Mild IVIG-Related Adverse Events Are Frequent in Children, With Serious Reactions Possible

Results from a recent retrospective cohort study published in Transfusion reveal that therapy with intravenous immunoglobulin (IVIG) in pediatric patients frequently causes mild adverse events (AEs), with severe reactions also possible, emphasizing the need for prospective studies to confirm risk factors for AEs.¹

Intravenous immunoglobulin infusions can cause mild adverse events, with the rarer possibility of life-threatening reactions. | Image Credit: © Sherry Young | stock.adobe.com

IVIG has been shown in multiple case studies and clinical trials to be effective in an increasing number of inflammatory and autoimmune disorders. These include pediatrics with multisystem inflammatory syndrome and those with immune thrombocytopenia.^2-4

Despite the effectiveness of the therapy, IVIG can still cause AEs following administration. Oftentimes, these reactions are self-limited and of mild-to-moderate severity; they include fever, chills, headache, myalgia, and fatigue, among others. Other, more serious AEs include acute renal failure, thromboembolic events, meningitis, and transfusion-related acute lung injury (TRALI).¹

The investigators sought to examine the incidence and risk factors of IVIG-related AEs in children as the expansion of its use increases, especially for off-label indications. In the trial, the incidence, severity, and risk for IVIG-related AEs in pediatric inpatients at a tertiary center in Quebec City, Canada were analyzed to produce a comprehensive assessment of both non-serious and serious AEs.¹

Serious AEs were considered those that demand significant medical attention or bear potentially life-threatening risks; serious AEs and AEs of grade 3 or higher were considered severe reactions, according to the investigators.¹

A total of 296 hospitalized children were administered IVIG during the study period, with 228 of them (77.1%) meeting the trial inclusion criteria. Importantly, 43 patients (18.9%) were administered 3 or more IVIG treatments during their stay in the hospital—which could increase the risk of AEs—whereas most patients (122, 53.5%) only received 1 infusion.¹

Throughout the duration of the trial, 213 IVIG-related AEs were documented, occurring in 125 out of 478 IVIG perfusions (26.2%; 95% CI, 22%-30%) and impacting 89 patients (39.0%; 95% CI, 33%-46%). The most common IVIG-related AEs were fever (13.6%; 65/478), headache (6.7%; 32/478), and tachycardia (6.5%; 31/478). IVIG-related AEs that occurred immediately were observed more frequently than delayed IVIG AEs (58.2%, 124/213 versus 32.4%, 69/213), according to the investigators.¹

Most observed AEs were of mild severity and did not require additional treatment (56.8%; 121/213). Contrastingly, 11.3% (24/213) of AEs were graded 3 or higher, while 7.0% (15/213) were classified as serious; altogether, 16.0% (34/213) of all AEs were classified as severe reactions. In some cases, dedicated treatment for IVIG-AEs were administered, including acetaminophen or antihistamines.¹

Factors associated with the development of IVIG-AEs were also analyzed. The investigators found a significantly higher rate of AEs in patients aged between 1 to 9 years and 10 to 17 years, compared with patients aged under 1 year. Additionally, patients with documented concomitant allergies, regardless of whether the allergies were to antibiotics or other medications, had a much higher rate of IVIG-AEs, with no other comorbidities demonstrating a significant difference.¹

Interestingly, IVIG infusions that were intended to treat inflammatory conditions were found to have significantly higher IVIG-AE rates compared with those administered for replacement therapy. Patient dehydration was also associated with a significantly higher occurrence of AEs, although IV hydration did not reduce IVIG-AE rate. A multivariable analysis confirmed that AEs displayed significant associations with older age and increased doses of IVIG.¹

The investigators discussed the prospect of this trial being the first to identify inflammatory indications as a predisposing factor for pediatric IVIG-AEs. Immediate IVIG-AEs are thought to be inflammatory responses triggered by the preparation of IVIG, which could explain why inflammatory states predispose patients to these reactions. Higher doses are also often necessary for inflammatory conditions, which is a known risk factor for IVIG-AEs.^1,2

“Recognizing the prevalence of IVIG-AEs and their potential contributing factors is essential for enhancing the care of children receiving IVIG,” the study authors concluded.¹

REFERENCES

1. Côté J, Chaloult-Lavoie M, Poulin É, et al. Incidence of adverse events related to intravenous immunoglobulin therapy in children. Transfusion. 2024. doi:10.1111/trf.18083

2. Halpern L. Lower dose of IVIG remains effective in treating pediatric immune thrombocytopenia compared with higher dose. Pharmacy Times. Published October 3, 2024. Accessed December 23, 2024. https://www.pharmacytimes.com/view/lower-dose-of-ivig-remains-effective-in-treating-pediatric-immune-thrombocytopenia-compared-with-higher-dose

3. Antrim A. Case studies show IVIG may improve neurological symptoms in pediatric multisystem inflammatory syndrome. Pharmacy Times. Published August 23, 2023. Accessed December 23, 2024. https://www.pharmacytimes.com/view/case-studies-show-ivig-may-improve-neurological-symptoms-in-pediatric-multisystem-inflammatory-syndrome

4. Halpern L. Favorable outcomes possible with IVIG treatment for multisystem inflammatory syndrome in children. Pharmacy Times. Published September 23, 2024. Accessed December 23, 2024. https://www.pharmacytimes.com/view/favorable-outcomes-possible-with-ivig-treatment-for-multisystem-inflammatory-syndrome-in-children