Meta-analysis of the effectiveness of relapse prevention therapy for myelin-oligodendrocyte glycoprotein antibody-associated disease
Multiple sclerosis and related disorders. 2023;72:104571
BACKGROUND Approximately 40% of adults and 30% of children with Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) experience a relapsing course, but the optimal relapse prevention therapy remains unclear. A meta- analysis was conducted to investigate the efficacy of azathioprine (AZA), mycophenolate mofetil (MMF), rituximab (RTX), maintenance intravenous immunoglobulin (IVIG), and tocilizumab (TCZ) in prevention of attacks in MOGAD. METHODS English and Chinese-language articles published from January 2010 to May 2022 were searched in PubMed, Embase, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CQVIP). Studies with fewer than three cases were excluded. Meta-analysis of the relapse-free rate, the change of annualized relapse rate (ARR)and Expanded Disability Status Scale (EDSS) scores before and after treatment, and an age subgroup analysis was performed. RESULTS A total of 41 studies were included. Three were prospective cohort studies, one was an ambispective cohort study, and 37 were retrospective cohort studies or case series. Eleven, eighteen, eighteen, eight, and two studies were included in the meta-analysis for relapse-free probability after AZA, MMF, RTX, IVIG, and TCZ therapy, respectively. The proportions of patients without relapse after AZA, MMF, RTX, IVIG, and TCZ were 65% [95% confidence interval (CI):49%-82%]), 73% (95%CI:62%-84%), 66% (95%CI:55%-77%), 79% (95%CI:66%-91%), and 93% (95%CI:54%-100%), respectively. The relapse-free rate did not significantly differ between the children and adults treated with each medication. Six, nine, ten, and three studies were included in the meta-analysis for the change of ARR before and after AZA, MMF, RTX, and IVIG therapy, respectively. ARR was significantly decreased after AZA, MMF, RTX, and IVIG therapy with a mean reduction of 1.58 (95%CI: [-2.29--0.87]), 1.32 (95%CI: [-1.57--1.07]), 1.01 (95%CI: [-1.34--0.67]), and 1.84 (95%CI: [-2.66--1.02]), respectively. The change in ARR did not significantly differ between children and adults. CONCLUSIONS AZA, MMF, RTX, maintenance IVIG, and TCZ all reduce the risk of relapse in both pediatric and adult patients with MOGAD. The literatures included in the meta-analysis were mainly retrospective studies, so large randomized prospective clinical trials are needed to compare the efficacy of different treatments.
Prediction Models for Intravenous Immunoglobulin Resistance in Kawasaki Disease: A Meta-analysis
CONTEXT Approximately 10% to 20% of patients with Kawasaki disease (KD) are refractory to initial intravenous immunoglobulin (IVIG) therapy. KD is mainly associated with coronary artery abnormalities. OBJECTIVES To identify and evaluate all developed prediction models for IVIG resistance in patients with KD and synthesize evidence from external validation studies that evaluated their predictive performances. DATA SOURCES PubMed Medline, Dialog Embase, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from inception until October 5, 2021. STUDY SELECTION All cohort studies that reported patients diagnosed with KD who underwent an initial IVIG of 2 g/kg were selected. DATA EXTRACTION Study and patient characteristics and model performance measures. Two authors independently extracted data from the studies. RESULTS The Kobayashi, Egami, Sano, Formosa, and Harada scores were the only prediction models with 3 or more external validation of the161 model analyses in 48 studies. The summary C-statistics were 0.65 (95% confidence interval [CI]: 0.57-0.73), 0.63 (95% CI: 0.55-0.71), 0.58 (95% CI: 0.55-0.60), 0.50 (95% CI: 0.36-0.63), and 0.63 (95% CI: 0.44-0.78) for the Kobayashi, Egami, Sano, Formosa, and Harada models, respectively. All 5 models showed low positive predictive values (0.14-0.39) and high negative predictive values (0.85-0.92). LIMITATIONS Potential differences in the characteristics of the target population among studies and lack of assessment of calibrations. CONCLUSIONS None of the 5 prediction models with external validation accurately distinguished between patients with and without IVIG resistance.
