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Rheumatology (Oxford, England) Oct 2019The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the prevalence of ADAbs in JIA studies; investigate the effect of ADAbs on treatment efficacy and adverse events; and explore the effect of immunosuppressive therapy on antibody formation.
METHODS
PubMed, Embase and the Cochrane Library were systematically searched to identify relevant clinical trials and observational studies that reported prevalence of ADAbs. Studies were systematically reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses and appropriate proportional and pairwise meta-analyses were performed.
RESULTS
A total of 5183 references were screened; 28 articles, involving 26 studies and 2354 JIA patients, met eligibility criteria. Prevalence of ADAbs ranged from 0% to 82% across nine biologic agents. Overall pooled prevalence of ADAbs was 16.9% (95% CI, 9.5, 25.9). Qualitative analysis of included studies indicated that antibodies to infliximab, adalimumab, anakinra and tocilizumab were associated with treatment failure and/or hypersensitivity reactions. Concomitant MTX uniformly reduced the risk of antibody formation during adalimumab treatment (risk ratio 0.33; 95% CI 0.21, 0.52).
CONCLUSION
The association of ADAbs with treatment failure and hypersensitivity reactions indicates their clinical relevance in paediatric patients with JIA. Based on our findings, we recommend a preliminary course of action regarding immunogenicity of biologic agents in patients with JIA. Further strategies to predict, prevent, detect and manage immunogenicity could optimize treatment outcomes and personalize treatment with biologic therapies.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antibody Formation; Antirheumatic Agents; Arthritis, Juvenile; Biological Factors; Child; Clinical Trials as Topic; Humans; Infliximab; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Observational Studies as Topic
PubMed: 30809664
DOI: 10.1093/rheumatology/kez030 -
The Journal of Infectious Diseases Apr 2019A number of enhanced influenza vaccines have been developed for use in older adults, including high-dose, MF59-adjuvanted, and intradermal vaccines. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
A number of enhanced influenza vaccines have been developed for use in older adults, including high-dose, MF59-adjuvanted, and intradermal vaccines.
METHODS
We conducted a systematic review examining the improvements in antibody responses measured by the hemagglutination inhibition assay associated with these enhanced vaccines, compared with each other and with the standard-dose (SD) vaccine using random effects models.
RESULTS
Thirty-nine trials were included. Compared with adults aged ≥60 years receiving SD vaccines, those receiving enhanced vaccines had significantly higher postvaccination titers (for all vaccine strains) and higher proportions with elevated titers ≥40 (for most vaccine strains). High-dose vaccine elicited 82% higher postvaccination titer to A(H3N2) compared with SD vaccine; this was significantly higher than the 52% estimated for MF59-adjuvanted versus SD vaccines (P = .04), which was higher than the 32% estimated for intradermal versus SD vaccines (P < .01).
CONCLUSIONS
Overall, by summarizing current evidence, we found that enhanced vaccines had greater antibody responses than the SD vaccine. Indications of differences among enhanced vaccines highlight the fact that further research is needed to compare new vaccine options, especially during seasons with mismatched circulating strains and for immune outcomes other than hemagglutination inhibition titers as well as vaccine efficacy.
Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Aging; Antibody Formation; Hemagglutination Inhibition Tests; Humans; Immunogenicity, Vaccine; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Influenza Vaccines; Influenza, Human; Injections, Intradermal; Middle Aged
PubMed: 30551178
DOI: 10.1093/infdis/jiy720 -
CNS Neuroscience & Therapeutics Feb 2019Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy...
AIMS
Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body dementia with (LBD), remains exceedingly low. The present work overviews the most influential research literature collected on MEDLINE, ISI Web of Science, Cochrane Library, and Scopus for available treatment in atypical parkinsonisms without time restriction.
DISCUSSION
Transdermal rotigotine, autologous mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil, rivastigmine, memantine, and the deep brain stimulation have shown some benefits in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation inhibition, cell replacement, selective serotonin reuptake inhibitor, active immunization, inhibition of toxic α-synuclein oligomers formation, and inhibition of microglia.
