Immunotherapy: The Meta-Analyses. What have we Learned?
Department of Allergy and Respiratory Medicine, Imperial College, National Heart and Lung Institute, Royal Brompton and Harefield Trust, Dovehouse Street, London SW3 6LY, UK. Immunology and allergy clinics of North America
(Impact Factor: 1.82).
05/2011; 31(2):159-73, vii. DOI: 10.1016/j.iac.2011.02.002
Meta-analysis is a powerful tool for evaluating the efficacy of a therapeutic intervention, and has clearly demonstrated that specific allergen immunotherapy (SIT) is effective for treating allergic rhinitis and asthma. Future research needs to focus on specifying the most effective forms of SIT for specific populations and allergens, using validated clinical outcomes, studying long-term outcomes (particularly the potential disease-modifying effect of immunotherapy), and assessing outcomes regarding health economics. The safety profile of SIT should be evaluated using international guidelines and terminology, and needs to include high-quality surveillance data.
Available from: Antonino Musarra
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ABSTRACT: The role of allergen-specific immunotherapy in asthma (AIT) is still a matter of debate. Actually, many controlled clinical trials have proved efficacy and safety of AIT in asthma, and some published meta-analyses, despite some methodological weaknesses, have confirmed these findings, the most recent and convincing being a meta-analysis on injection AIT studies. For sublingual AIT evidences do exist, but SLIT meta-analyses are mostly questioned due to some biases and inconsistencies. Most of these arise from methodological problems in single studies, usually small, underpowered and carried out with mixed populations. The main need, therefore, is to perform AIT clinical studies only in patients with asthma and following standardized protocols, as recommended by international Guidelines. Studies of AIT in asthma should also focus more on the long term and preventive effects of the treatment, rather than considering only the immediate efficacy on allergic symptoms. Furthermore, specific asthma features, such as lung function, bronchial reactivity, asthma control and exacerbations, should be included among the study outcomes.
European annals of allergy and clinical immunology 08/2011; 43(4):103-10.
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ABSTRACT: To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective.
To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response.
Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.
Current Opinion in Allergy and Clinical Immunology 12/2011; 11(6):571-8. DOI:10.1097/ACI.0b013e32834cbaab · 3.57 Impact Factor
Available from: Ulugbek Nurmatov
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ABSTRACT: Peanut allergy is one of the most common forms of food allergy encountered in clinical practice. In most cases, it does not spontaneously resolve; furthermore, it is frequently implicated in acute life-threatening reactions. The current management of peanut allergy centres on meticulous avoidance of peanuts and peanut-containing foods. Allergen-specific oral immunotherapy (OIT) for peanut allergy aims to induce desensitisation and then tolerance to peanut, and has the potential to revolutionise the management of peanut allergy. However, at present there is still considerable uncertainty about the effectiveness and safety of this approach.
To establish the effectiveness and safety of OIT in people with IgE-mediated peanut allergy who develop symptoms after peanut ingestion.
We searched in the following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE, Global Health, Google Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE, PakMediNet and TRIP. We also searched registers of on-going and unpublished trials. The date of the most recent search was January 2012.
Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials involving children or adults with clinical features indicative of IgE-mediated peanut allergy treated with allergen-specific OIT, compared with control group receiving either placebo or no treatment, were eligible for inclusion.
Two review authors independently checked and reviewed titles and abstracts of identified studies and assessed risk of bias. The full text of potentially relevant trials was assessed. Data extraction was independently performed by two reviewers with disagreements resolved through discussion.
We found one small RCT, judged to be at low risk of bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation to peanut and a clinical history of reaction to peanut within 60 minutes of exposure. The study did not include children who had moderate to severe asthma or who had a history of severe peanut anaphylaxis. Randomisation was in a 2:1 ratio resulting in 19 children being randomised to the intervention arm and nine to the placebo arm. Intervention arm children received OIT with peanut flour and control arm participants received placebo comprising of oat flour. The primary outcome was assessed using a double-blind, placebo controlled oral food challenge (OFC) at approximately one year. No data were available on longer term outcomes beyond the OFC conducted at the end of the study.Because of adverse events, three patients withdrew from the intervention arm before the completion of the study. Therefore, only 16 participants received the full course of peanut OIT, whereas all nine patients receiving placebo completed the trial. The per-protocol analysis found a significant increase in the threshold dose of peanut allergen required to trigger a reaction in those in the intervention arm with all 16 participants able to ingest the maximum cumulative dose of 5000 mg of peanut protein (which the authors equate as being equivalent to approximately 20 peanuts) without developing symptoms, whereas in the placebo group they were able to ingest a median cumulative dose of 280 mg (range: 0 to 1900 mg, P < 0.001) before experiencing symptoms. Per-protocol analyses also demonstrated that peanut OIT resulted in reductions in skin prick test size (P < 0.001), interleukin-5 (P = 0.01), interleukin-13 (P = 0.02) and an increase in peanut-specific immunoglobulin G(4) (IgG(4)) (P < 0.01).Children in the intervention arm experienced more adverse events during treatment than those in the placebo arm. In the initial day escalation phase, nine (47%) of the 19 participants initially enrolled in the OIT arm experienced clinically-relevant adverse events which required treatment with H(1)-antihistamines, two of which required additional treatment with epinephrine (adrenaline).
The one small RCT we found showed that allergen-specific peanut OIT can result in desensitisation in children, and that this is associated with evidence of underlying immune-modulation. However, this treatment approach was associated with a substantial risk of adverse events, although the majority of these were mild. In view of the risk of adverse events and the lack of evidence of long-term benefits, allergen-specific peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-mediated peanut allergy. Larger RCTs are needed to investigate the acceptability, long-term effectiveness and cost-effectiveness of safer treatment regimens, particularly in relation to the induction of clinical and immunological tolerance.
Cochrane database of systematic reviews (Online) 09/2012; 9(9):CD009014. DOI:10.1002/14651858.CD009014.pub2 · 6.03 Impact Factor
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