title: Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta-analysis of RCTs.
abstract: Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIg's therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg-treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg-treated patients compared with control patients (odds ratio = 1.10, 95% CI: 0.44, 2.88; risk difference = 0.0%, 95% CI: -0.7%, 0.7%, I(2)  = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE. Am. J. Hematol. 91:594-605, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Ammann
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Cole B
authors.initials: CB
authors.lastname: Haskins
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Fillman
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Ritter
authors.affiliation: Hardin Library for the Health Sciences, University of Iowa, Iowa City, Iowa.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Gu
authors.affiliation: Office of Biostatistics and Epidemiology, Center for Biologics Evaluation & Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Winiecki
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Carnahan
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: James C
authors.initials: JC
authors.lastname: Torner
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Fireman
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jones
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Chrischilles
mesh_terms: D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000139:chemically induced* / Q000209:etiology
chemical_list: D016756:Immunoglobulins, Intravenous