Science News: Study Examines Thromboembolic Risk With IVIg and SCIg in Neuroinflammatory Disease

Submitted by: Ben Becker, MD

Edited by: Rebecca O'Bryan, MD

Citation: Rogers T, White LM, Cooper S, Smith H, Gosal D, Keh RYS. Thromboembolic risk of intravenous and subcutaneous immunoglobulin treatment for neuroinflammatory diseases. J Neurol Neurosurg Psychiatry. 2026 Feb 13;97(3):204-208. doi: 10.1136/jnnp-2025-337097. PMID: 41115784.

Intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) are established therapies neuroinflammatory conditions such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN), and are also used in other neuromuscular disorders including myasthenia gravis. While IVIg is known to increase the risk of thromboembolic events (TEEs), the comparative risk associated with SCIg has been less well defined. This single‑center retrospective cohort study examined TEE incidence in patients receiving IVIg or SCIg and evaluated the utility of the QRISK3 cardiovascular risk algorithm in predicting TEE occurrence.

The study included 243 patients treated at the Manchester Centre for Clinical Neurosciences over 15 years, yielding 1,401 patient‑years of treatment information. Patients receiving SCIg had significantly higher QRISK3 scores, reflecting older age and a greater burden of vascular risk factors. TEEs occurred more frequently in the IVIg cohort (n=14) than in the SCIg cohort (n=2), corresponding to incidence rates of 1.38 and 0.52 events per 100 patient‑years, respectively, though this difference did not reach statistical significance. Among IVIg‑treated patients, those on anticoagulant or antiplatelet therapy were more likely to experience TEEs, likely reflecting higher baseline vascular risk combined with IVIg’s independent pro‑thrombotic effect. This pattern was not observed in the SCIg group.

The study also assessed QRISK3 as a risk‑stratification tool. A threshold of 12.2% identified both SCIg‑associated TEEs and 10 of 14 IVIg‑associated TEEs (sensitivity 75%, specificity 61%), but the positive predictive value remained low (9%) given the rarity of events.

The evidence base for thromboembolic risk in neuroinflammatory patients treated with IVIg has been limited, making this study, now the largest cohort in both patient number and patient‑years, the most substantial evaluation of this question to date. Despite the SCIg cohort having higher baseline vascular risk, SCIg was no more likely than IVIg to be associated with TEEs. Although there was a numerical trend toward fewer TEEs with SCIg, the rarity of events limited statistical significance. The higher baseline risk in the SCIg group reflects local practice, where SCIg is preferentially used in patients with elevated vascular risk.

Importantly, all TEEs occurring in patients on antiplatelet or anticoagulant therapy were observed in the IVIg cohort, supporting the possibility that IVIg itself may act as an independent TEE risk factor. Likewise, TEE events in individuals under age 60 occurred exclusively during IVIg treatment.

QRISK3 scores correlated with several TEE‑related outcomes, but identifying a clinically meaningful cut‑off proved challenging due to the low positive predictive value, likely a consequence of the overall rarity of TEEs in immunoglobulin‑treated populations.

This is the biggest cohort to date of risk of TEE in neuromuscular conditions. This data also generally supports the clinical equipoise to treat those at high risk of TEE preferably with SCIg.