@article {Araujo889, author = {Carlo Scognamiglio Renner Araujo and Ana Cristina Medeiros-Ribeiro and Carla G S Saad and Karina Rossi Bonfiglioli and Diogo Souza Domiciano and Andrea Yukie Shimabuco and Matheus Santos Rodrigues Silva and Emily Figueiredo Neves Yuki and Sandra Gofinet Pasoto and Tatiana Pedrosa and Leonard de Vinci Kanda Kupa and Gioanna Zou and Rosa M R Pereira and Cl{\'o}vis Artur Silva and N{\'a}dia Emi Aikawa and Eloisa Bonfa}, title = {Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial}, volume = {81}, number = {6}, pages = {889--897}, year = {2022}, doi = {10.1136/annrheumdis-2021-221916}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA).Methods This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) <=10, prednisone <=7.5 mg/day) randomised (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. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI \>10) and did not withdraw MTX twice.Results Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). 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\%), p=0.848) 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\%), p=0.019), with parallel augmentation in GMT (34.2 (25.2{\textendash}46.4) vs 16.8 (11.9{\textendash}23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2\%) vs 27 (49.1\%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI \>10 was more frequent in MTX-hold at D69 (p=0.024).Conclusion We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.All data relevant to the study are included in the article.}, issn = {0003-4967}, URL = {https://ard.bmj.com/content/81/6/889}, eprint = {https://ard.bmj.com/content/81/6/889.full.pdf}, journal = {Annals of the Rheumatic Diseases} }