Orthopaedics Medicine

MTX Withdrawal After COVID-19 Vaccination Improves Immunogenicity In RA Patients But At A Cost

• byDoctor News Daily Team
• 18 February, 2025
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Brazil: Data from a recent study revealed that 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 immunogenicity in patients with rheumatoid arthritis (RA). The strategy, however, was associated with higher flare rates following the second dose of the vaccine and may be attributed to the short-term interval between vaccine doses. The study appears in the BMJ journal Annals of the Rheumatic Diseases.

It is known that in rheumatoid arthritis patients, temporary MTX withdrawal for 2 weeks following the influenza vaccine improves immunogenicity without worsening disease activity.
Considering the above, Eloisa Bonfa, Rheumatology Division, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, Brazil, and colleagues aimed to evaluate the effect on immunogenicity and safety of 2-week MTX discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in RA patients in a single-center, prospective, randomized, investigator-blinded, intervention study.
The study included adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day). They were randomized in a ratio of 1:1 to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28, and D69.
Anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69 were the coprimary outcomes. Secondary outcomes were geometric mean titres (GMT) and flare rates. Patients with baseline positive IgG/NAb were excluded for immunogenicity analyses, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice.
Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations).
Based on the study, the researchers found the following:
Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group.
Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%)) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28.
At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%)), with parallel augmentation in GMT (34.2 vs 16.8).
No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%)).
At D28 flare, the rates were comparable in both groups (CDAI; Disease Activity Score in 28 joints with C reactive protein), whereas CDAI >10 was more frequent in MTX-hold at D69).
The researchers conclude, this study provides novel data that 2-week MTX withdrawal after each vaccine dose improves anti-SARS-CoV-2 IgG response to the Sinovac-CoronaVac vaccine.
"The increased flare rates following the second MTX withdrawal may be due to the short-term interval between vaccine doses," the authors wrote. "This strategy requires close surveillance and shared decision making due to the possibility of disease activity worsening."
Reference:
Araujo CSR, Medeiros-Ribeiro AC, Saad CGS, et alTwo-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trialAnnals of the Rheumatic Diseases Published Online First: 22 February 2022. doi: 10.1136/annrheumdis-2021-221916