Intravenous immunoglobulin and the current risk of moderate and severe anaphylactic events, a cohort study

• Published in: Clinical and experimental immunology Vol. 206; no. 3; pp. 384 - 394
• Main Authors: Martinez, Carlos, Wallenhorst, Christopher, Nunen, Sheryl
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-12-2021; John Wiley and Sons Inc
• Subjects: Adrenergic Agonists - therapeutic use; Anaphylaxis; Anaphylaxis - drug therapy; Anaphylaxis - epidemiology; Cohort analysis; Epinephrine; Epinephrine - therapeutic use; Female; Humans; Immunoglobulin G - adverse effects; Immunoglobulin G - therapeutic use; Immunoglobulins; Immunoglobulins, Intravenous - adverse effects; Immunoglobulins, Intravenous - therapeutic use; Incidence; incidence rate; Intravenous administration; intravenous immunoglobulins; Male; Middle Aged; Original; Patients; predictors; Premier Healthcare Database; Retrospective Studies; Risk; Urticaria - epidemiology; predictors; Premier Healthcare Database; anaphylaxis; intravenous immunoglobulins; incidence rate
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13665

This large cohort study from the US Premier Healthcare Database evaluated the risk and predictors of anaphylaxis in association with intravenous immunoglobulin (IvIg) therapy in the inpatient and outpatient setting. Data were collected retrospectively (January 2009–December 2018) from 24 919 patients administered IgPro10 IvIg, median age 54 years. Immunoglobulins of interest were IgPro10 and other IvIg given before or after IgPro10. Moderate and severe anaphylaxis was identified from same‐day parenteral epinephrine and IvIg use and reviews of patient record summaries. Predictors for first anaphylactic reactions associated with IvIg administration were derived from adjusted incidence rate ratios (IRR) using Poisson regression. Moderate anaphylaxis in IvIg use was rare and severe anaphylaxis very rare based on a total of 124 moderate and four non‐fatal severe first anaphylactic events, incidence rate of 7.11 and 0.23/10 000 IvIg administrations, respectively. Age under 18 years was an independent predictor of moderate or severe anaphylactic events [adjusted incidence rate ratio = 2.94, 0.95 confidence interval  = 1.91–4.52] compared with those aged 18 years and older. First IvIg administration was a strong predictor of anaphylaxis. The IRR in those with a subsequent IvIg administration in the preceding 42 days decreased to 0.27 (0.17–0.42) and in those effectively IvIg‐naive (no IvIg for > 42 days) to 0.76 (0.44–1.32) compared with first IvIg use. The key conclusions from this study are that the risk of anaphylaxis has progressively reduced over the last decade, from 14.87 of 10 000 in 2009–10 to 4.39 of 10 000 IvIg administrations in 2017–18 and is rare overall, and that the risk of anaphylaxis is increased in those aged under 18 years.
This observational cohort study of 24,919 patients with a total of 175,535 administrations of intravenous immunoglobulin (IvIg) in a hospital setting shows a substantial reduction in the risk of moderate and severe anaphylaxis over a decade and establishes that anaphylaxis is rare overall. The risk of anaphylaxis has progressively reduced from 14.9/10,000 in 2009‐2010 to 4.4/10,000 IvIg administrations in 2017‐2018. Strong independent predictors of anaphylaxis were age under 18 and first dose of IvIg, and neither the IvIg dose nor the indication for its use was associated with the risk of anaphylaxis.