Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial.
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.
Fazekas
F
F
Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. franz.fazekas@meduni-graz.at
Lublin
F D
FD
Li
D
D
Freedman
M S
MS
Hartung
H P
HP
Rieckmann
P
P
Sørensen
P Soelberg
PS
Maas-Enriquez
M
M
Sommerauer
B
B
Hanna
K
K
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
D016756:Immunoglobulins, Intravenous; D010919:Placebos