title: Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial.
abstract: OBJECTIVE
  Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety.
  
  
  METHODS
  One hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo-controlled trial. Forty-four and 42 patients received treatment with 0.2 and 0.4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0.1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity assessed by 6-weekly MRI.
  
  
  RESULTS
  Baseline variables were similar in IVIG- and placebo-treated groups. After 1 year, the proportion of relapse-free patients did not differ statistically according to treatment (IVIG 0.2 g/kg: 57%; IVIG 0.4 g/kg: 60%; placebo: 68%), and there was no difference regarding the cumulative number of unique newly active MRI lesions (median numbers: IVIG 0.2 g/kg: 8.0; IVIG 0.4 g/kg: 5.0; placebo: 7.2) after 48 weeks. There were no significant between-group differences in the rates of adverse events.
  
  
  CONCLUSIONS
  Although IV immunoglobulin (IVIG) treatment was well tolerated, this study did not substantiate a beneficial effect of IVIG in doses ranging from 0.2 to 0.4 g/kg. This result seriously questions the utility of IVIG for the treatment of relapsing-remitting multiple sclerosis.
authors.affiliation: Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. franz.fazekas@meduni-graz.at
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: F D
authors.initials: FD
authors.lastname: Lublin
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
authors.forename: P
authors.initials: P
authors.lastname: Rieckmann
authors.forename: P Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.forename: M
authors.initials: M
authors.lastname: Maas-Enriquez
authors.forename: B
authors.initials: B
authors.lastname: Sommerauer
authors.forename: K
authors.initials: K
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D007167:Immunotherapy / Q000379:methods*; D007262:Infusions, Intravenous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D010919:Placebos; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous; D010919:Placebos