title: Is there evidence for recommending specific intravenous immunoglobulin formulations? A systematic review of head-to-head randomized controlled trials.
abstract: Intravenous immunoglobulins (IVIG) have been used for several licensed and off-label indications. Each IVIG product is a unique formulation of IgG and excipients, making them distinct products. How these differences impact on individual IVIG product efficacy and safety are not well established but can be investigated by head-to-head randomized controlled trials (RCT). A systematic review of head-to-head RCT comparing different formulations of IVIG, regardless of the target condition and outcomes investigated. Two reviewers screened 4084 citations retrieved from MEDLINE, Embase, Cochrane and LILACS, and 23 citations were fully-text evaluated. Eight trials were included. The clinical conditions, outcomes and risk of bias were assessed. Of the eight trials included only two investigated products that are currently on the market. One evaluated two Grifols brands used in patients with primary immunodeficiency and another evaluated two Baxter brands used in patients with chronic inflammatory demyelinating polyradiculoneuropathy. There were no differences between the formulations for the outcomes evaluated. In the other trials, either the manufacturers were acquired by other companies or the formulation was withdrawn from the market. As consequence, evidence concerning these products could not be considered. The quality of the studies was low, showing high risk of bias. Direct evidence about the different IVIGs is scarce and, at present, there is no scientific evidence that can be applied for a specific brand or formulation. Further comparative effectiveness studies are highly desirable for a better understanding of the differences in safety and efficacy of IVIGs.
authors.affiliation: Hospital Alemao Oswaldo Cruz, Institute of Health Education and Science, Rua João Juliao, 245, First floor, 01323-903 Sao Paulo, SP, Brazil. Electronic address: abuehler@haoc.com.br.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Buehler
authors.affiliation: Hospital Alemao Oswaldo Cruz, Institute of Health Education and Science, Rua João Juliao, 245, First floor, 01323-903 Sao Paulo, SP, Brazil. Electronic address: uprync@haoc.com.br.
authors.forename: Uri P
authors.initials: UP
authors.lastname: Flato
authors.affiliation: Hospital Alemao Oswaldo Cruz, Institute of Health Education and Science, Rua João Juliao, 245, First floor, 01323-903 Sao Paulo, SP, Brazil. Electronic address: cferri@haoc.com.br.
authors.forename: Cleusa P
authors.initials: CP
authors.lastname: Ferri
authors.affiliation: Hospital Alemao Oswaldo Cruz, Institute of Health Education and Science, Rua João Juliao, 245, First floor, 01323-903 Sao Paulo, SP, Brazil. Electronic address: jeffersonfernandes@haoc.com.br.
authors.forename: Jefferson G
authors.initials: JG
authors.lastname: Fernandes
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000737:chemistry*; D016032:Randomized Controlled Trials as Topic; D012449:Safety
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: Efficacy; Head-to-head randomized controlled trials; Intravenous immunoglobulins; Systematic review