TY - JOUR
T1 - Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): A randomised, open label, superiority trial
AU - Abhishek, Abhishek
AU - Peckham, Nicholas
AU - Pade, Corinna
AU - Gibbons, Joseph M.
AU - Cureton, Lucy
AU - Francis, Anne
AU - Barber, Vicki
AU - Williams, Jennifer A. E.
AU - Appelbe, Duncan
AU - Eldridge, Lucy
AU - Julier, Patrick
AU - Altmann, Daniel M.
AU - Bluett, James
AU - Brooks, Tim
AU - Coates, Laura C.
AU - Rombach, Ines
AU - Semper, Amanda
AU - Otter, Ashley
AU - Valdes, Ana M.
AU - Nguyen-Van-Tam, Jonathan S.
AU - Williams, Hywel C.
AU - Boyton, Rosemary J.
AU - McKnight, Áine
AU - Cook, Jonathan A.
AU - Pande, Ira
AU - Tang, Ting Seng
AU - Tran, Gui
AU - Layton, Alison
AU - Price, Elizabeth
AU - Whittam, Lindsay
AU - Venkatachalam, Srinivasan
AU - Huws, Gwenan
AU - Pratt, Arthur
AU - Reynolds, Nick J.
AU - Youngstein, Taryn
AU - Walsh, David A.
AU - Joseph, Theresa
AU - Mathew, Rengi
AU - Oikonomou, Stamatios
AU - Gwynne, Catherine
AU - Crowder, Rory
AU - Saravanan, Vadivelu
AU - Mustafa, Alaa
AU - Tacu, Cristina
AU - George, Emmanuel
AU - Batty, Thomas
AU - Soni, Anushka
AU - Horton, Sarah
AU - Gaffney, Karl
AU - Lapin, Agnieszka
AU - VROOM study investigators
N1 - Funding Information: The study was funded by the NIHR–EME programme. Grant number: NIHR134607. Support was also received from the NIHR Oxford Biomedical Research Centre. The views expressed in this manuscript are those of its authors and not necessarily those of the National Health Service, NIHR, Department of Health and Social Care, or the Joint Committee on Vaccination and Immunisation. The study is sponsored by The University of Nottingham, Nottingham, UK and is managed by the Oxford Clinical Trials Research Unit (OCTRU). The co-authors would like to acknowledge the contribution of patient and public involvement volunteers in Oxford and Nottingham for their help in designing this study and members of OCTRU who enabled the rapid set-up of this study and have provided ongoing support.
© 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2024/2
Y1 - 2024/2
N2 - Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research.
AB - Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research.
UR - http://www.scopus.com/inward/record.url?scp=85179809166&partnerID=8YFLogxK
U2 - 10.1016/S2665-9913(23)00298-9
DO - 10.1016/S2665-9913(23)00298-9
M3 - Article
AN - SCOPUS:85179809166
VL - 6
SP - e92-e104
JO - The Lancet Rheumatology
JF - The Lancet Rheumatology
SN - 2665-9913
IS - 2
ER -
