BACKGROUND: Thrombotic events (TEs) are rare but often serious adverse events that could occur after administration of immune globulin (IG) products. Our study objective was to assess occurrence of recorded TEs after administration of different US‐licensed IG products and investigate potential risk factors using a large administrative database. STUDY DESIGN AND METHODS: This is a retrospective claims‐based cohort study of individuals exposed to IG products from January 1, 2008, through September 30, 2010, using HealthCore's Integrated Research Database, a longitudinal health care database. IG products were identified by recorded Healthcare Common Procedure Coding System codes. TEs were ascertained via International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for same‐day TEs by IG product, while controlling for confounders. RESULTS: Of 11,785 individuals exposed to IG products in the study period, 122 (1%) had TE(s) recorded on the same day as IG administration. TE rates per 1000 persons exposed ranged from 6.1 to 20.5 for different IG product groups. Vivaglobin users had an increased same‐day TE risk compared to reference Gammagard Liquid users (OR, 3.56; 95% CI, 1.54‐8.23). An increased TE risk was also found with older age (≥45 years), prior TE(s), and hypercoagulable state(s). CONCLUSION: The study suggests potentially elevated TE rates for different IG products, including subcutaneous. It also identifies important recipient TE risk factors and suggests that risk–benefit profiles should be weighed before IG administration. The observed differences may be due to various factors such as dosage, administration rates, and product manufacturing processes that warrant further evaluation.

Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims-based study assessed occurrence of same-day TEs following administration of HIGs during 2008-2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRD SM ) and laboratory testing of products' procoagulant Factor XIa activity by U.S. Food and Drug Administration. Multivariable regression was used to estimate same-day TE risk for different products. Of 101,956 individuals exposed to 23 different HIG product groups, 86 (0.84 per 1,000 persons) had a TE diagnosis code (DC) recorded on the same day as HIG administration. Unadjusted same-day TE DC rates (per 1,000 persons) ranged from 0.4 to 148.9 for different products. GamaSTAN S/D IG >10 cc had statistically significantly higher same-day TE DC risk compared to Tetanus IG (OR 5 57.57; 95% CI 5 19.72-168.10). Increased TE risk was also observed with older age ( 45 years), prior thrombotic events, and hypercoagulable state(s). Laboratory investigation identified elevated Factor XIa activity for GamaSTAN S/D, HepaGam B, HyperHep B S/D, WinRho SDF, HyperRHO S/D full dose, and HyperTET S/D. Our study, for the first time, identified increase in the same-day TE DC risk with GamaSTAN S/D IG >10 cc and suggests potentially elevated TE risk with other HIGs. Am.

We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic healthcare data. In a retrospective analysis, we showed that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable). During >5 years of monitoring, rate differences (RDs) comparing rosuvastatin to atorvastatin were -0.1 cases of rhabdomyolysis per 1,000 person-years (95% CI, -0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI, -6.0, 1.6). The RD for hepatotoxicity comparing telithromycin to azithromycin was 0.3 cases per 1,000 person-years (95% CI, -0.5, 1.0). In a setting in which false positivity is a major concern, the system did not generate alerts for three drug-outcome pairs.

Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies.