Sangeeta Dhami

Cat allergy can manifest as allergic rhinitis, conjunctivitis and/or asthma. With widespread cat ownership and exposure, cat allergy has emerged as a major cause of morbidity. Cat allergen immunotherapy is a potential disease modifying treatment for patients with cat allergy. We examine evidence on the effectiveness, cost-effectiveness and safety of cat allergen immunotherapy and consider the clinical contexts in which it should be prescribed. The European Association of Allergy and Clinical Immunology systematic reviews on allergic rhinitis and asthma along with the accompanying guidelines on allergic rhinitis were used as primary sources of evidence. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are most common routes of administration for allergen immunotherapy (AIT). A limited number of high-quality studies related to cat dander have shown mixed results in improvements in ocular and nasal symptoms, asthma symptoms, peak expiratory flow rate and medication use scores with subcutaneous immunotherapy. Two studies examining cat dander and cat-related allergy response with sublingual immunotherapy have shown mixed results in terms of symptomatic response. One randomized trial examining intralymphatic immunotherapy has shown a positive symptom response and a favourable safety profile. Although studies have reported mixed results regarding safety of SCIT, adverse events have been reported more commonly with SCIT than SLIT. There is a limited body of high-quality evidence on the effectiveness and safety of cat AIT and no high-quality data on its cost-effectiveness. The available evidence on effectiveness is mixed based on studying a limited array of immunological, physiological and patient-reported outcome measures. Based on this evidence and extrapolating on the wider evidence base in AIT, it is likely that some patients may benefit from this modality of treatment, particularly those with moderate-to-severe disease who are inadequately controlled on allergen avoidance measures and pharmacotherapy and those who are monosensitized to Felix Domesticus 1. Further evidence is, however, required from larger trials before more definitive advice can be offered.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE‐mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost‐effectiveness of AIT for these conditions.Methods: We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations.Results: Twenty‐three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost‐effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost‐effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost‐effectiveness threshold of £20 000/quality‐adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost‐effective with an incremental cost‐effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost‐effective for very high‐risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost‐effectiveness of AIT for food allergy.Conclusions: Overall, the evidence to support the cost‐effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost‐effective for people with allergic rhinitis with or without asthma and in high‐risk subgroups for venom allergy. We were unable to draw any conclusions on the cost‐effectiveness of AIT for food allergy.

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC. We undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized. Our searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT. We found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews.

There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma. To undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma. We searched nine electronic databases from inception to October 31, 2015. Systematic reviews were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme quality assessment tool for systematic reviews. Data were descriptively and thematically synthesized. We identified nine eligible systematic reviews; these focused on delivery of AIT through the following routes: subcutaneous (SCIT; n = 3); sublingual (SLIT; n = 4); and both SCIT and SLIT (n = 2). This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity. The impact on measures of lung function or asthma control was however less clear. We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT. SLIT had a favorable safety profile when compared to SCIT, particularly in relation to the risk of systemic reactions. AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved. Bearing in mind the limitations of synthesizing evidence from systematic reviews and the fact that these reviews include mainly dated studies, a systematic review of current primary studies is now needed to update this evidence base, estimate the effectiveness of AIT on asthma outcomes and to investigate the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT.

Clinical practice guidelines are important tools to promote evidence-based clinical care, but not all countries have the capacity or infrastructure to develop these in-house. The European Academy of Allergy and Clinical Immunology has recently developed guidelines for the prevention, diagnosis and management of food allergy and the management of anaphylaxis. In order to inform dissemination, adaptation and implementation plans, we sought to identify countries that have/do not have national guidelines for food allergy and anaphylaxis. Two reviewers independently searched PubMed to identify countries with guidelines for food allergy and/or anaphylaxis from the inception of this database to December 2016. This was supplemented with a search of the Agency for Healthcare Research and Quality’s National Guideline Clearinghouse in order to identify any additional guidelines that may not have been reported in the peer-reviewed literature. Data were descriptively and narratively synthesized. Overall, 5/193 (3%) of countries had at least one guideline for food allergy or anaphylaxis. We found that one (1%) country had a national guideline for the prevention of food allergy, three (2%) countries had a guideline for the diagnosis of food allergy and three (2%) countries had a guideline for the management of food allergy. Three (2%) countries had an anaphylaxis guideline. This study concludes that the overwhelming majority of countries do not have any national clinical practice guidelines for food allergy or anaphylaxis.