Intravenous immune globulin-related hemolysis: comparing two different methods for case assessment.

BACKGROUND: Hemolysis is a rare adverse event associated with the use of intravenous immune globulin (IVIG). Using the Canadian experience, this article compares two methods used for case ascertainment of hemolysis after IVIG. STUDY DESIGN AND METHODS: This is a retrospective, descriptive analysis of case reports of hemolytic reaction after exposure to IVIG. The cases were ascertained from the Canada Vigilance database using the standardized MedDRA query for hemolytic disorders between the years 2006 and 2012 inclusively. The presence of a causal relationship was determined by using the Transfusion Transmitted Injuries Surveillance System (TTISS) algorithm. Cases were then reviewed against the standardized case definition of IVIG-associated hemolysis proposed by the IVIG Hemolysis Pharmacovigilance Group. RESULTS: A total of 942 adverse event reports after exposure to IVIG had been received by Canada Vigilance during the study period. A search for the adverse event of hemolytic disorder retrieved 313 reports (33%). Using a modified TTISS definition of hemolysis and the TTISS causality assessment algorithm, 226 cases were found to be at least possibly related to administration of IVIG, whereas 69 cases met the definition of the IVIG Hemolysis Pharmacovigilance Group. The amount of IVIG distributed increased over the study period; this trend was not reflected in the number of adverse reaction reports for "hemolytic disorder" received. CONCLUSION: The number of case reports per year received for the adverse event "hemolytic disorder" after exposure to IVIG fluctuated. The number of confirmed case reports varied depending on the case definition being used.

Monoclonal antibodies and progressive multifocal leukoencephalopathy.

Monoclonal antibodies have become an important treatment option for a number of serious conditions. Concerns have arisen about the potential association of these products with progressive multifocal leukoencephalopathy (PML). A list of monoclonal antibodies authorized for sale was derived from the Health Canada Drug Product Database. Case reports of PML after exposure to a monoclonal antibody authorized for use in Canada were retrieved by searching Canada Vigilance and WHO adverse event databases and through a Pub MED/Medline literature search. 182 adverse event case reports were retrieved (adalimumab -1 case, alemtuzumab-14, bevacizumab -3, cetuximab -1, efalizumab - 8, ibritumomab tiuxetan-5, infliximab-4, natalizumab-32, and rituximab-114). The Canadian Product Monographs for natalizumab and ritiximab contain box warnings for PML. A natalizumab registry has been established.