Second Dose of IVIG in Guillain-Barré Syndrome Increases Adverse Events Without Major Clinical Benefit

A second dose of intravenous immunoglobulin (IVIG) following a first dose in patients with Guillain-Barré syndrome (GBS) was found to increase serum immunoglobulin G (IgG) levels but without improvement in clinical outcomes and a corresponding heightened risk of serious adverse events (AEs), according to study results published by investigators in Annals of Clinical and Translational Neurology.¹

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IVIG is a proven treatment for GBS and has been found to be effective in multiple clinical trials. One landmark trial, conducted by Hughes et al, found that IVIG initiated within 2 weeks from the onset of disease could hasten recovery as much as plasma exchange therapy, with IVIG being significantly more likely to be completed fully. Still, approximately 20% of patients progress throughout IVIG treatment, necessitating more effective treatment regimens.^1,2

Administering a second dose of IVIG has been investigated, with study authors in the pivotal phase 3 SID-GBS trial finding no therapeutic value to repeat IVIG dosing in patients with GBS and a poor prognosis, noting that a second dose should not be considered due to such a prognosis. Still, many patients with GBS who receive IVIG receive repeat IVIG dosing anyway; one study found that 39.7% of a cohort of patients with GBS had repeat IVIG dosing, with most of that percentage receiving 3 or more doses.^3,4

Given the continued presence of repeat IVIG dosing and the variable clinical responses that are associated with IVIG treatment, the investigators of the current study sought to elucidate the pharmacokinetics and pharmacodynamic (PK/PD) impacts of a second IVIG dose (SID) on serum IgG concentration and clinical outcomes in patients with GBS. The investigators aimed to analyze the dose-response relationship with IVIG administration and examine characteristics of patients that could benefit from an altered dosing strategy.¹

Investigators utilized the patient population of the SID-GBS trial in their analysis. Patient evaluation was conducted at baseline and at 1, 2, 4, 8, 12, and 26 weeks following the beginning of the first course of IVIG. Assessments used to measure patient performance included the GBS disability score (GBS-DS) and the Medical Research Council sum score (MRC-SS).¹

A total of 238 patients from the SID-GBS cohort were included in the final analysis; of these, 160 patients reported a positive prognosis following the first course of IVIG and were not randomized for a subsequent dose. Out of the remaining 78 patients with a poor prognosis, 44 were randomized to receive SID and 34 received placebo 1 week following the first IVIG course. When analyzing serum IgG levels, investigators observed elevated concentrations following a SID for at least 3 weeks compared with patients who received placebo or those who were not randomized.¹

Regarding clinical outcomes, the investigators found no clear association between the clinical outcome and the area under the curve (AUC) of IgG between 0 and in weeks in the SID group. Correspondingly, after stratifying for the lowest 50% exposure in the SID group, a second course of IVIG was observed to be unbeneficial compared with patients in the placebo group with similar low exposure levels.¹

Perhaps most critically, serious AEs were more prevalent in patients receiving SID. Across the total of 33 patients that experienced serious AEs in the study cohort, 12 (47.7%) occurred in the single IVIG course group, while 21 (47.7%) occurred in the SID group. Furthering this point, investigators found that, in patients with 1 or more serious AEs following IVIG treatment, there was generally lower IgG exposure during the 0-to-2-week period compared with patients who did not experience any serious AEs.¹

“We observed no benefit from administering a second dose of IVIG in cases of severe GBS,” the study authors concluded. “Model-informed precision dosing, tailored to individual patient characteristics, has the potential to optimize and personalize IVIg therapy in inflammatory neuropathies, but more biomarkers are needed.”¹

REFERENCES

1. Tilburg SJV, Huizinga R, Kuitwaard K, et al. If it does not help, it might hurt: Pharmacodynamics of a second IVIG course in Guillain-Barre syndrome. Annals Clin Translat Neurol. 2025. doi:10.1002/acn3.52313

2. Antrim A. Study: Intravenous immunoglobulin hastens recovery of early onset Guillain-Barre. Pharmacy Times. Published March 24, 2021. Accessed March 18, 2025. https://www.pharmacytimes.com/view/study-intravenous-immunoglobulin-hastens-recovery-of-early-onset-guillain-barre

3. Walgaard C, Jacobs BC, Lingsma HF, et al. Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS): A double-blind, randomized, placebo-controlled trial. The Lancet Neurology. 2021;20(4):275-283. doi:101016/S1474-4422(20)30494-4

4. Halpern L. Repeat IVIG dosing common in Guillain-Barre syndrome, suggesting harm in non-responders. Pharmacy Times. Published October 18, 2024. Accessed March 18, 2025. https://www.pharmacytimes.com/view/repeat-ivig-dosing-common-in-guillain-barr-syndrome-suggesting-harm-in-non-responders