A systematic review on efficacy, safety and treatment durability of intravenous immunoglobulin in autoimmune bullous dermatoses: Special focus on indication and combination therapy
Experimental dermatology. 2023
Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of intravenous immunoglobulin (IVIg) as an alternative treatment should be explored to systematically review the available literature regarding treatment outcomes with IVIg in AIBD patients. The predefined search strategy was incorporated into the following database, MEDLINE/PubMed, Embase, Scopus and Web of Science on 18 July 2022. Sixty studies were enrolled using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The use of IVIg alone or combined with rituximab was reported in 500 patients with pemphigus, 82 patients with bullous pemphigoid, 146 patients with mucous membranes pemphigoid and 19 patients with epidermolysis bullosa acquisita. Disease remission with IVIg therapy and RTX + IVIg combination therapy were recorded as 82.8% and 86.7% in pemphigus, 88.0% and 100% in bullous pemphigoid and 91.3% and 75.0% in mucous membrane pemphigoid, respectively. In epidermolysis bullosa acquisita, treatment with IVIg led to 78.6% disease remission; no data were available regarding the treatment with RTX + IVIg in this group of patients. Among all the included patients, 37.5% experienced at least one IVIg-related side effect; the most common ones were headaches, fever/chills and nausea/vomiting. The use of IVIg with or without rituximab had a favourable clinical response in patients with AIBDs. IVIg has no major influence on the normal immune system, which makes its utilization for patients with AIBDs reasonable.
Treatment of immunoglobulin-resistant kawasaki disease: a Bayesian network meta-analysis of different regimens
Frontiers in pediatrics. 2023;11:1149519
BACKGROUND This study aimed to gather evidence from clinical trials on the efficacy and safety of the available treatments for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) in children. METHODS This work adopted the Newcastle-Ottawa scale to analyse the quality of the enrolled articles. A network meta-analysis was performed using clinical trials that compared drugs used to treat IVIG-resistant KD. Aggregate Data Drug Information System software v.1.16.5 was employed to analyse whether infliximab, second IVIG infusions, and intravenous pulse methylprednisolone (IVMP) were safe and effective. RESULTS Ten studies, involving 704 patients with IVIG-resistant KD, were identified and analysed. Overall, infliximab exhibited remarkable antipyretic activity compared with the second IVIG infusions (2.46, 1.00-6.94). According to the drug rank, infliximab was the best option against IVIG-resistant KD. Regarding adverse effects, the infliximab group was more prone to hepatomegaly. A second IVIG infusion was more likely to result in haemolytic anaemia. IVMP treatment was more susceptible to bradycardia, hyperglycaemia, hypertension, and hypothermia. In addition, infliximab, IVMP, and the second IVIG infusions showed no significant differences in the risk of developing a coronary artery aneurysm (CAA). CONCLUSION Infliximab was the best option against IVIG-resistant KD, and IVMP, infliximab, and second IVIG infusions have not significant differences of prevent CAA in patients with IVIG-resistant KD. SYSTEMATIC REVIEW REGISTRATION Identifier: https://osf.io/3894y.
The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis
Italian journal of pediatrics. 2023;49(1):45
BACKGROUND The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients. METHODS We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1-2 months of follow-up. RESULTS 27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50-2.15; Pâ€‰<â€‰.00001; I(2)â€‰=â€‰75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40-0.80; Pâ€‰=â€‰.001; I(2)â€‰=â€‰76%). There was a lower risk of CALs during 1-2 months follow-up for those who started IVIG administration within 10 days from the onset. CONCLUSIONS Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.
Intravenous immunoglobulin for the treatment of Kawasaki disease
The Cochrane Database of Systematic Reviews. 2023;1(1):Cd014884
BACKGROUND Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary artery abnormalities (CAAs). The primary treatment is intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA/aspirin), with doses and regimens differing between institutions. It is important to know which regimens are the safest and most effective in preventing complications. OBJECTIVES To evaluate the efficacy and safety of IVIG in treating and preventing cardiac consequences of Kawasaki disease. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 April 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) investigating the use of IVIG for the treatment of KD. We included studies involving treatment for initial or refractory KD, or both. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were incidence of CAAs and incidence of any adverse effects after treatment. Our secondary outcomes were acute coronary syndromes, duration of fever, need for additional treatment, length of hospital stay, and mortality. