Journal Article

Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial

Pedrosa, Tatiana, Aikawa, Nádia Emi, Silva, Clóvis Artur, Yuki, Emily Figueiredo Neves, Pasoto, Sandra Gofinet, Araujo, Carlo Scognamiglio Renner, Medeiros-Ribeiro, Ana Cristina, Shimabuco, Andrea Yukie, Domiciano, Diogo Souza, Bonfiglioli, Karina Rossi, Pereira, Rosa M R, Zou, Gioanna, Silva, Matheus Santos Rodrigues, Saad, Carla G S, Bonfa, Eloisa, Kupa, Leonard de Vinci Kanda

2022

Overview

ObjectiveTo 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).MethodsThis 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.ResultsRandomisation 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 (25.2–46.4) 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 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).ConclusionWe 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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Adult / Antibodies, Neutralizing / Antibodies, Viral / arthritis / Arthritis, Rheumatoid - drug therapy / C-reactive protein / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 vaccines / COVID-19 Vaccines - administration & dosage / Decision making / Disease / Drug dosages / Drug withdrawal / Epidemiology / Hospitalization / Humans / Immunogenicity / Immunoglobulin G / Influenza / Joint diseases / Laboratories / Life sciences / Medical research / Methotrexate / Methotrexate - administration & dosage / Methotrexate - therapeutic use / Patients / Prednisone / Prospective Studies / Remission (Medicine) / Researchers / rheumatoid / Rheumatoid arthritis / Rheumatology / Safety / SARS-CoV-2 / Seroconversion / Serology / Severe acute respiratory syndrome coronavirus 2 / Shared decision making / Surveillance / vaccination / Vaccines / Withholding Treatment