RANDOMIZED PLACEBO-CONTROLLED TRIAL OF MONTHLY INTRAVENOUS IMMUNOGLOBULIN THERAPY IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS

Background Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence sugges t beneficial effects of repeated administration of intravenous immunog lobulin (IVIg) by immunomodulating mechanisms and induction or remyeli nation. We aimed to investigate the efficacy of IVIg in a randomised d ouble-blind multicentre study. Methods Patients with relapsing-remitti ng multiple sclerosis were randomly assigned a monthly dose of IVlg (0 .15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years , The primary outcome measures were the effect of treatment on clinica l disability-measured by the absolute change in Kurtzke's expanded dis ability status scale (EDSS) score-and the proportion of patients with improved, stable, or worse clinical disability(greater than or equal t o 1.0 grade on EDSS score). Findings Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or pl acebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in th e placebo group. Intention-to-treat analysis showed that IVIg treatmen t had a beneficial effect on the course of clinical disability. The ED SS score decreased in the IVIg-treated patients and increased in the p lacebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p =0.008). In the IVIg group, the numbers of patients with improved, sta ble, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16% ) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group . Side-effects were reported in three (4%) IVIg-treated patients and i n four (5%) placebo-group patients, but were not directly linked to st udy medication. Interpretation Monthly IVIg is an effective and well-t olerated treatment for patients with relapsing-remitting multiple scle rosis.