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS We identified 31 RCTs involving a total of 4609 participants with KD. Studies compared IVIG with ASA, another dose or regimen of IVIG, prednisolone, or infliximab. The majority of studies reported on primary treatment, so those results are reported below. A limited number of studies investigated secondary or tertiary treatment in IVIG-resistant patients. Doses and regimens of IVIG infusion varied between studies, and all studies had some concerns related to risk of bias. Primary treatment with IVIG compared to ASA for people with KD Compared to ASA treatment, IVIG probably reduces the incidence of CAAs in people with KD up to 30 days (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41 to 0.87; 11 studies, 1437 participants; moderate-certainty evidence). The individual studies reported a range of adverse effects, but there was little to no difference in numbers of adverse effects between treatment groups (OR 0.57, 95% CI 0.17 to 1.89; 10 studies, 1376 participants; very low-certainty evidence). There was limited evidence for the incidence of acute coronary syndromes, so we are uncertain of any effects. Duration of fever days from treatment onset was probably shorter in the IVIG group (mean difference (MD) -4.00 days, 95% CI -5.06 to -2.93; 3 studies, 307 participants; moderate-certainty evidence). There was little or no difference between groups in need for additional treatment (OR 0.27, 95% CI 0.05 to 1.57; 3 studies, 272 participants; low-certainty evidence). No study reported length of hospital stay, and no deaths were reported in either group. Primary treatment with IVIG compared to different infusion regimens of IVIG for people with KD Higher-dose regimens of IVIG probably reduce the incidence of CAAs compared to medium- or lower-dose regimens of IVIG up to 30 days (OR 0.60, 95% CI 0.40 to 0.89; 8 studies, 1824 participants; moderate-certainty evidence). There was little to no difference in the number of adverse effects between groups (OR 1.11, 95% CI 0.52 to 2.37; 6 studies, 1659 participants; low-certainty evidence). No study reported on acute coronary syndromes. Higher-dose IVIG may reduce the duration of fever compared to medium- or lower-dose regimens (MD -0.71 days, 95% CI -1.36 to -0.06; 4 studies, 992 participants; low-certainty evidence). Higher-dose regimens may reduce the need for additional treatment (OR 0.29, 95% CI 0.10 to 0.88; 4 studies, 1125 participants; low-certainty evidence). We did not detect a clear difference in length of hospital stay between infusion regimens (MD -0.24, 95% CI -0.78 to 0.30; 3 studies, 752 participants; low-certainty evidence). One study reported mortality, and there was little to no difference detected between regimens (moderate-certainty evidence). Primary treatment with IVIG compared to prednisolone for people with KD The evidence comparing IVIG with prednisolone on incidence of CAA is very uncertain (OR 0.60, 95% CI 0.24 to 1.48; 2 studies, 140 participants; very low-certainty evidence), and there was little to no difference between groups in adverse effects (OR 4.18, 95% CI 0.19 to 89.48; 1 study; 90 participants; low-certainty evidence). We are very uncertain of the impact on duration of fever, as two studies reported this outcome differently and showed conflicting results. One study reported on acute coronary syndromes and mortality, finding little or no difference between groups (low-certainty evidence). No study reported the need for additional treatment or length of hospital stay. AUTHORS' CONCLUSIONS The included RCTs investigated a variety of comparisons, and the small number of events observed during the study periods limited detection of effects. The certainty of the evidence ranged from moderate to very low due to concerns related to risk of bias, imprecision, and inconsistency. The available evidence indicated that high-dose IVIG regimens are probably associated with a reduced risk of CAA formation compared to ASA or medium- or low-dose IVIG regimens. There were no clinically significant differences in incidence of adverse effects, which suggests there is little concern about the safety of IVIG. Compared to ASA, high-dose IVIG probably reduced the duration of fever, but there was little or no difference detected in the need for additional treatment. Compared to medium- or low-dose IVIG, there may be reduced duration of fever and reduced need for additional treatment. We were unable to draw any conclusions regarding acute coronary syndromes, mortality, or length of hospital stay, or for the comparison IVIG versus prednisolone. Our findings are in keeping with current guideline recommendations and evidence from long-term epidemiology studies.
Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled trials
BACKGROUND Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD. METHODS An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100-400 mg), medium (1 g), and high (at least 2 g). FINDINGS A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=-1.76 days (95% confidence intervals (95% CIs): -3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18-1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00-0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00-1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07-0.62) in refractory-stage KD. INTERPRETATION The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results. FUNDING None.
