IVIG Demonstrates Improved Response Rates in Autoimmune Encephalitis Trial

A phase 3 randomized study presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18-22 in Chicago, Illinois, showed that intravenous immunoglobulin (IVIG) improved clinical response rates in patients with autoimmune encephalitis (AE) who had inadequate response to steroid pulse therapy.¹

Autoimmune encephalitis represents a heterogeneous group of immune-mediated disorders characterized by subacute cognitive dysfunction, seizures, psychiatric symptoms, and neurologic decline. Although first-line treatment typically includes corticosteroids, IVIG, or plasma exchange, the evidence base supporting IVIG—particularly from controlled trials—has remained limited.²

In this double-blind, active-controlled study (NCT05177939), investigators led by Ko Sakamoto, MD, of Takeda Pharmaceutical Company, enrolled 40 patients with AE who failed to respond adequately to steroid pulse therapy.¹ Participants were randomized 1:1 to receive either IVIG (NPB-01) or continued steroid pulse therapy, with the primary endpoint defined as a ≥40% improvement on the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) at Week 4.¹

Among patients with cell-surface antigen antibodies—the primary analysis population—response rates were 57.1% in the IVIG group compared with 0% in the control group.¹ In the broader full analysis set (n=20 per group), response rates were 50.0% with IVIG versus 25.0% with continued steroid therapy.¹ Secondary outcomes, including changes in modified Rankin Scale (mRS) scores, were consistent with the primary findings and supported improved functional outcomes in the IVIG-treated cohort.¹

Safety findings were comparable between groups, with most adverse events reported as mild to moderate in severity.¹ These results suggest that IVIG may offer a clinically meaningful benefit in patients with AE who do not respond to corticosteroids alone, a population in which treatment decisions are often guided by limited prospective data.

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IVIG is a pooled immunoglobulin therapy derived from donor plasma and is widely used across neurologic disorders, including chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and myasthenia gravis.³ Its mechanism is multifactorial, involving modulation of autoantibodies, complement inhibition, and effects on Fc receptor signaling.³ However, much of the evidence supporting IVIG use in AE has historically come from retrospective series or small prospective studies.

For example, a 2022 prospective, open-label study published in Annals of Clinical and Translational Neurology demonstrated that IVIG treatment led to significant improvements in mRS scores as early as day 8, with continued benefit through day 29.² In that study, 6 of 18 patients achieved favorable outcomes with IVIG alone, although many required rescue immunotherapy, highlighting the complexity of treatment in AE.²

The current phase 3 study builds on this earlier work by introducing a controlled design and evaluating NPB-01, an investigational IVIG formulation designed to optimize immunomodulatory effects. Unlike conventional IVIG, next-generation products such as NPB-01 aim to enhance anti-inflammatory activity, improve consistency, and potentially reduce treatment burden through more efficient Fc-mediated immune modulation.

From a clinical standpoint, the findings presented at AAN 2026 provide important context for treatment escalation in AE. Patients who fail first-line corticosteroids often require rapid transition to second-line therapies, including IVIG, plasma exchange, or B-cell–depleting agents. The demonstrated response rates in this trial suggest that IVIG, including newer formulations, may play a more clearly defined role in this treatment pathway, particularly in antibody-mediated disease.

Despite these promising findings, several limitations remain, including the relatively small sample size and heterogeneity of AE subtypes included in the study.¹ Larger confirmatory trials and longer-term follow-up will be necessary to better define durability of response, optimal sequencing strategies, and comparative effectiveness against other immunotherapies.

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REFERENCES
1. Sakamoto K, et al. Phase 3 clinical study of IVIG for efficacy and safety in autoimmune encephalitis. Presented at: American Academy of Neurology Annual Meeting; April 18–22, 2026; Chicago, IL.
2. Lee ST, Lee HS, Lee WJ, et al. The safety and efficacy of intravenous immunoglobulin in autoimmune encephalitis. Ann Clin Transl Neurol. 2022;9(5):e51540. doi:10.1002/acn3.51540
3. Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291(19):2367-2375. doi:10.1001/jama.291.19.2367