Meta-Analysis Reveals No Evidence that IVIG Administration Increases Risk of Thromboembolic Events

Analysis of 31 randomized controlled trials (RCTs) published between 1995 and 2015 found no evidence of increased thromboembolic event (TEE) risk among patients treated with intravenous immune globulin (IVIG) compared to control patients, according to a report by a team of investigators that included epidemiologists at the U.S. Food and Drug Administration (FDA).

Of a total of 4,129 participants (2,318 IVIG-treated, 1,811 control) who were eligible for quantitative synthesis, no significant difference was found in TEE risk (odds ratio = 1.10, 95% confidence interval [CI]: 0.44, 2.88; risk difference = 0.0%, 95% CI: -0.7%, 0.7%, I2 = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints.

These findings are at odds with prior case reports and observational studies indicating that IVIG may cause TEEs, leading the FDA to require a boxed warning in 2013. The investigators acknowledged, however, that “trial publications provided little specific information concerning the methods used to ascertain potential adverse events.” They added that “care should be taken in extrapolating our results to patients with higher baseline risks of TEE.”