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Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial.

Abhishek Abhishek, Prof; Boyton, Prof Rosemary J; Peckham, Nicholas; Áine McKnight, Prof; Coates, Laura C; Bluett, James; Barber, Vicki; Cureton, Lucy; Francis, Anne; Appelbe, Duncan; Eldridge, Lucy; Julier, Patrick; Valdes, Prof Ana M; Brooks, Tim; Rombach, Ines; Altmann, Prof Daniel M; Nguyen-Van-Tam, Prof Jonathan S; Williams, Prof Hywel C; Cook, Jonathan A; study investigators, VROOM; Hider, Samantha; Pande, Ira; Seng Tang, Ting; Tran, Gui; Layton, Alison; Price, Elizabeth; Whittam, Lindsay; Venkatachalam, Srinivasan; Hawarden, Ashley; Huws, Gwenan; Pratt, Arthur; Reynolds, Nick J; Walsh, David; Joseph, Theresa; Mathew, Rengi; Oikonomou, Stamatios; Gwynne, Catherine; Crowder, Rory; Saravanan, Vadivelu; Mustafa, Alaa; Tacu, Cristina; Batty, Thomas; George, Emmanuel; Soni, Anushka; Horton, Sarah; Madan, Ayesha; Gaffney, Karl; Lapin, Agnieszka; Bingham, Sarah; Levell, Nick; Lim, Edwin; Gullick, Nicola; Holroyd, Chris; Khalid, Salema; Lwin, May; Green, Mike; Hunt, Laura; Alcorn, Nicola...

Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial. Thumbnail


Authors

Prof Abhishek Abhishek

Prof Rosemary J Boyton

Nicholas Peckham

Prof Áine McKnight

Laura C Coates

James Bluett

Vicki Barber

Lucy Cureton

Anne Francis

Duncan Appelbe

Lucy Eldridge

Patrick Julier

Prof Ana M Valdes

Tim Brooks

Ines Rombach

Prof Daniel M Altmann

Prof Jonathan S Nguyen-Van-Tam

Prof Hywel C Williams

Jonathan A Cook

VROOM study investigators

Ira Pande

Ting Seng Tang

Gui Tran

Alison Layton

Elizabeth Price

Lindsay Whittam

Srinivasan Venkatachalam

Gwenan Huws

Arthur Pratt

Nick J Reynolds

David Walsh

Theresa Joseph

Rengi Mathew

Stamatios Oikonomou

Catherine Gwynne

Rory Crowder

Vadivelu Saravanan

Alaa Mustafa

Cristina Tacu

Thomas Batty

Emmanuel George

Anushka Soni

Sarah Horton

Ayesha Madan

Karl Gaffney

Agnieszka Lapin

Sarah Bingham

Nick Levell

Edwin Lim

Nicola Gullick

Chris Holroyd

Salema Khalid

May Lwin

Mike Green

Laura Hunt

Nicola Alcorn

Rob Ellis

Alaa Hassan

Taryn Youngstein

Karen Douglas

Gen Nen Ho

Kirsty Levasseur

Sara Treacy

Myrto Cheila

John Pradeep

Ceril Rhys-Dillon

Catrin Jones



Abstract

BACKGROUND: Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. METHODS: We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (=25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. FINDINGS: Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the continue methotrexate group and 127 in the suspend methotrexate group. Their mean age was 59·1 years, 155 (61%) were female, 130 (51%) had rheumatoid arthritis, and 86 (34%) had psoriasis with or without arthritis. After 4 weeks, the geometric mean S1-RBD antibody titre was 22?750 U/mL (95% CI 19?314-26?796) in the suspend methotrexate group and 10?798 U/mL (8970-12?997) in the continue methotrexate group, with a geometric mean ratio (GMR) of 2·19 (95% CI 1·57-3·04; p<0·0001; mixed-effects model). The increased antibody response in the suspend methotrexate group was consistent across methotrexate dose, administration route, type of immune-mediated inflammatory disease, age, primary vaccination platform, and history of SARS-CoV-2 infection. There were no intervention-related serious adverse events. INTERPRETATION: A 2-week interruption of methotrexate treatment for people with immune-mediated inflammatory diseases resulted in enhanced boosting of antibody responses after COVID-19 vaccination. This intervention is simple, low-cost, and easy to implement, and could potentially translate to increased vaccine efficacy and duration of protection for susceptible groups. FUNDING: National Institute for Health and Care Research.

Acceptance Date Jun 27, 2022
Publication Date Jun 27, 2022
Publicly Available Date Mar 28, 2024
Journal Lancet Respiratory Medicine
Print ISSN 2213-2600
Publisher Elsevier
Pages 840 - 850
DOI https://doi.org/10.1016/S2213-2600%2822%2900186-2
Publisher URL https://www.sciencedirect.com/science/article/pii/S2213260022001862

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