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. 2024 Nov 19;4(1):238.
doi: 10.1038/s43856-024-00664-y.

Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform

Ruth E Costello  1 , Karen M J Waller  2   3   4 , Rachel Smith  5 , George F Mells  5   6 , Angel Y S Wong  7 , Anna Schultze  7 , Viyaasan Mahalingasivam  7 , Emily Herrett  7 , Bang Zheng  7 , Liang-Yu Lin  7 , Brian MacKenna  8 , Amir Mehrkar  8 , Sebastian C J Bacon  8 , Ben Goldacre  8 , Laurie A Tomlinson  7 , John Tazare  7 , Christopher T Rentsch  7   9 ; OpenSAFELY collaborative; LH&W NCS (or CONVALESCENCE) Collaborative
Affiliations

Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform

Ruth E Costello et al. Commun Med (Lond). .

Abstract

Background: Biological evidence suggests ursodeoxycholic acid (UDCA)-a common treatment of cholestatic liver disease-may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).

Methods: With the approval of NHS England, we conducted a population-based cohort study using primary care records between 1 March 2020 and 31 December 2022, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-varying UDCA exposure and COVID-19 related hospitalisation or death, stratified by geographical region and considering models unadjusted and fully adjusted for pre-specified confounders.

Results: We identify 11,305 eligible individuals, 640 were hospitalised or died with COVID-19 during follow-up, 400 (63%) events among UDCA users. After confounder adjustment, UDCA is associated with a 21% relative reduction in the hazard of COVID-19 hospitalisation or death (HR 0.79, 95% CI 0.67-0.93), consistent with an absolute risk reduction of 1.35% (95% CI 1.07%-1.69%).

Conclusions: We found evidence that UDCA is associated with a lower hazard of COVID-19 related hospitalisation and death, support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.

Plain language summary

Ursodeoxycholic acid is a drug used to treat liver disease. It has been proposed that it may prevent severe COVID-19 outcomes, however previous studies of this have had inconsistent results. We used electronic health records from people in the UK and identified people with two liver diseases: primary biliary cholangitis and primary sclerosing cholangitis. We looked at differences in hospitalisation and death between people taking UDCA and people who were not taking it. We found UDCA reduced the risk of severe COVID-19 outcomes by one-fifth. This suggests UDCA may help prevent serious COVID-19. Further clinical studies of UCDA should be undertaken, particularly in other groups with high risk or hospitalisation and death from COVID.

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Conflict of interest statement

Competing interests B.G. has received research funding from the Bennett Foundation, the Laura and John Arnold Foundation, the NHS National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, NHS England, 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 MRC, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he is a Non-Executive Director at NHS Digital; he also receives personal income from speaking and writing for lay audiences on the misuse of science. BMK is also employed by NHS England working on medicines policy and clinical lead for primary care medicines data. A.M. is a member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group, and received consulting fee from Induction Healthcare. L.A.T. has received research funding from MRC, Wellcome, NIHR and GSK, consulted for Bayer in relation to an observational study of chronic kidney disease (unpaid), and is a member of 4 non-industry funded (NIHR/MRC) trial advisory committees (unpaid) and MHRA Expert advisory group (Women’s Health). R.E.C. has shares in AstraZeneca. V.M. received a grant from NIHR. A.S. is employed by LSHTM on a fellowship sponsored by GSK. J.T. received an AstraZeneca grant for unrelated COVID-19 research. G.F.M. and R.S. have received research funding from Intercept Pharmaceuticals and Advanz Pharma. All other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Study design.
Fig. 2
Fig. 2. Forest plot of hazard ratio and 95% confidence intervals for UDCA vs no UDCA for each outcome in the main analysis and sensitivity analyses (n = 11,305).
Death alone outcome for PSC only sensitivity analysis not available due to small number of deaths.
Fig. 3
Fig. 3. Standardised cumulative incidence curves.
The panels show standardised cumulative incidence curves for (a) composite outcome of COVID-19 hospitalisation or death, (b) COVID-19 death only, (c) COVID-19 hospitalisation only. The red line refers to the cumulative incidence estimate for the no UDCA group, the dashed blue line refers to the cumulative incidence estimate for the UDCA group. Shaded areas refer to the 95% confidence interval of the cumulative incidence.
See this image and copyright information in PMC

References

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