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
Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
The Lancet. Rheumatology - 6(2024), 2 vom: 01. Jan., Seite e92-e104 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abhishek, Abhishek [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 Vaccines |
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| Anmerkungen: |
Date Completed 26.01.2024 Date Revised 26.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/S2665-9913(23)00298-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study) |b a randomised, open label, superiority trial |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a FUNDING: National Institute for Health and Care Research | ||
| 650 | 4 | |a Randomized Controlled Trial | |
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| 650 | 7 | |a Methotrexate |2 NLM | |
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| 700 | 1 | |a Barber, Vicki |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Jennifer A E |e verfasserin |4 aut | |
| 700 | 1 | |a Appelbe, Duncan |e verfasserin |4 aut | |
| 700 | 1 | |a Eldridge, Lucy |e verfasserin |4 aut | |
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| 700 | 1 | |a Coates, Laura C |e verfasserin |4 aut | |
| 700 | 1 | |a Rombach, Ines |e verfasserin |4 aut | |
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| 700 | 1 | |a Boyton, Rosemary J |e verfasserin |4 aut | |
| 700 | 1 | |a McKnight, Áine |e verfasserin |4 aut | |
| 700 | 1 | |a Cook, Jonathan A |e verfasserin |4 aut | |
| 700 | 0 | |a VROOM study investigators |e verfasserin |4 aut | |
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| 700 | 1 | |a Tang, Ting Seng |e investigator |4 oth | |
| 700 | 1 | |a Tran, Gui |e investigator |4 oth | |
| 700 | 1 | |a Layton, Alison |e investigator |4 oth | |
| 700 | 1 | |a Price, Elizabeth |e investigator |4 oth | |
| 700 | 1 | |a Whittam, Lindsay |e investigator |4 oth | |
| 700 | 1 | |a Venkatachalam, Srinivasan |e investigator |4 oth | |
| 700 | 1 | |a Huws, Gwenan |e investigator |4 oth | |
| 700 | 1 | |a Pratt, Arthur |e investigator |4 oth | |
| 700 | 1 | |a Reynolds, Nick J |e investigator |4 oth | |
| 700 | 1 | |a Youngstein, Taryn |e investigator |4 oth | |
| 700 | 1 | |a Walsh, David A |e investigator |4 oth | |
| 700 | 1 | |a Joseph, Theresa |e investigator |4 oth | |
| 700 | 1 | |a Mathew, Rengi |e investigator |4 oth | |
| 700 | 1 | |a Oikonomou, Stamatios |e investigator |4 oth | |
| 700 | 1 | |a Gwynne, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Crowder, Rory |e investigator |4 oth | |
| 700 | 1 | |a Saravanan, Vadivelu |e investigator |4 oth | |
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| 700 | 1 | |a Tacu, Cristina |e investigator |4 oth | |
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| 700 | 1 | |a Bingham, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Madan, Ayesha |e investigator |4 oth | |
| 700 | 1 | |a Holroyd, Chris |e investigator |4 oth | |
| 700 | 1 | |a Lwin, May |e investigator |4 oth | |
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