Doets Alex Y, Hughes Richard Ac, Brassington Ruth, Hadden Robert Dm, Pritchard Jane
Erasmus University Medical Centre, P.O. Box 2040, University Medical Centre Rotterdam, Rotterdam, Netherlands, 3000 CA.
National Hospital for Neurology and Neurosurgery, MRC Centre for Neuromuscular Diseases, PO Box 114, Queen Square, London, UK, WC1N 3BG.
Cochrane Database Syst Rev. 2020 Jan 25;1(1):CD008630. doi: 10.1002/14651858.CD008630.pub5.
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.
AUTHORS' CONCLUSIONS: 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.
血浆置换和静脉注射免疫球蛋白对吉兰-巴雷综合征(GBS)有益,但皮质类固醇则不然。其他药物的疗效尚不清楚。本综述首次发表于2011年,此前于2013年和2016年进行过更新。
评估除血浆置换、静脉注射免疫球蛋白和皮质类固醇之外的药物对GBS的影响。
2019年10月28日,我们检索了Cochrane神经肌肉专业注册库、Cochrane系统评价数据库、医学期刊数据库和Embase中有关GBS治疗的文献。我们还检索了临床试验注册库。
我们纳入了所有类型和严重程度的急性GBS(发病四周内)、所有年龄段个体的随机对照试验(RCT)或半随机对照试验。我们排除了仅研究皮质类固醇、静脉注射免疫球蛋白或血浆置换的试验。我们纳入了与未治疗、安慰剂或其他治疗相比的其他药物治疗或联合治疗试验。
我们遵循Cochrane标准方法学。
我们发现六项涉及五种不同干预措施的试验符合纳入本综述的标准。这些试验在加拿大、中国、德国、日本和英国的医院进行,共纳入151名参与者。所有试验均将16岁及以上参与者(干预组平均或中位年龄为36至57岁,对照组为34至60岁)随机分组,这些参与者患有严重GBS,定义为无法独立行走;一项试验还将仍能独立行走的轻度GBS患者随机分组。本次更新时我们识别出两项新试验。本综述的主要结局指标为随机分组四周后残疾等级改善情况。六项试验中有四项在至少一个方面存在高偏倚风险。我们评估了残疾等级平均改善结局的所有证据,确定性极低,表示我们无法从数据中得出任何结论:一项纳入19名参与者的RCT比较了干扰素β-1a(IFNb-1a)和安慰剂,四周后IFNb-1a是否能改善残疾情况尚不确定(平均差(MD)-0.1;95%置信区间-1.58至1.38;极低确定性证据);一项纳入10名参与者的试验比较了脑源性神经营养因子(BDNF)和安慰剂,四周后BDNF是否能改善残疾情况尚不确定(MD为0.75;95%置信区间-1.14至2.64;极低确定性证据);一项纳入37名参与者的试验比较了脑脊液(CSF)过滤和血浆置换,四周后CSF过滤是否能改善残疾情况尚不确定(MD为0.02;95%置信区间-0.62至0.66;极低确定性证据);一项纳入43名参与者、比较中药雷公藤多苷与皮质类固醇的试验未报告四周后残疾等级改善一级或以上的风险比(RR)但报告了八周后的改善情况;八周后雷公藤多苷是否能改善残疾情况尚不确定(RR为1.47;95%置信区间1.02至2.11;极低确定性证据);我们对两项比较依库珠单抗和安慰剂、共纳入41名参与者的试验进行了Meta分析,四周后依库珠单抗是否能改善残疾情况尚不确定(MD为-0.23;95%置信区间-1.79至1.34;极低确定性证据)。各试验中严重不良事件均不常见,证据分级为低或极低。IFNb-1a与安慰剂相比严重不良事件是否更常见尚不确定(RR为0.92,95%置信区间0.23至3.72;19名参与者),BDNF与安慰剂相比亦如此(RR为1.00,95%置信区间0.28至3.54;10名参与者),CSF过滤与血浆置换相比也不确定(RR为0.13,95%置信区间0.01至2.25;37名参与者)。雷公藤多苷试验未报告严重不良事件。依库珠单抗与安慰剂相比严重不良事件数量可能无明显差异(RR为1.90,0.34至10.50;41名参与者)。我们在六项试验中针对本综述所选的任何结局指标均未发现具有临床意义的差异。然而,样本量较小,因此不能排除具有临床意义的获益或危害。
所有六项RCT规模均过小,无法排除所评估干预措施具有临床意义的获益或危害。所有干预措施和结局的证据确定性均为低或极低。