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. 2025 Jun;91(6):1586-1599.
doi: 10.1111/bcp.16062. Epub 2024 Apr 8.

OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate

Andrew D Brown  1 , Louis Fisher  1 , Helen J Curtis  1 , Milan Wiedemann  1 , William J Hulme  1 , Victoria Speed  1 , Lisa E M Hopcroft  1 , Christine Cunningham  1 , Ruth E Costello  2 , James B Galloway  3 , Mark D Russell  3 , Katie Bechman  3 , Zeyneb Kurt  4 , Richard Croker  1 , Chris Wood  1 , Alex J Walker  1 , Andrea L Schaffer  1 , Seb C J Bacon  1 , Amir Mehrkar  1 , George Hickman  1 , Chris Bates  5 , Jonathan Cockburn  5 , John Parry  5 , Frank Hester  5 , Sam Harper  5 , Ben Goldacre  1 ; OpenSAFELY Collaborative; Brian MacKenna  1
Affiliations

OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate

Andrew D Brown et al. Br J Clin Pharmacol. 2025 Jun.

Abstract

Aims: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic.

Methods: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations.

Results: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study.

Conclusion: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups.

Keywords: COVID‐19; antirheumatic agents; azathioprine; electronic health records; general practice; leflunomide; methotrexate.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. B.G. has received research funding from the Laura and John Arnold Foundation, the NHS National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Mohn‐Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, the World Health Organisation, UKRI, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he also receives personal income from speaking and writing for lay audiences on the misuse of science. B.M.K. is employed by NHS England working on medicines policy and clinical lead for primary care medicines data. C.B., J.C., J.P., F.H. and S.H. are employees of TPP.

Figures

FIGURE 1
FIGURE 1
Proportion of patients overdue monitoring between November 2019 and July 2022, broken down by shared care medication. The baseline period before lockdown is shown as an orange dashed vertical line. The monitoring window, measured as 3 months from the onset of the March 2020 COVID‐19 lockdown, is shown as a green dashed vertical line.
FIGURE 2
FIGURE 2
Proportions of patients overdue disease‐modifying antirheumatic drug (DMARD) monitoring between November 2019 and July 2022, broken down by monitoring test type. The baseline period before lockdown is shown as an orange dashed vertical line. The monitoring window, measured as 3 months from the onset of the March 2020 COVID‐19 lockdown, is shown as a green dashed vertical line.
FIGURE 3
FIGURE 3
Practice level decile charts for proportions of patients overdue disease‐modifying antirheumatic drug (DMARD) monitoring between November 2019 and July 2022.
FIGURE 4
FIGURE 4
Proportions of patients overdue disease‐modifying antirheumatic drug (DMARD) monitoring between November 2019 and July 2022, broken down by age‐band. The baseline period before lockdown is shown as an orange dashed vertical line. The monitoring window, measured as 3 months from the onset of the March 2020 COVID‐19 lockdown, is shown as a green dashed vertical line.
FIGURE 5
FIGURE 5
Proportions of patients overdue disease‐modifying antirheumatic drug (DMARD) monitoring between November 2019 and July 2022, broken down by sex. The baseline period before lockdown is shown as an orange dashed vertical line. The monitoring window, measured as 3 months from the onset of the March 2020 COVID‐19 lockdown, is shown as a green dashed vertical line.
FIGURE 6
FIGURE 6
Proportions of patients overdue disease‐modifying antirheumatic drug (DMARD) monitoring between November 2019 and July 2022, broken down by region. The baseline period before lockdown is shown as an orange dashed vertical line. The monitoring window, measured as 3 months from the onset of the March 2020 COVID‐19 lockdown, is shown as a green dashed vertical line.
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