Does evidence support the use of cat allergen immunotherapy?

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Erratum to: Allergen immunotherapy for allergic rhinoconjunctivitis: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0099-6.].

Erratum to: Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0095-x.].

Erratum to: Allergen immunotherapy for IgE-mediated food allergy: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0113-z.].

Erratum to: Allergen immunotherapy for allergic asthma: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0094-y.].

EAACI guidelines on allergen immunotherapy: Prevention of allergy.

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post-AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease-modifying treatment exists but there is an urgent need for more high-quality clinical trials.

Idiopathic Anaphylaxis.

Idiopathic anaphylaxis is a rare life-threatening disorder with symptoms similar to other forms of anaphylaxis. There is lack of a robust evidence base underpinning the treatment of anaphylaxis and even less so for idiopathic anaphylaxis. Much of the evidence therefore comes from relatively small case series and expert opinion. Idiopathic anaphylaxis is a diagnosis of exclusion, requiring a thorough history and careful diagnostic work-up investigating possible triggers and underlying predisposing factors. Key diagnostic tests include skin-prick testing, tests for specific-IgE, component-resolved diagnostics, and in some cases for allergen challenge tests. Other recognized causes of anaphylaxis, such as foods, medications, insect stings, latex, and exercise, should all be considered, as should differential diagnoses such as asthma. While the cause of idiopathic anaphylaxis remains unknown, prompt treatment with intramuscular epinephrine (adrenaline) administered into the anterolateral aspect of the thigh is associated with good prognosis. There may also be a role for H1-antihistamines and corticosteroids as second-line agents. Patients need to be carefully monitored for signs of deterioration and/or a possible protracted or biphasic reaction. Patients with frequent episodes of anaphylaxis (e.g., six or more episodes/year) should be considered for preventive therapy, which may include corticosteroids, H1- and H2-antihistamines, and, in some cases, mast cell stabilizers such as ketotifen. Alternative immune-suppressants (e.g., methotrexate) and anti-IgE may rarely also need to be considered. In many cases, the frequency of anaphylaxis declines such that regular use of corticosteroids can be discontinued after 9-12 months. Pediatric patients should be treated with similar regimens as adults, but with appropriate dose adjustments. Patients should carry their self-injectable epinephrine and other emergency medications at all times in order to deal with emergency situations.

Allergen immunotherapy for allergic asthma: a systematic overview of systematic reviews.

BACKGROUND: There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma. OBJECTIVES: To undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

National clinical practice guidelines for food allergy and anaphylaxis: an international assessment.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study concludes that the overwhelming majority of countries do not have any national clinical practice guidelines for food allergy or anaphylaxis.

Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Anaphylaxis: epidemiology, aetiology and relevance for the clinic.

INTRODUCTION: Anaphylaxis is responsible for considerable morbidity and may in some cases prove fatal. Areas covered: This review summarises the findings from recent studies on the epidemiology and aetiology of anaphylaxis and draws on the insights from this work and recent international guidelines to consider the implications for clinical care. Acute management of anaphylaxis is centred on early recognition, treatment with adrenaline (epinephrine) and other essential life-support measures. The importance of longer-term care of patients with a history of or at risk of anaphylaxis are also considered with a view to minimising the risk of further reactions. Tailored individual anaphylaxis management plans should be a routine component of this longer-term care with provision of adrenaline auto-injectors to those at risk of further episodes of anaphylaxis. More generally, there is a need to ensure that there are standard protocols in place to ensure that risks of triggering anaphylaxis are minimised and appropriate acute and long-term care are provided if reactions occur. Expert commentary: It is important to be aware that anaphylaxis may occur in patients of any age, sex or ethnicity. Early recognition and prompt treatment with adrenaline are potentially life-saving. Careful assessment of risk and appropriate long-term management are key to improving long-term outcomes in those at risk of repeat episodes of anaphylaxis.

Quality indicators for the acute and long-term management of anaphylaxis: a systematic review.

BACKGROUND: The quality of acute and long-term anaphylaxis management is variable and this contributes to the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes, but implementing guideline recommendations in routine practice is challenging. Quality indicators have the potential to support guideline implementation efforts. OBJECTIVE: To identify quality indicators to support the acute and long-term management of anaphylaxis. METHODS: We conducted a systematic review of the literature that involved searching Medline, EMBASE and CINAHL databases for peer-reviewed published literature for the period 1 January 2005-31 December 2015. Additionally we searched Google for grey and unpublished literature. The identified indicators were descriptively summarized against the most recent international anaphylaxis guidelines (i.e. those produced by the European Academy of Allergy and Clinical Immunology) and critically evaluated using the Agency for Healthcare Research and Quality's criteria for indicator development. RESULTS: Our searches revealed 830 publications, from which we identified five sources for 54 indicators addressing both acute (n = 27) and long-term (n = 27) management of anaphylaxis. The majority of indicators were developed through expert consensus with relatively few of these having been formally piloted or tested to demonstrate that they could discriminate between variations in practice and/or that they were sensitive to change. CONCLUSIONS: There is a need for a comprehensive set of quality indicators for anaphylaxis management. We have however identified some indicators for the acute and long-term management of anaphylaxis that could with relatively little additional work support efforts to translate guideline recommendations into clinical care.

Allergen immunotherapy for the prevention of allergy: A systematic review and meta-analysis.

BACKGROUND: There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease. METHODS: Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses. RESULTS: A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile. CONCLUSIONS: AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT.

Allergen immunotherapy for IgE-mediated food allergy: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated food allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in IgE-mediated food allergy. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.