The Therapeutic Efficacy and Safety of Intravenous Immunoglobulin in Dermatomyositis and Polymyositis: A Systematic Review and Meta-Analysis
Modern rheumatology. 2022
OBJECTIVES To evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of dermatomyositis (DM) and polymyositis (PM). METHODS A comprehensive systematic review was conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews And Meta-analyses). PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched to find articles published between July 1919 and May 2021 concerning IVIG therapy in PM/DM. We analyzed continuum data through mean difference and the estimated pooled improvement rate through Log transformation. We calculated all the effect measures with a 95% confidence interval. The I²statistic was calculated to assess statistical heterogeneity across the studies. I²values of 25%, 50% and 75% were defined as low, moderate and high, respectively. All analyses were conducted using R Studio, Version 3.6.3. RESULTS Seventeen papers pertinent to our questions were found: three case-control studies, fourteen non-randomized studies. We evaluated the efficacy of IVIG in DM/PM by the indicators of creatine kinase (CK), Manual Muscle Test (MMT) scores, Medical Research Council (MRC) scale, the Activities of Daily Living (ADL) scale and the pooled improvement rate. In a meta-analysis, we found that IVIG significantly improved the level of CK (SMD -0.69, 95%CI -0.93, -0.46; P<0.0001), MMT (SMD 1.12; 95%CI 0.77, 1.47; P<0.00001), MRC (SMD 1.59; 95%CI 0.86, 2.33; P<0.00001), ADL (SMD 1.07; 95%CI 0.59, 1.56; P<0.0001). The CK levels in DM and PM were also significantly improved after IVIG (SMD = -0.73, 95%CI -1.12, -0.34; P=0.0002; and SMD = -3.29, 95%CI -5.82, -0.76; P < 0.0001, respectively). The meta-analysis of three RCTs showed that there was a statistically significant improvement after IVIG (SMD 0.63; 95%CI 0.22, 1.03; P=0.002). In a random effects model pooled muscle power improvement rate was 77% (95% CI: 66.0-87.0%). Meta-analyses of IVIG as first-line therapy showed a significant improvement of CK level (SMD -0.71; 95%CI -1.12, -0.30; P=0.0007). In three studies, the polled improvement rate of esophageal disorders was 88% (95% CI: 80.0-95.0%). There was no statistically significant difference in the rate of improvement between the number of courses < 2 and ≥ 2 (0.80 vs. 0.80 %, P = 0.9). The corticosteroid-sparing effect of IVIG was also well demonstrated, with the proportion of corticosteroid-sparing success reaching 81.8% (72/88). Adverse reactions included headache, fever, Hypotension and dizzy and so on. Mild cortical stroke, staphylococcal septicaemia, asymptomatic myocardial infarction, cerebral infarction, deep vein thrombosis and subendocardial ischemia as severe adverse events were found in seven cases. CONCLUSION IVIG seems to be an effective drug for DM\PM, improving muscle strength, CK levels and esophageal involvement, and it is well tolerated by patients.
Characteristics, treatment, and outcomes of Myasthenia Gravis in COVID-19 patients: A systematic review
Clinical Neurology and Neurosurgery. 2022;213:107140
OBJECTIVE Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We performed a systematic review of the relevant literature with a key aim to assess the outcomes of invasive ventilation, mortality, and hospital length of stay (HLoS) for patients presenting with MG and COVID-19. METHODS We searched the PubMed, Scopus, Web of Science, and MedRxiv databases for original articles that reported patients with MG and COVID-19. We included all clinical studies that reported MG in patients with confirmed COVID-19 cases via RT-PCR tests. We collected data on patient background characteristics, symptoms, time between MG and COVID-19 diagnosis, MG and COVID-19 treatments, HLoS, and mortality at last available follow-up. We reported summary statistics as counts and percentages or mean±SD. When necessary, inverse variance weighting was used to aggregate patient-level data and summary statistics. RESULTS Nineteen studies with 152 patients (mean age 54.4 ± 12.7 years; 79/152 [52.0%] female) were included. Hypertension (62/141, 44.0%) and diabetes (30/141, 21.3%) were the most common comorbidities. The mean time between the diagnosis of MG and COVID-19 was7.0 ± 6.3 years. Diagnosis of COVID-19 was confirmed in all patients via RT-PCR tests. Fever (40/59, 67.8%) and ptosis (9/55, 16.4%) were the most frequent COVID-19 and MG symptoms, respectively. Azithromycin and ceftriaxone were the most common COVID-19 treatments, while prednisone and intravenous immunoglobulin were the most common MG treatments. Invasive ventilation treatment was required for 25/59 (42.4%) of patients. The mean HLoS was 18.2 ± 9.9 days. The mortality rate was 18/152 (11.8%). CONCLUSION This report provides an overview of the characteristics, treatment, and outcomes of MG in COVID-19 patients. Although COVID-19 may exaggerate the neurological symptoms and worsens the outcome in MG patients, we did not find enough evidence to support this notion. Further studies with larger numbers of patients with MG and COVID-19 are needed to better assess the clinical outcomes in these patients.
