Dataset Information

A meta-analysis on allergen-specific immunotherapy using MCT^® (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis.

ABSTRACT:

Background

The World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product-specific meta-analyses for allergen-specific immunotherapies because of the high degree of heterogeneity between individual products. This meta-analysis evaluates the efficacy and safety of Glutaraldehyde-modified and MCT^® (MicroCrystalline Tyrosine)-adsorbed allergoids (MATA).

Methods

The databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I² index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status.

Results

Eight randomized double-blind placebo-controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of -0.8 (CI: -1.24, -0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (-1.2 [CI: -2.11, -0.29]) and the total medication score (-2.2 [CI: -3.65, -0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population.

Conclusions

This meta-analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti-allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population.

SUBMITTER: Becker S

PROVIDER: S-EPMC8174800 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible.MethodsWe performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo.ResultsTwenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast.ConclusionsIn an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.

Project description:BACKGROUND:Mugwort pollen allergens represent the main cause of pollinosis in late summer. The major allergen, Art v 1, contains only one single immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36 also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36 -specific T cell receptors can be activated by HLA-DR4 molecules. To understand the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in HLA/peptide-binding and TCR-recognition, we investigated the molecular background of Art v 125-36 /MHC/TCR interactions in the context of HLA-DR1 compared to -DR4. RESULTS:The majority of Art v 125-36 -specific T cell lines and clones from HLA-DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally processed Art v 1-peptides when presented by HLA-DR1 or HLA-DR4 expressing antigen presenting cells. However, at limiting peptide concentrations DR1 was more effective in T cell stimulation. In addition, the minimal epitope for 50% of Art v 125-36 -specific T cells was shorter for DR1 than for DR4. In vitro binding assays of Art v 125-36 mutant peptides to isolated DR1- and DR4-molecules indicated similar binding capacities and use of the same register. In silico simulation of Art v 125-36 binding to HLA-DR1 and -DR4 suggested similar binding of the central part of the peptide to either molecule, but a higher flexibility of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1. CONCLUSIONS:The predominance of HLA-DR1 in the response to Art v 125-36 may be explained by subtle conformation changes of the peptide bound to DR1 compared to DR4. Computer simulation supported our experimental data by demonstrating differences in peptide mobility within the HLA-DR complex that may influence TCR-binding. We suggest that the minor differences observed in vitro may be more relevant in the microenvironment in vivo, so that only presentation by HLA-DR1, but not -DR4 permits successful T cell activation.

Project description:Ragweed (Ambrosia spp.) is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia) poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by synthetic cytosine phosphate-guanosine oligodeoxynucleotides promises a new treatment paradigm that aims to modulate the immune response, but it has yet to be proven in clinical trials.

Dataset Information

A meta-analysis on allergen-specific immunotherapy using MCT^® (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis.

Background

Methods

Results

Conclusions

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

A meta-analysis on allergen-specific immunotherapy using MCT® (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A meta-analysis on allergen-specific immunotherapy using MCT^® (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis.