Efficacy and safety of double-filtration plasmapheresis treatment of myasthenia gravis: A systematic review and meta-analysis
OBJECTIVES To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.
Therapeutic Plasmapheresis with Albumin Replacement in Alzheimer's Disease and Chronic Progressive Multiple Sclerosis: A Review
Pharmaceuticals (Basel, Switzerland). 2020;13(2)
BACKGROUND Reducing the burden of beta-amyloid accumulation and toxic autoimmunity-related proteins, one of the recognized pathophysiological markers of chronic and common neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis (MS), may be a valid alternative therapy to reduce their accumulation in the brain and thus reduce the progression of these disorders. The objective of this review was to evaluate the efficacy of plasmapheresis (PP) in AD and chronic progressive MS patients (in terms of improving clinical symptoms) and to analyze its safety and protocols. METHODS Articles related to this topic and published without time limitations in the Medline, and Cochrane databases were reviewed. RESULTS In AD patients, PP reduced amyloid beta (Abeta) levels in the brain, accompanied by a tendency towards cognitive stabilization, and improved language and verbal fluency. In regards to structural and functional brain changes, PP reduced brain volume and favored the stabilization, or absence, of the progression of perfusion. In chronic progressive form of MS patients, PP improved neurological deficits in 20-70% of patients with a chronic progressive form of MS, and restored interferon (IFN) responsiveness, which was not accompanied by any image change in brain plaques. CONCLUSIONS Therapeutic plasmapheresis with albumin replacement is a promising strategy for reducing Abeta mediated toxicity and slowing the progression of the disorder. Some patients with chronic progressive forms of MS show improvement in neurological deficits. The features of AD and MS patients who benefit most from this approach need further research.
Plasma Exchange or Immunoadsorption in Demyelinating Diseases: A Meta-Analysis
J Clin Med. 2020;9(5)
Multiple sclerosis (MS) is an inflammatory disease mainly affecting the central nervous system. In MS, abnormal immune mechanisms induce acute inflammation, demyelination, axonal loss, and the formation of central nervous system plaques. The long-term treatment involves options to modify the disease progression, whereas the treatment for the acute relapse has its focus in the administration of high-dose intravenous methylprednisolone (up to 1000 mg daily) over a period of three to five days as a first step. If symptoms of the acute relapse persist, it is defined as glucocorticosteroid-unresponsive, and immunomodulation by apheresis is recommended. However, several national and international guidelines have no uniform recommendations on using plasma exchange (PE) nor immunoadsorption (IA) in this case. A systematic review and meta-analysis was conducted, including observational studies or randomized controlled trials that investigated the effect of PE or IA on different courses of MS and neuromyelitis optica (NMO). One thousand, three hundred and eighty-three patients were included in the evaluation. Therapy response in relapsing-remitting MS and clinically isolated syndrome was 76.6% (95%CI 63.7-89.8%) in PE- and 80.6% (95%CI 69.3-91.8%) in IA-treated patients. Based on the recent literature, PE and IA may be considered as equal treatment possibilities in patients suffering from acute, glucocorticosteroid-unresponsive MS relapses.
Multiple sclerosis (MS) and neuromyelitis optica (NMO) patients (41 studies, n=1383).
Plasma exchange (PE).
Therapy response in relapsing-remitting multiple sclerosis and clinically isolated syndrome was 76.6% in PE- and 80.6% in IA-treated patients. Therapy response in NMO was 72.5% in PE-treated patients, and 100% in IA-treated patients.
Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-Barre syndrome
The Cochrane database of systematic reviews. 2020;1:Cd008630
BACKGROUND Plasma exchange and intravenous immunoglobulin, but not corticosteroids, are beneficial in Guillain-Barre syndrome (GBS). The efficacy of other pharmacological agents is unknown. This review was first published in 2011 and previously updated in 2013, and 2016. OBJECTIVES To assess the effects of pharmacological agents other than plasma exchange, intravenous immunoglobulin and corticosteroids for GBS. SEARCH METHODS 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. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. MAIN RESULTS 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.
