Intravenous immunoglobulins in multiple sclerosis: Results of the Austrianimmunoglobulin in multiple sclerosis (AIMS) trial

Background: Multiple sclerosis (MS) is an autoimmune disorder characterized by inflammatory demyelinating lesions in the central nervous system. Open studies and experimental evidence suggest beneficial effects of intravenous immunoglobulin (IVIG) by immunomodulating mechanisms and induction of remy elination. Patients and Methods: In this randomized, double-blind, placebo- controlled multicenter trial we tested the efficacy of monthly IVIG in 150 patients with relapsing MS. Primary outcome measures were the effect on cli nical disability as measured by the Expanded Disability Status Scale (EDSS) , and the proportion of patients with improved, stable or worsened clinical disability (change by greater than or equal to 1.0 EDSS point) in each tre atment group. Secondary outcome measures included the annual relapse rate a nd the proportion of relapse-free patients, IVIG was given over 2 years in a monthly dosage of 0.15-0.2 g/kg body weight. Results: As shown by intent- to-treat analysis, the EDSS significantly decreased in the IVIG-treated pat ients (-0.23 +/- 0.89) and increased in the placebo-treated patients (+0.12 +/- 1.07). The difference between both groups was statistically significan t (p = 0.008). In the IVIG group 31% of the patients showed improved, 51% s table, and 16% worsened clinical disability. In the placebo group this dist ribution was 14%, 63% and 23%, respectively (p = 0.041). Annual relapse rat es were 0.52 +/- 0.85 in the IVIG and 1.26 +/- 2.2 in the placebo group (p = 0.0037). The proportion of relapse-free patients receiving IVIG was 53% v s. 36% of patients in the placebo group (p = 0.03). Adverse events occurred in 4% of patients in the IVIG group and in 5% of patients receiving placeb o and did not appear to be directly related to the medication, Conclusion: This study demonstrates that monthly IVIG at a dosage of 0.15-0.2 g/kg body weight improves clinical disability and reduces the frequency of relapses without major side effects in relapsing Rns.