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The Cochrane Database of Systematic... Jan 2022Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with... (Review)
Review
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.
Topics: Humans; Immunoglobulins, Intravenous; Plasma Exchange; Polyneuropathies; Randomized Controlled Trials as Topic
PubMed: 35015296
DOI: 10.1002/14651858.CD004429.pub3 -
RMD Open Dec 2023Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing...
OBJECTIVE
Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing reported data on the CD38-targeting antibody daratumumab as a new therapeutic approach in autoantibody-mediated autoimmune diseases.
METHODS
A protocolised systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases (Medline and Embase) were searched for suitable studies. Usage of daratumumab in non-oncological or non-transplantation associated diseases with autoimmune pathophysiology was analysed including patient characteristics, therapeutic regimen, adverse events and patient outcome.
RESULTS
38 publications reporting the clinical course of 83 patients met the inclusion criteria. Daratumumab usage was reported in therapy-refractory cases (median of 5 different previous therapies) in 24 different autoimmune diseases. The median number of applications of daratumumab was 4, mainly via intravenous applications (87%). Concomitant treatment included glucocorticoids in 64% of patients, intravenous immunoglobulins (33%) and rituximab (17%). Remission or improvement of disease was reported in 81% of patients. Autoantibody depletion or reduction was stated in 52% of patients. Death occurred in three patients (3%). Adverse events were reported in 45% of patients including application-associated reaction (20%), infection (19%) and hypogammaglobulinaemia (33%).
CONCLUSION
Targeting CD38 via daratumumab is a new promising therapeutic option in therapy refractory autoimmune diseases. Efficacy as well as optimal therapeutic regimen and management or prevention of adverse events require further investigation. Therefore, systematic clinical trials of this therapeutic approach are needed.
Topics: Humans; Antibodies, Monoclonal; Rituximab; Autoimmune Diseases; Autoantibodies
PubMed: 38101819
DOI: 10.1136/rmdopen-2023-003604 -
Journal of Medical Virology Jul 2023Diverse clinical and laboratory features of multisystem inflammatory syndrome (MIS-C) have been reported in the literature. Despite the worldwide distribution, systemic... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis on the serological, immunological, and cardiac parameters of the multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 infection.
Diverse clinical and laboratory features of multisystem inflammatory syndrome (MIS-C) have been reported in the literature. Despite the worldwide distribution, systemic studies regarding the laboratory results do not exist. Therefore, we aimed to perform this systematic review and meta-analysis to evaluate the serological, immunological, and cardiac parameters of the MIS-C associated with SARS-CoV-2 infection. We searched the PubMed, Scopus, and Web of Science databases using specific keywords for any papers published in English since the disease onset and the first report until July 19, 2020. The inclusion criteria were children <21 years diagnosed with MIS-C without any limitation on defining criteria. Forty-eight studies were included in the final analysis, with a total population size of 3543 children with MIS-C. The median age of the included patients was 8.3 (6.7-9) years. The pooled prevalence of male patients was 59% (95% CI: 56%-61%) and 62% (95% CI: 55%-69%) were admitted in ICU. The pooled prevalence of positive SARS-CoV-2 RT-PCR, SARS-CoV-2 IgM, and SARS-CoV-2 IgG antibody tests was 33% (95% CI: 27%-40%), 39% (95% CI: 22%-58%) and 81% (95% CI: 76%-86%), respectively. The positivity rate of the inflammatory markers was as follows: CRP (96%, 95% CI: 90%-100%), d-dimer (87%, 95% CI: 81%-93%), ESR (81%, 95% CI: 74%-87%), procalcitonin (88%, 95% CI: 76%-97%), ferritin (79%, 95% CI: 69%-87%), and fibrinogen (77%, 95% CI: 70%-84%). The pooled prevalence of elevated brain natriuretic peptide (BNP) level, pro-BNP, and troponin were found in 60% (95% CI: 44%-75%), 87% (95% CI: 75%-96%), and 55% (95% CI: 45%-64%), respectively. The majority of patients had positive SARS-CoV-2 IgG test. Nearly one-third of the cases showed negative RT-PCR results. Cardiac and inflammatory markers were elevated in the majority of cases. These findings suggest that hyperinflammation and cardiac dysfunction are common complications of MIS-C.
Topics: Child; Humans; Male; Female; COVID-19; SARS-CoV-2; Immunoglobulin G; Hospitalization; Antibodies, Viral
PubMed: 37436781
DOI: 10.1002/jmv.28927 -
The Lancet. Microbe Nov 2023Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have not been identified. We aimed to assess how the dose and timing of administration affect treatment outcome.
