medwireNews: Pausing methotrexate only after the second dose of a COVID-19 vaccine may provide the best balance between antibody response and risk for flare, findings from two randomized controlled trials suggest.
Anu Sreekanth (Sree Sudheendra Medical Mission, Kochi, India), presenting the trial data at the EULAR 2022 Congress in Copenhagen, Denmark, commented that to improve immunogenicity “the ACR guidelines state to hold methotrexate for 1 to 2 weeks as disease activity allows after each COVID-19 vaccine dose but with a moderate level of evidence.”
But given the potential risk for flare, Sreekanth and colleagues considered whether pausing methotrexate only after the second dose may be sufficient to increase antibody response.
They conducted two studies – MIVAC I and MIVAC II – in unvaccinated patients with rheumatoid arthritis or psoriatic arthritis who had been on a stable dose of methotrexate for at least 6 weeks and a maximum prednisolone dose of 5 mg/day.
For the MIVAC I study, 80 patients stopped taking methotrexate for 2 weeks after each dose of the Oxford–AstraZeneca (ChAdOx1 nCoV-2019) vaccine, while 78 continued to take the medication.
The majority of patients were women aged a mean of 48–49 years and the average baseline methotrexate dose was 15.0–17.5 mg/week.
Median anti-receptor binding domain (RBD) antibody titers at 4 weeks were significantly higher for the patients who stopped methotrexate, at 2484 IU m/L compared with 1147 IU/mL in those who did not. However, Sreekanth noted that stopping methotrexate was also associated with an increased risk for flare at 4 weeks, defined as an increase in DAS28/cDAPSA scores to more than 1.2 or physician intent to increase DMARDs.
Specifically, 25% of patients stopping methotrexate had disease flare after the first vaccine dose, compared with 8% of those who continued methotrexate, a significant difference. The numbers were also increased when methotrexate was paused after the second vaccine dose, but the difference was not significant, at 23.8% compared with 13.3%, respectively.
Sreekanth reported that in the MIVAC II study, median anti-RBD titers in 76 patients who withheld methotrexate for 2 weeks only after the second vaccine dose were still significantly higher than in 81 patients who continued treatment (2553 vs 990 IU/mL), and they did not have a significantly increased risk for flare (11.8 vs 7.9%).
As the studies were parallel in nature and conducted in a similar population, the researchers compared the two groups of patients who withheld methotrexate and found no significant difference in anti-RBD titers.
But there was a significant increase in flare rates among patients who paused treatment after both vaccine doses, at 36.25% versus 11.84% among those who did so only after the second dose.
Sreekanth concluded: “Holding methotrexate only after the second dose appears to be non-inferior to holding methotrexate after both the doses of the vaccine, with a lesser risk of flare.”
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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EULAR 2022; Copenhagen, Denmark: 1–4 June
Ann Rheum Dis 2022; 81: 208–209