IVIg-exposure and thromboembolic event risk: findings from the UK Biobank

Abstract

BackgroundArterial 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.MethodsWe 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. Findings14 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.InterpretationIntravenous 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.

Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study

“…In the ProDERM study, patients with known history of TEE were excluded; however, results from the overall analysis showed that patients with certain risk factors for TEEs were more likely to experience TEEs than those without. Similarly, a study of data from the UK Biobank from 502,492 individuals on IVIg found that the rate of TEEs was threefold higher in patients with a history of TEE than those without [ 35 ].…”

Advances in diagnosis and management of distal sensory polyneuropathies

“…Taken together, these studies seem to suggest that intravenous Ig is effective in DSP when dysimmunity is present, and ineffective if those patients are excluded; although, more head-to-head trials are needed to definitively address this contention, particularly given the recent negative randomised controlled trial. Given the high cost of intravenous Ig, logistic difficulties and rare adverse thrombotic events,117 a high priority is to determine which patient populations should be eligible. Early-onset small fibre neuropathy in children and young adults requires difficult decisions given that up to 90% of cases appear to have dysimmune/inflammatory contributors,118 and potential life-long consequences of non-treatment.…”

Biological Therapies in Inflammatory Myopathies

“…In terms of safety, in addition to the well-known adverse effects of IVIg, including nausea, headaches, and fever, venous thromboembolism (VTE) is of particular concern since both IVIg treatment and inflammatory myopathy may increase the risk for VTE. 13 – 16 In the ProDERM trial, six patients treated with IVIg experienced eight thromboembolic events (an incidence of 1.54 occurrences per 100 patient-months). This observation led to a protocol change in IVIg infusion rate in order to minimize thromboembolic incidence.…”