Clinical usefulness of prethymectomy plasmapheresis in patients with myasthenia gravis: a systematic review and meta-analysis
Interactive cardiovascular and thoracic surgery. 2019
OBJECTIVES Our goal was to evaluate, through a systematic review, the efficacy of plasmapheresis in the preoperative preparation of the patient for a thymectomy for the treatment of myasthenia gravis. METHODS MEDLINE, Embase, LILACS, Scopus and CENTRAL databases were searched. The following outcomes were evaluated: myasthenic crisis, mortality, pneumonia, bleeding, use of mechanical ventilation, length of hospital stay and intensive care unit (ICU) stay. RevMan 5.3 software provided by the Cochrane Collaboration was used for the meta-analysis. RESULTS The total number of patients evaluated in the 7 included studies was 360. Plasmapheresis during the preoperative period did not decrease the myasthenic crisis [risk ratio (RR) 0.36, 95% confidence interval (CI) 0.08-1.66; I2 = 44%; 5 studies, 243 patients]. There was also no change in the mortality rate (RR 0.7, 95% CI 0.11-4.62; I2 = 0%; 3 studies, 172 patients) or pneumonia cases (RR 0.28, 95% CI 0.07-1.09; I2 = 27%; 5 studies, 272 patients). Bleeding was greater in patients who underwent plasmapheresis (mean difference 34.34 ml; 95% CI 24.93-43.75; I2 = 0%). We evaluated the following outcomes: need for mechanical ventilation, hospital stay, ICU stay and mechanical ventilation, but these outcomes were not adequate to perform the meta-analysis due to the high heterogeneity among the studies. Subgroup analysis showed that plasmapheresis performed during the preoperative period in patients with severe disease (Osserman III and IV) decreased the myasthenic crisis postoperatively (RR 0.12, 95% CI 0.02-0.65; I2 = 63%). CONCLUSIONS Plasmapheresis may reduce the myasthenic crisis during the postoperative period in patients with severe disease but may produce little or no difference in patients with mild clinical expression of the disease.
Plasma exchange for Guillain-Barre syndrome
The Cochrane Database of Systematic Reviews. 2017;((2)):CD001798.
BACKGROUND Guillain-Barre syndrome (GBS) is an acute paralysing disease caused by peripheral nerve inflammation. This is an update of a review first published in 2001 and last updated in 2012. OBJECTIVES To assess the effects of plasma exchange for treating GBS. SEARCH METHODS On 18 January 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched clinical trials registries. SELECTION CRITERIA Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment, or comparing different regimens or techniques of plasma exchange. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. MAIN RESULTS In the first version of this review there were six eligible trials concerning 649 participants comparing plasma exchange with supportive treatment. No new eligible trials have been identified in subsequent updates. Two other studies compared different numbers of plasma exchanges. Overall the included trials had a moderate risk of bias (in general, the studies were at low risk but all had a high risk of bias from lack of blinding).In one trial with 220 severely affected participants, the median time to recover walking with aid was significantly shorter with plasma exchange (30 days) than without plasma exchange (44 days). In another trial with 91 mildly affected participants, the median time to onset of motor recovery was significantly shorter with plasma exchange (six days) than without plasma exchange (10 days). After four weeks, moderate-quality evidence from the combined data of three trials accounting for a total of 349 patients showed that plasma exchange significantly increased the proportion of patients who recovered the ability to walk with assistance (risk ratio (RR) 1.60, 95% confidence interval (CI) 1.19 to 2.15).In five trials with 623 participants in total, moderate-quality evidence showed that the RR for improvement by one or more disability grades after four weeks was 1.64 (95% CI 1.37 to 1.96) times greater with plasma exchange. Participants treated with plasma exchange also fared better, according to moderate-quality evidence, in time to recover walking without aid (three trials with 349 participants; RR 1.72, 95% CI 1.06 to 2.79) and requirement for artificial ventilation (five trials with 623 participants; RR 0.53, 95% CI 0.39 to 0.74). More participants had relapses by the end of follow-up in the plasma exchange group than in the control group (six trials with 649 participants; RR 2.89, 95% CI 1.05 to 7.93; moderate-quality evidence). Despite this, according to moderate-quality evidence, the likelihood of full muscle strength recovery at one year was greater with plasma exchange than without plasma exchange (five trials with 404 participants; RR 1.24, 95% CI 1.07 to 1.45), and the likelihood of severe motor sequelae was less (six trials with 649 participants; RR 0.65, 95% CI 0.44 to 0.96). High-quality evidence from six trials with 649 participants could not confirm or refute a lower risk of death following plasma exchange compared to control (RR 0.86, 95% CI 0.45 to 1.65).Three trials (N = 556) provided details of serious adverse events during the hospital stay; combined analyses found no increase in serious infectious events compared to the control group (RR 0.91, 95% CI 0.73 to 1.13), nor were there clear differences in blood pressure instability, cardiac arrhythmias or pulmonary emboli. AUTHORS' CONCLUSIONS Moderate-quality evidence shows significantly more improvement with plasma exchange than with supportive care alone in adults with Guillain-Barre syndrome, without a significant increase in serious adverse events. According to moderate-quality evidence, there was a small but significant increase in the risk of relapse during the first six to 12 months after onset in people treated with plasma exchange compared with those who were not treated. Despite this, after one year, full recovery of muscle strength was more likely and severe residual weakness less likely with plasma exchange.
