Article Text

Download PDFPDF
Original research
IVIg-exposure and thromboembolic event risk: findings from the UK Biobank
  1. Mahima Kapoor1,2,
  2. Ian Hunt3,
  3. Jennifer Spillane4,5,
  4. Laura Jayne Bonnett6,
  5. Elspeth Jane Hutton7,8,
  6. James McFadyen9,10,
  7. John-Paul Westwood11,
  8. Michael P Lunn12,13,
  9. Aisling S Carr14,
  10. Mary M Reilly15
  1. 1MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
  2. 2Department of Neurosciences, Monash University Central Clinical School, Melbourne, Victoria, Australia
  3. 3Tasmanian Institute of Agriculture, University of Tasmania, Hobart, Tasmania, Australia
  4. 4Neurology, Royal Free Hospital Foundation Trust, London, UK
  5. 5MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery and UCL Queen Square Institute of Neurology, London, UK
  6. 6Biostatistics, University of Liverpool, Liverpool, UK
  7. 7Neurology, Alfred Health, Melbourne, Victoria, Australia
  8. 8Neuroscience, Monash University, Melbourne, Victoria, Australia
  9. 9Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
  10. 10Department of Clinical Hematology, The Alfred Hospital, Melbourne, Victoria, Australia
  11. 11Department of Haematology, University College London Hospital, London, UK
  12. 12MRC Centre for Neuromuscular Disease and Department of Molecular Neuroscience, University College London Hospitals NHS Foundation Trust National Hospital for Neurology and Neurosurgery, London, UK
  13. 13NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK
  14. 14MRC Centre for Neuromuscualr Diseases, National Hospital of Neurology and Neurosurgery, London, UK
  15. 15MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
  1. Correspondence to Dr Mahima Kapoor, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; mahima.kapoor{at}monash.edu

Abstract

Background Arterial and venous thromboembolic events (TEEs) have been associated with intravenous Ig use, but the risk has been poorly quantified. We aimed to calculate the risk of TEEs associated with exposure to intravenous Ig.

Methods We included participants from UK Biobank recruited over 3 years, data extracted September 2020.

The study endpoints were incidence of myocardial infarction, other acute ischaemic heart disease, stroke, pulmonary embolism and other venous embolism and thrombosis.

Predictors included known TEE risk factors: age, sex, hypertension, smoking status, type 2 diabetes mellitus, hypercholesterolaemia, cancer and past history of TEE. Intravenous Ig and six other predictors were added in the sensitivity analysis.

Information from participants was collected prospectively, while data from linked resources, including death, cancer, hospital admissions and primary care records were collected retrospectively and prospectively. 

Findings 14 794 of 502 492 individuals had an incident TEE during the study period. The rate of incident events was threefold higher in those with prior history of TEE (8 .7%) than those without previous history of TEE (3.0%).

In the prior TEE category, intravenous Ig exposure was independently associated with increased risk of incident TEE (OR=3.69 (95% CI 1.15 to 11.92), p=0.03) on multivariate analysis. The number needed to harm by exposure to intravenous Ig in those with a history of TEE was 5.8 (95% CI 2.3 to 88.3).

Intravenous Ig exposure did not increase risk of TEE in those with no previous history of TEE.

Interpretation Intravenous Ig is associated with increased risk of further TEE in individuals with prior history of an event with one further TEE for every six people exposed. In practice, this will influence how clinicians consent for and manage overall TEE risk on intravenous Ig exposure.

  • CARDIOLOGY
  • IMMUNOLOGY
  • NEUROPATHY
  • PHARMACOLOGY

Data availability statement

Data may be obtained from a third party and are not publicly available. Data from the UK Biobank project were obtained from a third party, UK Biobank, on application. Interested parties can apply for data from UK Biobank directly, at http://www.ukbiobank.ac.uk.

Statistics from Altmetric.com

Data availability statement

Data may be obtained from a third party and are not publicly available. Data from the UK Biobank project were obtained from a third party, UK Biobank, on application. Interested parties can apply for data from UK Biobank directly, at http://www.ukbiobank.ac.uk.

View Full Text

Footnotes

  • Contributors ASC, MPL and MMR designed the original hypothesis and MK ran all the analyses in collaboration with IH and LJB. MK wrote the first draft of the report, apart from the model performance section and corresponding figure, which was written by IH. All authors interpreted the results, revised the text and approved the final draft of the report. MMR is responsible for the overall content as the guarantor.

  • Funding MK gratefully received funding from a patient’s bequest, PhD scholarship from the Bethlehem Griffiths Research Foundation (BGRF1810-1) and an Australian Government Research Training Program (RTP) Scholarship. MPL, MMR and ASC are also supported by the National Institute for Health Research University College London Hospitals Biomedical Research. JDM is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1161499).

  • Competing interests MK reports Grifols sponsorship for attendance at meeting. ASC reports Grifols sponsorship for attendance at meeting and honorarium from CSL and Lupin for an advisory role. MPL was a Primary Investigator in studies for CSL Behring, UCB Pharma, Novartis, Octapharma. He has also received ad hoc consulting fees from CSL Behring, UCB and an honorarium from Terumo BCT. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.