P4A156: Incidence and Risk Factors of Adverse Events Related to Intravenous Immunoglobulins Therapy in Children from 2016 to 2020

Background: Intravenous immunoglobulins (IVIG) therapy are increasingly used in the treatment of various pediatric diseases. Unfortunately, data about frequency and underlying mechanisms of IVIG-related adverse events (IVIG-AEs) in children are limited. Objectives of this study were to document the incidence of IVIG-AEs in pediatric hospitalized patients and to identify risk factors for IVIG-AEs.

Methods: In this retrospective cohort study, patients aged < 18 years old who received IVIG therapy for any indication as inpatients at a Canadian pediatric tertiary care center between 2016 and 2020 were included. Patients and IVIG-perfusions characteristics were collected, as well as any IVIG-AEs occurring during the perfusion or up to 10 days after. IVIG-AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Bivariate and multivariate logistic regressions were used to explore the associations between the variables and the incidence of IVIG-AEs: results are presented as odd ratios (OR) with confidence level of 95%.

Results: We included 228 children in this study (mean age: 4 years, standard deviation: 4.54), totaling 478 IVIG perfusions. Indications included treatment for inflammatory (120/228, 52.6%) and autoimmune (81/228, 35.5%) disorders, as well as replacement for immunodeficiency (27/228, 11.8%). A total of 213 IVIG-AEs were reported in 89/228 (39%) of patients, and 125/478 (26.2%) of perfusions. Fever (65/478, 13.6%) was the most frequent IVIG-AE, followed by headache (32/478, 6.7%) and tachycardia (31/478, 6.5%). Most IVIG-AEs were of mild (57%) or moderate (31%) severity, but 12% were severe reactions (serious IVIG-AEs or grade 3-4). The highest proportion of IVIG-AEs occurred when administered for inflammatory conditions (33.8%) vs auto-immune (22.2%) or replacement (14.9%) Older children of 1-9 years and 10-17 years were more at risk of developing IVIG-AEs than children of < 1 year (OR 3.29 [CI: 1.61-6.76] and OR 8.26 [CI: 3.25 -21.3] respectively), as each year of age increased the risk of IVIG-AE by 14% (p < 0.0001). The following factors were predictive of IVIG-AEs: dehydration (OR 2.55 [CI: 1.43-4.55]), concurrent allergies (OR 2.87 [CI: 1.26-6.56]), first perfusion (OR 1.53 [CI: 1.02-2.30]), and higher dosage (OR 2.14 [CI: 1.39-3.33]). Conversely, co-administration of steroid significantly decreased the risk of IVIG-AEs (OR 0.44 [CI: 0.22-0.86]) (p < 0.05 in all cases).

Conclusion: IVIG-AEs are frequent in children. While most of them are self-limited, more serious complications may occur. Prospective studies are necessary to evaluate if adequate hydration, low concentrations of IVIG products and the administration of glucocorticoid prior to the perfusion could minimize these IVIG-AEs, especially in high-risk children.