa and co-investigators from Universidade de Sao Paulo in Brazil.

The trial included 129 RA patients with low disease activity or remission (CDAI ≤10 points) who were on a stable methotrexate dose of at least 10 mg/week for at least 4 weeks, either as monotherapy or in combination with other agents. Participants received two doses of the Sinovac vaccine with a 4-week interval and were randomly assigned to either withdraw or maintain methotrexate for 2 weeks after each vaccine dose.

As reported in the Annals of the Rheumatic Diseases, the proportion of patients with seroconversion (anti-SARS-CoV-2 immunoglobulin G ≥15 AU/mL) at 6 weeks after the second vaccine dose was significantly higher in the methotrexate withdrawal group than in the control group, at 78.4% versus 54.5%.

In addition, rates of neutralizing antibody positivity – defined as neutralizing activity of at least 30% on a SARS-CoV-2 surrogate virus neutralization test – were numerically higher in the withdrawal than the control arm (62.2 vs 49.1%), but the between-group difference did not reach statistical significance.

Bonfa and team say that this increase in vaccine immunogenicity with methotrexate withdrawal was similar to that seen in a previous study of the immune response to influenza vaccination, and has the potential to “reduce the deleterious effects in [seroconversion] induced by [methotrexate] reported for the Sinovac-CoronaVac vaccine,” as well as for the Pfizer–BioNTech (BNT162b2) messenger RNA vaccine.

“Importantly, [methotrexate] dose was comparable between the groups and all patients had doses above 10 mg/week, in line with the observation that only patients with doses greater than 7.5 mg/week benefited from [methotrexate] withdrawal after influenza vaccine,” they add.

In spite of these immunogenicity benefits, patients who stopped methotrexate had significantly higher rates of flare (CDAI >10 points) 6 weeks after the second vaccine dose (31.7 vs 13.0%) and numerically, but not significantly, higher rates of flare at the time of the second dose (21.7 vs 11.6%).

“The increased flare rates after second [methotrexate] withdrawal may be due to the short-term interval between vaccine doses,” speculate the researchers.

They conclude that the methotrexate withdrawal strategy “requires close surveillance and shared decision making due to the possibility of disease activity worsening.”

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

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Ann Rheum Dis 2022; doi:10.1136/annrheumdis-2021-221916