CONCLUSION
A detailed knowledge of the pathological mechanism underlying the disorders is needed, and disease-modifying therapies are required to offer better therapeutic options to physician and caregivers of APS patients.
Topics: Adult; Aged; Antiparkinson Agents; Child; Humans; Parkinsonian Disorders
PubMed: 30294976
DOI: 10.1111/cns.13068 -
Drug Design, Development and Therapy 2018Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially... (Meta-Analysis)
Meta-Analysis Review
The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially in the elderly. Probiotics are live microorganisms with immunomodulatory effects and may enhance the immune responses to influenza vaccination.
METHODS
We conducted a systematic review and meta-analysis to determine the influence of prebiotics/probiotics/synbiotics supplementation on vaccine responses to influenza vaccination. Studies were systematically identified from electronic databases up to July 2017. Information regarding study population, influenza vaccination, components of supplements, and immune responses were extracted and analyzed. Twelve studies, investigating a total of 688 participants, were included in this review.
RESULTS
Patients with prebiotics/probiotics supplements were found to have higher influenza hemagglutination inhibition antibody titers after vaccination (for A/H1N1, 42.89 vs 35.76, mean difference =7.14, 95% CI =2.73, 11.55, =0.002; for A/H3N2, 105.4 vs 88.25, mean difference =17.19, 95% CI =3.39, 30.99, =0.01; for B strain, 34.87 vs 30.73, mean difference =4.17, 95% CI =0.37, 7.96, =0.03).
CONCLUSION
Supplementation with prebiotics or probiotics may enhance the influenza hemagglutination inhibition antibody titers in all A/H1N1, A/H3N2, and B strains (20%, 19.5%, and 13.6% increases, respectively). Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted.
Topics: Antibodies, Viral; Antibody Formation; Dietary Supplements; Humans; Influenza Vaccines; Influenza, Human; Prebiotics; Probiotics; Randomized Controlled Trials as Topic
PubMed: 29416317
DOI: 10.2147/DDDT.S155110 -
BioDrugs : Clinical Immunotherapeutics,... Aug 2017A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.
METHODS
Literature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn's disease, and ulcerative colitis.
RESULTS
Of >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0-83%), adalimumab (0-54%), and infliximab biosimilar CT-P13 (21-52%), and the lowest with secukinumab (0-1%), ustekinumab (1-11%), etanercept (0-13%), and golimumab (0-19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb- patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases.
CONCLUSIONS
Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.
Topics: Abatacept; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Juvenile; Arthritis, Psoriatic; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Colitis, Ulcerative; Crohn Disease; Etanercept; Humans; Infliximab; Spondylitis, Ankylosing; Ustekinumab
PubMed: 28612180
DOI: 10.1007/s40259-017-0231-8 -
PloS One 2017Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our... (Review)
Review
BACKGROUND
Multiple inducers of in vitro Neutrophil Extracellular Trap (NET) formation (NETosis) have been described. Since there is much variation in study design and results, our aim was to create a systematic review of NETosis inducers and perform a standardized in vitro study of NETosis inducers important in (cardiac) wound healing.
METHODS
In vitro NETosis was studied by incubating neutrophils with PMA, living and dead bacteria (S. aureus and E. coli), LPS, (activated) platelets (supernatant), glucose and calcium ionophore Ionomycin using 3-hour periods of time-lapse confocal imaging.
RESULTS
PMA is a consistent and potent inducer of NETosis. Ionomycin also consistently resulted in extrusion of DNA, albeit with a process that differs from the NETosis process induced by PMA. In our standardized experiments, living bacteria were also potent inducers of NETosis, but dead bacteria, LPS, (activated) platelets (supernatant) and glucose did not induce NETosis.
CONCLUSION
Our systematic review confirms that there is much variation in study design and results of NETosis induction. Our experimental results confirm that under standardized conditions, PMA, living bacteria and Ionomycin all strongly induce NETosis, but real-time confocal imaging reveal different courses of events.