Plasmapheresis for refractory status epilepticus, part I: a scoping systematic review of the adult literature
PURPOSE Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in adults. METHODS Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Twenty-two original articles were identified. Twenty-seven adult patients were described in these articles, with a variety of autoimmune conditions leading to RSE. Seizure response with the application of PE therapy occurred in 14 of the 27 patients (51.9%), with 1 (3.7%) and 13 (48.1%) displaying partial and complete responses respectively. Generalized RSE was the most likely seizure subtype to respond to PE therapy. One patient had recorded an adverse events related to PE therapy. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest an uncertain response of adult autoimmune RSE to PE therapy. Thus, the routine application of PE therapy for adult autoimmune RSE cannot be recommended at this time.
Plasmapheresis for refractory status epilepticus part II: a scoping systematic review of the pediatric literature
BACKGROUND Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in children. METHODS Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Twenty-two original articles were identified, with 37 pediatric patients. The mean age of the patients was 8.3 years (age median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%) displaying resolution of seizures and 2 patients (5.4%) displaying a partial reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no response to PE therapy. No adverse events were recorded. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest little to no benefit of PE in pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended at this time.
Human immunoglobulin versus plasmapheresis in guillain-barre syndrome and myasthenia gravis: a meta-analysis
Journal of Clinical Neuromuscular Disease. 2016;18((1)):1-11.
OBJECTIVES To evaluate the efficacy and safety over a short time period of human intravenous immunoglobulin versus plasma exchange (PE) in the management of some autoimmune neurologic diseases. In addition, length of hospital stay and duration of ventilator support were compared. METHODS Randomized controlled trials and analytical observational studies of more than 10 cases were reviewed. Cochrane Neuromuscular Disease Group trials, MEDLINE, EMBASE, HINARI, and Ovid, were searched as data source. Reference lists were examined for further relevant articles. A random-effect model was used to derive a pooled risk ratio. RESULTS A total of 552 articles were found and 24 met the criteria for a studied population of 4657 cases: 14 articles were about Guillain-Barre syndrome and 10 of myasthenia gravis. No evidence was found to suggest that PE or intravenous immunoglobulin differed in terms of efficacy or safety to treat any of the 2 diseases. Hospital stay length and ventilatory support time are different in each illness; however, we found no statistical difference in either of the 2 treatments. CONCLUSIONS There is no evidence for superiority in the efficacy or safety of immunoglobulin or plasmapheresis in the management of Guillain-Barre syndrome and myasthenia gravis. However, caution should be exercised in the interpretation of these results given the limitations in the quality of the evidence and the heterogeneity of the studies.
Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy
Cochrane Database of Systematic Reviews.. 2015;((8)):CD003906.
BACKGROUND Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon progressive or relapsing paralysing disease caused by inflammation of the peripheral nerves. If the hypothesis that it is due to autoimmunity is correct, removal of autoantibodies in the blood by plasma exchange should be beneficial. OBJECTIVES To assess the effects of plasma exchange for treating CIDP. SEARCH METHODS On 30 June 2015, we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also scrutinised the bibliographies of the trials, contacted the trial authors and other disease experts, and searched trials registries for ongoing studies. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-RCTs in participants of any age comparing plasma exchange with sham treatment or no treatment. DATA COLLECTION AND ANALYSIS Two review authors independently selected the trials, extracted the data, and assessed risk of bias. Where possible the review authors combined data according to the methods of the Cochrane Neuromuscular Disease Review Group. MAIN RESULTS PRIMARY OUTCOME MEASURE one cross-over trial including 18 participants showed after four weeks, 2 (95% confidence interval (CI) 0.8 to 3.0) points more improvement on an 11-point disability scale with plasma exchange (10 exchanges over four weeks) than with sham exchange. Rapid deterioration after plasma exchange occurred in eight of 12 who had improved. SECONDARY OUTCOME MEASURES when we combined the results of this cross-over trial and a trial with 29 participants treated in a parallel-group design, there were 31 points (95% CI 16 to 45) more improvement on an impairment scale (maximum score 280) after plasma exchange (six exchanges over three weeks) than after sham exchange. There were significant improvements in both trials in an electrophysiological measure, the proximally evoked compound muscle action potential, after three or four weeks. Nonrandomised evidence indicates that plasma exchange induces adverse events in 3% to 17% of procedures. These events are sometimes serious. Both trials had a low risk of bias. A trial that showed no significant difference in the benefit between plasma exchange and intravenous immunoglobulin is included in the Cochrane review of intravenous immunoglobulin for this condition. AUTHORS' CONCLUSIONS Moderate- to high-quality evidence from two small trials shows that plasma exchange provides significant short-term improvement in disability, clinical impairment, and motor nerve conduction velocity in CIDP but rapid deterioration may occur afterwards. Adverse events related to difficulty with venous access, use of citrate, and haemodynamic changes are not uncommon. We need more research to identify agents that will prolong the beneficial action of plasma exchange.