METHODS
In this systematic review and meta-analysis, we extracted data from published studies of passive antibody treatment from Jan 1, 2019, to Jan 31, 2023, that were identified by searching multiple databases, including MEDLINE, PubMed, and ClinicalTrials.gov. We included only randomised controlled trials of passive antibody administration for the prevention or treatment of COVID-19. To compare administered antibody dose between different treatments, we used data on in-vitro neutralisation titres to normalise dose by antibody potency. We used mixed-effects regression and model fitting to analyse the relationship between timing, dose and efficacy.
FINDINGS
We found 58 randomised controlled trials that investigated passive antibody therapies for the treatment or prevention of COVID-19. Earlier clinical stage at treatment initiation was highly predictive of the efficacy of both monoclonal antibodies (p<0·0001) and convalescent plasma therapy (p=0·030) in preventing progression to subsequent stages, with either prophylaxis or treatment in outpatients showing the greatest effects. For the treatment of outpatients with COVID-19, we found a significant association between the dose administered and efficacy in preventing hospitalisation (relative risk 0·77; p<0·0001). Using this relationship, we predicted that no approved monoclonal antibody was expected to provide more than 30% efficacy against some omicron (B.1.1.529) subvariants, such as BQ.1.1.
INTERPRETATION
Early administration before hospitalisation and sufficient doses of passive antibody therapy are crucial to achieving high efficacy in preventing clinical progression. The relationship between dose and efficacy provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19.
FUNDING
The Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council, the University of New South Wales, Monash University, Haematology Society of Australia and New Zealand, Leukaemia Foundation, and the Victorian Government.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Serotherapy; Australia; Treatment Outcome; Antibodies, Monoclonal
PubMed: 37924835
DOI: 10.1016/S2666-5247(23)00194-5 -
International Immunopharmacology Apr 2023This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research. (Review)
Review
OBJECTIVE
This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research.
BACKGROUND
Migraine is a chronic neurovascular disorder that causes disability and a social burden. There are various medications used for migraine prevention regimens, most of which have unwanted side effects and aren't often quite effective. Erenumab is a monoclonal antibody that targets calcitonin gene-related peptide receptors and was recently approved by the Food and Drug Administration for migraine prevention.
METHODS
For this systematic review, we searched through Scopus and PubMed databases using "Erenumab" or "AMG 334" and "migraine" as keywords, and all the studies from 2016 to March 18, 2022, were included. Original English articles assessing any outcomes referring to the efficacy of Erenumab in migraine headache treatment were included in this study.
RESULTS
We found 53 out of 605 papers eligible to be investigated. Erenumab in both dosages of 70 mg and 140 mg could decrease the mean of monthly migraine days and monthly acute migraine-specific medication days. Erenumab also has a higher rate of ≥ 50 %, ≥ 75 %, and 100 % reduction in monthly migraine days from the baseline in different regions. The efficacy of Erenumab was initiated in the first week of administration and sustained throughout and after treatment. Erenumab was also potent in the treatment of migraine with allodynia, aura, prior preventive therapy failure, medication overuse headache, and menstrual migraine. Erenumab also had favorable outcomes in combination therapy with other preventive drugs like Onabotulinumtoxin-A.
CONCLUSION
Erenumab had remarkable efficacy in the short and long-term treatment of episodic and chronic migraine, notably the patients with difficult-to-treat migraine headaches.
Topics: Humans; Calcitonin Gene-Related Peptide Receptor Antagonists; Migraine Disorders; Antibodies, Monoclonal; Chronic Disease; Combined Modality Therapy
PubMed: 37012858
DOI: 10.1016/j.intimp.2022.109366 -
The Journal of Infectious Diseases Aug 2022Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of...
BACKGROUND
Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe.
METHODS
We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting.
RESULTS
A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency.
CONCLUSIONS
We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Hospitalization; Humans; Infant; Infant, Newborn; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 35333332
DOI: 10.1093/infdis/jiac059 -
Experimental Dermatology Jul 2023Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of... (Review)
Review
A systematic review on efficacy, safety and treatment durability of intravenous immunoglobulin in autoimmune bullous dermatoses: Special focus on indication and combination therapy.
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.
Topics: Humans; Pemphigoid, Bullous; Immunoglobulins, Intravenous; Epidermolysis Bullosa Acquisita; Pemphigus; Rituximab; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Benign Mucous Membrane
PubMed: 37150538
DOI: 10.1111/exd.14829 -
International Journal of... 2023Lecanemab is the latest monoclonal antibody that targets beta-amyloid approved exclusively for treatment of Alzheimer's disease with mild cognitive impairment or mild...