Topics: Escherichia coli; Extracellular Traps; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Myocardium; Staphylococcus aureus; Wound Healing
PubMed: 28486563
DOI: 10.1371/journal.pone.0176472 -
Vaccine Jan 2017The influenza vaccine is less immunogenic in older than younger adults, and the duration of protection is unclear. Determining if protection persists beyond a typical... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The influenza vaccine is less immunogenic in older than younger adults, and the duration of protection is unclear. Determining if protection persists beyond a typical seasonal epidemic is important for climates where influenza virus activity is year-round.
METHODS
A systematic review protocol was developed and registered with PROSPERO [CRD42015023847]. Electronic databases were searched systematically for studies reporting haemagglutination-inhibition (HI) titres 180-360days following vaccination with inactivated trivalent seasonal influenza vaccine, in adults aged ⩾65years. Geometric mean titre (GMT) and seroprotection (HI titre ⩾1:40) at each time point was extracted. A Bayesian model was developed of titre trajectories from pre-vaccination to Day 360. In the meta-analysis, studies were aggregated using a random-effects model to compare pre-vaccination with post-vaccination HI titres at Day 21-42 ('seroconversion'), Day 180 and Day 360. Potential sources of bias were systematically assessed, and heterogeneity explored.
RESULTS
2864 articles were identified in the literature search, of which nineteen met study inclusion/exclusion criteria. Sixteen studies contained analysable data from 2565 subjects. In the Bayesian model, the proportion of subjects seroprotected increased from 41-51% pre-vaccination to 75-78% at seroconversion. Seroprotection subsequently fell below 60% for all serotypes by Day 360: A/H1 42% (95% CI 38-46), A/H3 59% (54-63), B 47% (42-52). The Bayesian model of GMT trajectories revealed a similar pattern. By Day 360, titres were similar to pre-vaccination levels. In the meta-analysis, no significant difference in proportion of subjects seroprotected, 0 (-0.11, 0.11) or in logGMT 0.30 (-0.02, 0.63) was identified by Day 360 compared with pre-vaccination. The quality of this evidence was limited to moderate on account of significant participant dropout.
CONCLUSIONS
The review found consistent evidence that HI antibody responses following influenza vaccination do not reliably persist year-round in older adults. Alternative vaccination strategies could provide clinical benefits in regions where year-round protection is important.
Topics: Aged; Aged, 80 and over; Antibodies, Viral; Antibody Formation; Hemagglutination Inhibition Tests; Humans; Influenza Vaccines; Orthomyxoviridae; Time Factors
PubMed: 27939013
DOI: 10.1016/j.vaccine.2016.11.013 -
The Journal of Infection Jan 2015Cyclical fluctuations in host immunity have been proposed as a driver of respiratory infection seasonality, however few studies have attempted to directly assess whether... (Review)
Review
INTRODUCTION
Cyclical fluctuations in host immunity have been proposed as a driver of respiratory infection seasonality, however few studies have attempted to directly assess whether or not seasonal immune modulation occurs in humans.
MATERIALS AND METHODS
We reviewed studies assessing immune status at different times of the year, restricting our review to studies assessing any of the following three biomarkers: antibody responses following vaccination, delayed-type hypersensitivity responses following skin testing, and clinical responses following experimental infection.
RESULTS
After systematic review and critical appraisal of the literature, six separate studies were available for final discussion. These results indicate that human immunity does vary by season. In the tropical setting of West Africa, both cell mediated and humoral immune responses appear to be reduced in children during the rainy season. In the tropical setting of Bangladesh, cell mediated immune responses also appear to be reduced in children during the rainy season. In the temperate setting of Russia, resistance to influenza infection appears to be reduced in young adults during winter.
CONCLUSIONS
Seasonal variation in immunity appears to occur in humans, and it is plausible that this variation may contribute to the seasonality of respiratory infections. Further research to assess the extent of seasonal immune modulation is required. We outline a number of recommendations to minimise bias in future studies.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antibody Formation; Biomarkers; Child; Child, Preschool; Environment; Female; Humans; Hypersensitivity, Delayed; Immune System Phenomena; Infant; Infant, Newborn; Male; Middle Aged; Rain; Seasons; Sex Factors; Skin Tests; Tropical Climate; Vaccines; Young Adult
PubMed: 25246360
DOI: 10.1016/j.jinf.2014.09.006