Abstract
BACKGROUND: From animal experiments, there is evidence to suggest that intravenous immunoglobulins can reverse some of the disease process of central nervous system demyelination. Subsequently, clinical trials of intravenous immunoglobulins have been conducted in people with multiple sclerosis (MS). OBJECTIVES: To identify and summarise the evidence that intravenous immunoglobulins are safe and beneficial for people with MS. SEARCH STRATEGY: We searched the Cochrane Multiple Sclerosis Group trials Register( January 2003) The Cochrane Central Register of Controlled Trials (The Cochrane Library issue 4, 2002), MEDLINE (January 1966 to April 2001), EMBASE (January 1988 to April 2001) and reference lists of articles. We also contacted relevant pharmaceutical companies and authors of identified trials. SELECTION CRITERIA: Randomised controlled trials of intravenous immunoglobulins for the secondary prevention of relapses and disease progression in MS. DATA COLLECTION AND ANALYSIS: 913 titles and abstracts were obtained from the literature search, and we eventually identified 10 clinical trials. All reviewers agreed on the final dataset for entry into RevMan 4.1, and summarised the results. Study authors were contacted for additional information but no response was obtained. MAIN RESULTS: Of 913 potential studies, 10 trials were identified with a total of 918 participants, four of which are in progress or awaiting publication. The remaining six trials were suitable for consideration by this review (344 participants). Only two trials met our protocol's inclusion criteria. The four remaining trials were excluded as they did not use outcome measures specified in our review (2 trials, 122 participants), or were of insufficient methodological quality (2 trials, 34 participants). From the two included trials (168 participants) there was a reduction in relapse rate and increased time to first relapse during treatment with intravenous immunoglobulins, but reliable disease progression outcomes were not reported, nor were magnetic resonance imaging (MRI) data available to support clinical information. There may be as many as 574 participants in ongoing or yet to be published trials. REVIEWER'S CONCLUSIONS: There is some evidence to support use of intravenous immunoglobulins as a preventative treatment for relapses in relapsing remitting MS, but further studies should be performed using MRI and disease progression endpoints. It may be possible to draw more robust conclusions when ongoing or recently completed trials make their data available for review. Two rigorously conducted trials with a total of 122 participants did not demonstrate a positive clinical benefit, but were excluded from this review as they employed outcome measures not specified in our protocol. Immunoglobulins were well tolerated with a less than 5% risk of adverse events in participants in included trials.