BACKGROUND
Lecanemab is the latest monoclonal antibody that targets beta-amyloid approved exclusively for treatment of Alzheimer's disease with mild cognitive impairment or mild dementia. This article aims to provide a systematic review of the efficacy, and safety of lecanemab in slowing clinical decline in Alzheimer's disease.
METHODS
A comprehensive search of various databases, including the National Institute of Health clinical trials registry, PubMed, and the Cochrane library, was conducted until July 2023 using the keywords lecanemab, BAN2401, and Alzheimer's disease. Additionally, conference abstracts listed in the Cochrane database (including Embase) and drug information from the US Food and Drug Administration (FDA) label were examined. Only clinical trials published in the English language were considered. In total, 107 articles were retrieved, and after thorough evaluation, three randomized, double-blind, multicenter clinical trials involving 2729 participants were included in the analysis.
RESULTS
The FDA approved lecanemab for Alzheimer's disease in January 2023 which acts as a novel disease-modifying anti-amyloid-beta (Aβ) human monoclonal antibody and is administered intravenously. Based on the clinical trials included in this review, lecanemab was found efficacious in reducing the accumulation of beta-amyloid and slowing down the cognitive decline and it was well tolerated. Lecanemab had a statistically significant change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer's Disease Composite Score (ADCOMS), Alzheimer's Disease Assessment Scale (ADAScog14), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), and reductions in brain amyloid burden. The most common treatment-emergent adverse events were headache, infusion-related reactions, and Amyloid related imaging abnormalities-edema.
CONCLUSIONS
Lecanemab therapy led to a substantial decrease in amyloid plaques and a noticeable slowing of clinical decline. The findings suggest a meaningful connection between the reduction in amyloid and the positive impact on patients' clinical outcomes, hinting at potential disease-modifying effects.
Topics: Humans; Alzheimer Disease; Activities of Daily Living; Amyloid beta-Peptides; Antibodies, Monoclonal; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37902139
DOI: 10.1177/03946320231209839 -
Acta Neurologica Belgica Dec 2023We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people with multiple sclerosis (MS).
METHODS
The four databases including PubMed, Scopus, Embase, and Web of Science were comprehensively searched in April 2022. We defined PICO as follows. Problem or study population (P): patients with MS; intervention (I): Rituximab; comparison (C): none; outcome (O): efficacy and safety.
RESULTS
After two-step screening, a total of 27 studies entered into our qualitative and quantitative synthesis. Our analysis showed a significant decrease in EDSS score in all patients with MS after treatment (SMD: - 0.44, 95% CI - 0.85, - 0.03). In addition, the ARR was reduced after using rituximab compared to the pre-treatment period (SMD: - 0.65, 95% CI - 1.55, 0.24) but it was not significant. The most common side effect after rituximab with a pooled prevalence of 28.63% (95% CI 16.61%, 42.33%). Furthermore, the pooled prevalence of infection was 24% in patients with MS (95% CI 13%, 36%). In the end, the pooled prevalence of malignancies after rituximab treatment was 0.39% (95% CI 0.02%, 1.03%).
CONCLUSION
Our findings illustrated an acceptable safety for this treatment. However, further studies with randomized design, long follow-up, and large sample sizes are needed to confirm the safety and efficacy of rituximab in patients with MS.
Topics: Humans; Rituximab; Multiple Sclerosis; Antibodies, Monoclonal
PubMed: 37428437
DOI: 10.1007/s13760-023-02329-4 -
Critical Reviews in Oncology/hematology Dec 2023The advent of targeted therapies signaled novel avenues for more optimal oncological outcomes. Antibody-drug conjugates (ADCs) have risen as a cornerstone of the... (Review)
Review
BACKGROUND
The advent of targeted therapies signaled novel avenues for more optimal oncological outcomes. Antibody-drug conjugates (ADCs) have risen as a cornerstone of the ever-expanding targeted therapy era. The purpose of this systematic review is to delineate the rapidly evolving clinical landscape of ADCs for solid tumors.
METHODS
A literature search was performed in Medline, Embase and Cochrane databases for phase II and III clinical trials. Outcomes of interest were the objective response rate, overall survival, progression-free survival and adverse events.
RESULTS
A total of 92 clinical trials (76 phase II and 16 phase III) evaluated the efficacy and safety of ADCs for a plethora of solid tumors. Out of the 30 investigated ADCs, 8 have received approval by regulatory organizations for solid tumors. Currently, 52 phase III clinical trials for ADCs are ongoing.
CONCLUSION
ADCs have shown promising results for several solid tumors and various cancer settings.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Neoplasms
PubMed: 37866413
DOI: 10.1016/j.critrevonc.2023.104189