POS0259 A RANDOMIZED CLINICAL TRIAL OF 2-WEEK METHOTREXATE DISCONTINUATION IN RHEUMATOID ARTHRITIS PATIENTS VACCINATED WITH INACTIVATED SARS-COV-2 VACCINE

Abstract

Background: Patients with rheumatoid arthritis (RA) on methotrexate have reduced vaccine responses. Temporary discontinuation has improved immuno‐genicity of anti‐infuenza vaccine, but this strategy has not been evaluated in anti‐SARS‐CoV‐2 vaccines. Objectives: 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 rheumatoid arthritis (RA) patients. Methods: This was a single‐center, prospective, randomized, investigator‐blinded, intervention study (#NCT04754698, CoronavRheum), including adult RA patients (stable CDAI≤10, prednisone ≤7.5mg/day), randomized (1:1) to withdraw MTX (MTX‐hold) for 2 weeks after each vaccine dose or maintain MTX (MTX‐maintain), evaluated at D0, D28 and D69. Co‐primary outcomes were anti‐SARS‐CoV‐2 S1/S2 IgG seroconversion(SC) and neutralizing antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titers (GMT) and fare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and, for safety reasons, those who fared at D28 (CDAI>10) and did not withdraw MTX twice. Results: Randomization included 138 patients with 9 exclusions (5 COVID‐19, 4 protocol violations). Safety evaluation included 60 (MTX‐hold) and 69 (MTX‐maintain) patients. Further exclusions: 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, MTX‐hold (n=37) had a higher rate of seroconversion than MTX‐maintain (n=55) group [29 (78.4%) vs 30 (54.5%), p=0.019], with parallel augmentation in GMT [34.2 (25.2‐46.4) vs 16.8 (11.9‐23.6), p=0.006]. No differences were observed for NAb positivity [23 (62.2%) vs 27 (49.1%), p=0.217]. At D28 fare, rates were comparable in both groups (CDAI, p=0.122; DAS28‐CRP, p=0.576), whereas CDAI>10 was more frequent in MTX‐hold at D69 (p=0.024). Conclusion: We provide novel data that 2‐week MTX withdrawal after each Sinovac‐CoronaVac vaccine dose improves anti‐SARS‐CoV‐2 IgG response. The increased fare rates after 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 fares.