Review question
We reviewed the evidence for drug treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for people with Guillain-Barré syndrome (GBS).
Background
GBS is an acute (sudden and severe), paralysing disease caused by inflammation of the nerves (damage that occurs due to the body's immune system). Symptoms reach their worst within four weeks of onset. Between 3% and 17% of people with GBS die of its complications. A quarter need a ventilator to help with breathing. Recovery takes several weeks or months and is often incomplete. Plasma exchange (washing harmful substances out of the blood) and intravenous immunoglobulin (human antibodies harvested from blood donations given through a drip) can help speed up the recovery. Corticosteroids are probably not effective. Despite the use of plasma exchange or intravenous immunoglobulin many people with GBS have long-term disability. We need to find what other treatments have been tried as a basis for launching new trials.
Study characteristics
Cochrane Review authors collected and analysed all relevant randomised controlled trials (RCTs) to answer the review question. In RCTs people are allocated to treatment groups at random, which reduces bias. We found six eligible RCTs testing five different treatments in a total of 151 participants. We were uncertain about the evidence from the trials. One RCT with only 19 participants compared interferon beta-1a (a drug that is beneficial in multiple sclerosis) with placebo (a sham treatment). Another, with only 10 participants, compared a nerve growth factor which, in theory, should be beneficial in people with GBS, with placebo. A third trial, with 37 participants, compared cerebrospinal fluid filtration (washing the nerve roots around the spinal cord) with plasma exchange. A fourth trial with 43 participants compared the Chinese herbal medicine tripterygium polyglycoside, which is thought to have anti-inflammatory properties, with corticosteroids. A fifth trial with eight participants and a sixth with 34 participants compared eculizumab (a drug that blocks complement, a key inflammatory component) with placebo. Five trials received commercial company support. Support for the trial of the Chinese herbal medicine is unknown.
Key results and certainty of the evidence
None of these trials was large enough to confirm or refute the benefit or harm of any of these drugs in the treatment of people with acute GBS. The only trial that found a difference between treatments was the Chinese herbal medicine trial: participants receiving the herbal medicine were one and a half times more likely to have improved disability after eight weeks than those receiving corticosteroids. However, this estimate was uncertain and the trial authors did not report other clinical outcomes. Serious adverse events were uncommon with each of the five treatments investigated in the identified trials and rates were not different from those in the control groups. We identified very little evidence other than that from RCTs.
There is a need to develop and test new treatments for GBS, and to adopt more sensitive outcome measures.
The evidence is up to date to October 2019.
All six RCTs were too small to exclude clinically important benefit or harm from the assessed interventions. The certainty of the evidence was low or very low for all interventions and outcomes.
Plasma exchange and intravenous immunoglobulin, but not corticosteroids, are beneficial in Guillain-Barré syndrome (GBS). The efficacy of other pharmacological agents is unknown. This review was first published in 2011 and previously updated in 2013, and 2016.
To assess the effects of pharmacological agents other than plasma exchange, intravenous immunoglobulin and corticosteroids for GBS.
On 28 October 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase for treatments for GBS. We also searched clinical trials registries.
We included all randomised controlled trials (RCTs) or quasi-RCTs of acute GBS (within four weeks from onset) of all types and degrees of severity, and in individuals of all ages. We discarded trials that investigated only corticosteroids, intravenous immunoglobulin or plasma exchange. We included other pharmacological treatments or combinations of treatments compared with no treatment, placebo or another treatment.
We followed standard Cochrane methodology.
We found six trials of five different interventions eligible for inclusion in this review. The trials were conducted in hospitals in Canada, China, Germany, Japan and the UK, and included 151 participants in total. All trials randomised participants aged 16 years and older (mean or median age in the trials ranged from 36 to 57 years in the intervention groups and 34 to 60 years in the control groups) with severe GBS, defined by the inability to walk unaided. One trial also randomised patients with mild GBS who were still able to walk unaided. We identified two new trials at this update.The primary outcome measure for this review was improvement in disability grade four weeks after randomisation. Four of six trials had a high risk of bias in at least one respect.
We assessed all evidence for the outcome mean improvement in disability grade as very low certainty, which means that we were unable to draw any conclusions from the data. One RCT with 19 participants compared interferon beta-1a (IFNb-1a) and placebo. It is uncertain whether IFNb-1a improves disability after four weeks (mean difference (MD) -0.1; 95% CI −1.58 to 1.38; very low-certainty evidence). A trial with 10 participants compared brain-derived neurotrophic factor (BNDF) and placebo. It is uncertain whether BDNF improves disability after four weeks (MD 0.75; 95% CI −1.14 to 2.64; very low-certainty evidence). A trial with 37 participants compared cerebrospinal fluid (CSF) filtration and plasma exchange. It is uncertain whether CSF filtration improves disability after four weeks (MD 0.02; 95% CI −0.62 to 0.66; very low-certainty evidence). One trial that compared the Chinese herbal medicine tripterygium polyglycoside with corticosteroids with 43 participants did not report the risk ratio (RR) for an improvement by one or more disability grade after four weeks, but did report improvement after eight weeks. It is uncertain whether tripterygium polyglycoside improves disability after eight weeks (RR 1.47; 95% CI 1.02 to 2.11; very low-certainty evidence). We performed a meta-analysis of two trials comparing eculizumab and placebo with 41 participants. It is uncertain whether eculizumab improves disability after four weeks (MD -0.23; 95% CI −1.79 to 1.34; very low-certainty evidence). Serious adverse events were uncommon in each of the trials and evidence was graded as either low or very low. It is uncertain whether serious adverse events were more common with IFNb-1a versus placebo (RR 0.92, 95% CI 0.23 to 3.72; 19 participants), BNDF versus placebo (RR 1.00, 95% CI 0.28 to 3.54; 10 participants) or CSF filtration versus plasma exchange (RR 0.13, 95% CI 0.01 to 2.25; 37 participants). The trial of tripterygium polyglycoside did not report serious adverse events. There may be no clear difference in the number of serious adverse events after eculizumab compared to placebo (RR 1.90, 0.34 to 10.50; 41 participants). We found no clinically important differences in any of the outcome measures selected for this review in any of the six trials. However, sample sizes were small and therefore clinically important benefit or harm cannot be excluded.