The “risky” business of thromboembolic events for patients with intravenous immunoglobulin treatment

Dr Mahima Kapoor is the first author on a study which shows higher
risk for patients who have suffered clotting events from a particular
treatment, intravenous immunoglobulin.

by Dr Loretta Piccenna, Department of Neuroscience

An important analysis using the UK Biobank published this month by researchers in the Neuromuscular group in the Department of Neuroscience has shown a three-fold higher risk of blood clots, or thromboembolic events (TEEs), in patients with a prior history of these events when they were treated with intravenous immunoglobulin (IVIg) (1).

First author of the study, Dr Mahima Kapoor, led the largest ever population study (over 500,000 community-based cohort) done worldwide which was a collaboration between the Department of Neuroscience at Monash University, the Department of Neurology, the Alfred Hospital, the Centre for Neuromuscular Diseases at UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery (NHNN) in London, UK. 

The team developed risk prediction models using patient-reported and health-linkage data from the UK Biobank to find out the association.

The findings confirm those reported from a review of pooled randomised clinical trials, but differ from other studies which also had large cohorts, but which didn’t specifically take into account cardiovascular risk factors in relation to IVIg. A previous retrospective study from this group showed a seven-fold increase in incidence of TEEs in NHNN’s neuromuscular cohort treated with IVIg compared with population-based rates (2).  

Thromboembolic events, or TEEs, are a rare but serious complication. The US Food and Drug Authority has a "black-box" warning on the risk of TEEs and the European Medicines Agency also cautions against the dosing to reduce the risk of TEEs. TEEs include fatal or non-fatal myocardial infarction (heart attack), stroke, deep vein thrombosis, pulmonary embolism, acute ischaemic heart disease, portal vein thrombosis and others.

The Neuromuscular clinic at the Alfred manages many patients who are on maintenance intravenous immunoglobulin (IVIg) treatment for CIDP and multifocal motor neuropathy. Dr Kapoor said, “the findings are really important for clinical practice so that clinicians are aware of the cardiovascular risk when prescribing intravenous immunoglobulin treatment.
 
Local secondary prevention guidelines, e.g. obtaining a complete medical history, and ensuring patients are on the appropriate secondary prevention medications, should be closely implemented and reinforced in patients who have had a prior history of TEEs."

Recently, having her PhD conferred, Dr Mahima Kapoor presented the findings at the annual Australian and New Zealand Association of Neurologists, receiving the Jim Lance Young Investigator Award for Best Platform Presentation.
 
She is now the Head of the Neuromuscular service at Alfred Health, and is leading the creation of the expanded Neuromuscular clinic at Sandringham. She is working on setting up a number of neuromuscular research projects and clinical trials, including leading the Australian arm of the international INCBase, and building ties with haematology and neurogenetics.

 
Acknowledgements
 
This research was conducted with the UK Biobank resource, under application 45291 and 43383. UK Biobank was established by the Wellcome Trust, Medical Research Council, Department of Health, Scottish Government, and Northwest Regional Development Agency. UK Biobank has also had funding from the Welsh Assembly Government and the British Heart Foundation. Data collection was funded by UK Biobank.

References 

1. Kapoor M, Hunt I, Spillane J, Bonnett LJ, Hutton EJ, McFadyen J, Westwood JP, Lunn MP, Carr AS, Reilly MM. IVIg-exposure and thromboembolic event risk: findings from the UK Biobank. J Neurol Neurosurg Psychiatry. 2022 Jun 10:jnnp-2022-328881. doi: https://doi.org/10.1136/jnnp-2022-328881

2. Kapoor M, Spillane J, Englezou C, et al. Thromboembolic risk with IVIg: Incidence and risk factors in patients with inflammatory neuropathy. Neurology 2020;94(6):e635-e38. doi: https://doi.org/10.1212/wnl.0000000000008742