Thromboembolic risk of intravenous and subcutaneous immunoglobulin treatment for neuroinflammatory diseases

Background Intravenous immunoglobulin (IVIg) is effective in many neuroinflammatory disorders but carries a risk of thromboembolic events (TEEs). Subcutaneous immunoglobulin (SCIg) is effective, but its thromboembolic risk profile is less well-described, particularly in patients with prominent vascular risk factors. We investigated the thromboembolic risk profile of IVIg and SCIg using a large single-centre retrospective dataset of patients with neuroinflammatory disorders. Methods 243 patients treated with immunoglobulin over a 15-year monitoring period were analysed. Demographic information was used to calculate QRISK3 vascular risk scores. Patients were grouped based on having received IVIg-only, SCIg-only or both IVIg and SCIg (with subgroup analysis of IVIg and SCIg treatment periods). TEE incidence rates were compared. The relationship between QRISK3 and TEE likelihood was analysed. Results A total of 1401 patient-years immunoglobulin treatment data were obtained. The SCIg-only cohort was older with higher QRISK3 scores. More patients on IVIg (n=14) than SCIg (n=2) experienced TEEs on treatment (1.38 vs 0.52 events per 100 patient-years), but this difference was not statistically significant. IVIg-treated patients with TEEs were younger (p=0.039) than SCIg-treated TEE patients. QRISK3 scores broadly correlated with thromboembolic risk across the cohort (p=0.027), but some younger IVIg patients with low QRISK3 scores experienced TEEs indicating that IVIg but not SCIg independently increases thromboembolic risk. QRISK3 scores >10% identified 71% and 100% of TEEs in IVIg-treated and SCIg-treated patients, respectively, but are insensitive (7%) as TEEs are rare events. Conclusions SCIg is at least equivalent in thromboembolic risk to IVIg and may be safer for patients with existing vascular risk factors.