Use of Intravenous Immunoglobulin for Treatment of Neurological Conditions: A Systematic Review.

Abstract

Purpose: Given the increasing use of intravenous immunoglobulin for various neurological conditions, its significant cost and the uncertainty pertaining to its benefits and harms, we conducted a systematic review of randomized controlled trials that compared intravenous immunoglobulin to other current therapies.Methods: A systematic search strategy of Medline (1966-June 2003) and the Cochrane Registry of Controlled Trials (June 2003 edition) was developed to identify randomised controlled trials. Two authors (BH, DF) independently reviewed all citations retrieved from the electronic search to identify all potentially relevant trials for this review. In cases where a unanimous decision could not be reached, a third party was consulted. To be eligible, studies had to be randomised controlled trials comparing intravenous immunoglobulin to either placebo or an active control and evaluating clinical outcomes. Measures of effect were calculated for each trial independently, and studies were pooled based on clinical and methodologic judgment as to its appropriateness. Fixed effects and random effects models were selected for each meta-analysis based on appraisal of the clinical homogeneity of patients across studies, as well as from testing for heterogeneity between studies. In circumstances where pooling of trials was inappropriate or not feasible, a qualitative discussion of the findings was developed.Results: Thirty-seven trials representing 14 conditions were identified. Results from meta-analysis suggest that intravenous immunoglobulin therapy is effective for the treatment of multiple sclerosis (pooled 1-year EDSS change −0.46, 95% CI [−0.92,0.01] in favor of IVIG; pooled change in annual exacerbation rate −0.82, 95% CI [−1.54, −0.11] in favor of IVIG; pooled odds of remaining exacerbation free 0.24, 95% CI [0.12, 0.50] in favor of IVIG ) and idiopathic chronic inflammatory demyelinating polyneuropathy (pooled change in disability score −0.67, 95% CI [−1.04, −0.30] in favor of IVIG; pooled odds of achieving treatment response 4.43, 95% CI [2.20, 8.91] in favor of IVIG). There was insufficient evidence to determine whether this therapy was more effective for Guillain-Barré Syndrome than plasma exchange (pooled change in disability score −0.11, 95% CI [−0.37,0.14]; pooled odds of improving by 1 or more grades on the Hughes disability scale 1.91, 95% CI [1.11, 3.28] in favor of IVIG; pooled odds of mortality 0.84, 95% CI [0.31, 2.29]). There was also insufficient evidence regarding paraprotein-associated chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. No evidence of benefit was observed for inclusion body myositis and myasthenia gravis. Based on evidence from lone randomised trials, there also exists evidence indicating that IVIG may be useful for treatment of dermatomyositis, stiff person syndrome and Lambert-Eaton Syndrome.