Intravenous immunoglobulin (IVIg) is a treatment in which antibodies from donated blood are injected into a person's vein. We wanted to find out whether IVIg can speed up recovery from Guillain-Barré syndrome (GBS).
GBS is an uncommon disease of the nerves outside the brain and spinal cord. It causes weakness, numbness and breathing difficulty. Another Cochrane review has shown that plasma exchange (PE) works better than supportive care alone in GBS. In PE, the liquid part of a person’s blood (plasma) is replaced with a plasma substitute to remove antibodies.
We included trials of IVIg compared to no treatment, dummy treatment, PE, immunoabsorption (in which specific antibodies are removed from blood) or other immune treatments. We also considered trials of IVIg added to another treatment. We found 12 trials. Some of these compared more than two treatments.
- Seven trials compared IVIg with PE (in 623 participants with severe GBS).
- One compared PE alone to PE followed by IVIg (in 249 participants).
- Three compared IVIg with supportive care (in a total of 75 children).
- One compared a two-day to a five-day IVIg treatment plan (in 51 children).
- One compared IVIg with immunoabsorption (in 48 participants).
- One compared IVIg plus immunoabsorption with immunoabsorption (in 34 participants).
For this review, we chose change in a disability scale after four weeks’ treatment as the main measure of the effect of IVIg.
Key results and quality of the evidence
Five of the trials comparing IVIg and PE measured change in disability. IVIg and PE produced a similar amount of improvement in disability in the 536 trial participants. This evidence was of moderate quality. Harmful effects were no more frequent with PE or IVIg, but people were more likely to finish a course of IVIg.
In one trial involving 249 participants who received PE or PE followed by IVIg, there was slightly more improvement from PE and IVIg together. The effect was probably not large enough to be noticeable but the results do not rule out the possibility. This evidence was of moderate quality.
Three studies in children suggested that IVIg speeds up recovery compared with supportive care. Only one used the disability scale. They provided low quality evidence.
Small trials in children showed more improvement in disability with high-dose than low-dose IVIg but the size of the trials does not permit a firm conclusion. The effect on disability appeared similar with a standard dose over two days rather than five days.
Giving IVIg after immunoabsorption provided no extra benefit over immunoabsorption alone. No conclusions can be drawn from the trial comparing IVIg with immunoabsorption.
The risk of bias in the included studies was variable.
More research is needed to find the best dose of IVIg in adults and children, and one trial of giving a second dose to people who otherwise would be expected to do badly is in progress.
The evidence is current to December 2013.
A previous Cochrane review has shown that PE hastens recovery compared with supportive treatment alone. There are no adequate comparisons of IVIg with placebo in adults, but this review provides moderate quality evidence that, in severe disease, IVIg started within two weeks from onset hastens recovery as much as PE. Adverse events were not significantly more frequent with either treatment but IVIg is significantly much more likely to be completed than PE. Also, according to moderate quality evidence, giving IVIg after PE did not confer significant extra benefit. In children, according to low quality evidence, IVIg probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in patients whose treatment starts more than two weeks after onset. Dose-ranging studies are also needed and one is in progress.
Guillain-Barré syndrome (GBS) is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin (IVIg) is beneficial in other autoimmune diseases. This is an update of a review first published in 2001 and previously updated in 2003, 2005, 2007, 2010 and 2012. Other Cochrane systematic reviews have shown that plasma exchange (PE) significantly hastens recovery in GBS compared with supportive treatment alone, and that corticosteroids alone are ineffective.
We had the following four objectives.
1. To examine the efficacy of intravenous immunoglobulin (IVIg) in hastening recovery and reducing the long-term morbidity from Guillain-Barré syndrome (GBS).
2. To determine the most efficacious dose of IVIg in hastening recovery and reducing the long-term morbidity from GBS.
3. To compare the efficacy of IVIg and plasma exchange (PE) or immunoabsorption in hastening recovery and reducing the long-term morbidity from GBS.
4. To compare the efficacy of IVIg added to PE with PE alone in hastening recovery and reducing the long-term morbidity from GBS.
We searched the Cochrane Neuromuscular Disease Group Specialized Register (2 December 2013), CENTRAL (2013, Issue 12 in The Cochrane Library), MEDLINE (January 1966 to November 2013) and EMBASE (January 1980 to November 2013). We checked the bibliographies in reports of the randomised trials and contacted the authors and other experts in the field to identify additional published or unpublished data.
Randomised and quasi-randomised trials of IVIg compared with no treatment, placebo treatment, PE, or other immunomodulatory treatments in children and adults with GBS of all degrees of severity. We also included trials in which IVIg was added to another treatment.
Two authors independently selected papers, extracted data and assessed quality. We collected data about adverse events from the included trials.
Twelve trials were found to be eligible for inclusion in this review. Seven trials with a variable risk of bias compared IVIg with PE in 623 severely affected participants. In five trials with 536 participants for whom the outcome was available, the mean difference (MD) of change in a seven-grade disability scale after four weeks was not significantly different between the two treatments: MD of 0.02 of a grade more improvement in the intravenous immunoglobulin than the plasma exchange group; 95% confidence interval (CI) 0.25 to -0.20. There were also no statistically significant differences in the other measures considered. Three studies including a total of 75 children suggested that IVIg significantly hastens recovery compared with supportive care. The primary outcome for this review, available for only one trial with 21 mildly affected children, showed significantly more improvement in disability grade after four weeks with IVIg than supportive treatment alone, MD 1.42, 95% CI 2.57 to 0.27.
In one trial involving 249 participants comparing PE followed by IVIg with PE alone, the mean grade improvement was 0.2 (95% CI -0.14 to 0.54) more in the combined treatment group than in the PE alone group; not clinically significantly different, but not excluding the possibility of significant extra benefit. Another trial with 34 participants comparing immunoabsorption followed by IVIg with immunoabsorption alone did not reveal significant extra benefit from the combined treatment.
Adverse events were not significantly more frequent with either treatment, but IVIg is significantly much more likely to be completed than PE.
Small trials in children showed a trend towards more improvement with high-dose compared with low-dose IVIg, and no significant difference when the standard dose was given over two days rather than five days.