Immunoglobulin for multifocal motor neuropathy
The Cochrane database of systematic reviews. 2022;1(1):Cd004429
BACKGROUND Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few. People with MMN do not usually respond to steroids or plasma exchange. Uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin (IVIg). This is an update of a Cochrane Review first published in 2005, with an amendment in 2007. We updated the review to incorporate new evidence. OBJECTIVES To assess the efficacy and safety of intravenous and subcutaneous immunoglobulin in people with MMN. SEARCH METHODS We searched the following databases on 20 April 2021: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP for randomised controlled trials (RCTs) and quasi-RCTs, and checked the reference lists of included studies. SELECTION CRITERIA We considered RCTs and quasi-RCTs examining the effects of any dose of IVIg and subcutaneous immunoglobulin (SCIg) in people with definite or probable MMN for inclusion in the review. Eligible studies had to have measured at least one of the following outcomes: disability, muscle strength, or electrophysiological conduction block. We used studies that reported the frequency of adverse effects to assess safety. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed the literature searches to identify potentially relevant trials, assessed risk of bias of included studies, and extracted data. We followed standard Cochrane methodology. MAIN RESULTS Six cross-over RCTs including a total of 90 participants were suitable for inclusion in the review. Five RCTs compared IVIg to placebo, and one compared IVIg to SCIg. Four of the trials comparing IVIg versus placebo involved IVIg-naive participants (induction treatment). In the other two trials, participants were known IVIg responders receiving maintencance IVIg at baseline and were then randomised to maintenance treatment with IVIg or placebo in one trial, and IVIg or SCIg in the other. Risk of bias was variable in the included studies, with three studies at high risk of bias in at least one risk of bias domain. IVIg versus placebo (induction treatment): three RCTs including IVIg-naive participants reported a disability measure. Disability improved in seven out of 18 (39%) participants after IVIg treatment and in two out of 18 (11%) participants after placebo (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.89 to 10.12; 3 RCTs, 18 participants; low-certainty evidence). The proportion of participants with an improvement in disability at 12 months was not reported. Strength improved in 21 out of 27 (78%) IVIg-naive participants treated with IVIg and one out of 27 (4%) participants who received placebo (RR 11.00, 95% CI 2.86 to 42.25; 3 RCTs, 27 participants; low-certainty evidence). IVIg treatment may increase the proportion of people with resolution of at least one conduction block; however, the results were also consistent with no effect (RR 7.00, 95% CI 0.95 to 51.70; 4 RCTs, 28 participants; low-certainty evidence). IVIg versus placebo (maintenance treatment): a trial that included participants on maintenance IVIg treatment reported an increase in disability in 17 out of 42 (40%) people switching to placebo and seven out of 42 (17%) remaining on IVIg (RR 2.43, 95% CI 1.13 to 5.24; 1 RCT, 42 participants; moderate-certainty evidence) and a decrease in grip strength in 20 out of 42 (48%) participants after a switch to placebo treatment compared to four out of 42 (10%) remaining on IVIg (RR 0.20, 95% CI 0.07 to 0.54; 1 RCT, 42 participants; moderate-certainty evidence). Adverse events, IVIg versus placebo (induction or maintenance): four trials comparing IVIg and placebo reported adverse events, of which data from two studies could be meta-analysed. Transient side effects were reported in 71% of IVIg-treated participants versus 4.8% of placebo-treated participants in these studies. The pooled RR for the development of side effects was 10.33 (95% CI 2.15 to 49.77; 2 RCTs, 21 participants; very low-certainty evidence). There was only one serious side effect (pulmonary embolism) during IVIg treatment. IVIg versus SCIg (maintenance treatment): the trial that compared continuation of IVIg maintenance versus SCIg maintenance did not measure disability. The evidence was very uncertain for muscle strength (standardised mean difference 0.08, 95% CI -0.84 to 1.00; 1 RCT, 9 participants; very low-certainty evidence). The evidence was very uncertain for the number of people with side effects attributable to treatment (RR 0.50, 95% CI 0.18 to 1.40; 1 RCT, 9 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS Low-certainty evidence from three small RCTs shows that IVIg may improve muscle strength in people with MMN, and low-certainty evidence indicates that it may improve disability; the estimate of the magnitude of improvement of disability has wide CIs and needs further studies to secure its significance. Based on moderate-certainty evidence, it is probable that most IVIg responders deteriorate in disability and muscle strength after IVIg withdrawal. SCIg might be an alternative treatment to IVIg, but the evidence is very uncertain. More research is needed to identify people in whom IVIg withdrawal is possible and to confirm efficacy of SCIg as an alternative maintenance treatment.