Conflicting Data on Benefit of IVIG Treatment in MS

Abstracts & Commentary

Synopsis: Intravenous immunoglobulin treatment for the first year from onset of the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measured by brain magnetic resonance imaging.

Sources: Achiron A, et al. Intravenous Immunoglobulin Treatment Following the First Demyelinating Event Suggestive of Multiple Sclerosis. Arch Neurol. 2004;61:1515-1520; Sorensen P, et al. IV Immunoglobulins As Add-on Treatment to Methylprednisolone For Acute Relapses in MS. Neurology. 2004;63:2028-2033; Hommes O, et al. Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis; Randomised Placebo-Controlled Trial. Lancet. 2004;364:1149-1156.

Achiron and colleagues conducted a randomized, placebo-controlled, double-blind study of IVIG within 6 weeks of a first demyelinating event suggestive of multiple sclerosis. Patients received IVIG treatment (2 g/kg loading dose) or placebo and then boosters (0.4 g/kg) every 6 weeks for 1 year. Neurological and clinical assessments were done every 3 months, and a brain MRI was done at the baseline and the end of the study.

The cumulative probability of developing clinically definite MS, ie, a second neurologic event, was lower in the IVIG group vs the placebo group (rate ratio, 0.36 [95% confidence interval 0.15-0.88]; P = 0.03). Patients in the IVIG group also had a reduction in the volume and number of T2- and gadolinium-enhancing lesions (P = 0.01-0.03). Treatment was generally well tolerated.

In a second study, Sorenson and colleagues tested whether IVIG in combination with methylprednisolone facilitated the speed and degree of recovery from an acute MS relapse. Patients were randomly assigned to a single dose of either IVIG (1 g/kg) or placebo 24 hours before treatment, with 1 g/d IV methylprednisolone for 3 consecutive days. Both groups improved, but there was no significant difference between the IVIG and placebo groups in respect to the primary end point of the Expanded Disability Status Scale (EDSS).

In a third study, a large, 2-year European, double-blind, placebo-controlled study of 318 secondary progressive patients (mean age 44 yrs, mean EDSS 5.24, mean percent of patients with a relapse/24 months prior to the study 51.7%). Patients were dosed with IVIG 1g/kg/month or placebo.

IVIG treatment had no beneficial effect on time to confirmed EDSS progression (hazard ratio, 1.11; [95% confidence interval 0.80-1.53] for IVIG vs placebo. The annual relapse rate was 0.46 for both groups. There was no significant difference between the treatment groups for other clinical outcome measures, including the change of T2-lesion load on brain MRI over time.

Commentary

The use of IVIG in the treatment of MS remains controversial, with some neurological advocates, despite conflicting clinical efficacy data. Only 1 study above showed a modest benefit, ie, treating a patient presenting with a first demyelinating event with IVIG every 6 weeks for a year. However, in a similar first-attack study design using weekly interferon beta-1a, there was a substantially better reduction in clinical attacks and brain MRI findings (N Engl J Med. 2000;343:898-904). Thus, the routine use of IVIG for MS in these settings cannot be justified given the availability of other immunomodulatory therapies (interferon-beta, glatiramer acetate, natalizumab) that appear to more beneficial. — Brian R. Apatoff

Dr. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.