Aim and scopePediatric Allergy and Immunology publishes original contributions and comprehensive reviews related to the understanding and treatment of immune defi ciency, allergic infl ammatory and infectious diseases in children. Other areas of interest include development of specifi c and accessory immunity, and the immunological interaction during pregnancy and lactation between mother and child. As the journal is intended to promote communication between scientists engaged in basic research and clinicians working with children, both clinical and experimental work will be published.

blind placebo controlled; EAACI, European Academy of Allergy and Clinical Immunology; FEF 25-75, forced expiratory flow at 25-75% of the pulmonary volume; FEV1, forced expiratory volume in 1 second; GINA, Global Initiative for Asthma; GRADE, The Grading of Recommendations Assessment, Development and Evaluation; HCP, healthcare professional; HDM, house dust mites; ICS, inhaled corticosteroids; MEF 25, maximal expiratory flow at 25% of forced vital capacity; MEF 50, maximal expiratory flow at 50% of forced vital capacity; MEF 75, maximal expiratory flow at 75% of forced vital capacity; PD20, provocative dose causing a 20% drop in FEV1; QoL, quality of life; RCTs, randomized control trials; ROB, risk of bias; SCIT, subcutaneous allergen immunotherapy; SLIT, sublingual allergen immunotherapy; SmPC, Summary of product characteristics; WAO, World Allergy Organization; WHO, World Health Organization.Agache and Lau are joint first co-authorship. External peer-reviewers: AbstractAllergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AITwith HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence). K E Y W O R D Sallergen immunotherapy, allergy, asthma, asthma control, asthma exacerbations, GRADE, house dust mites, lung function

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.

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Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products.While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration. K E Y W O R D Sallergen immunotherapy, allergic diseases, allergy, regulation | INTRODUCTIONThe availability of medicinal products to provide a reliable diagnosis of clinical allergy and effective treatment(s) is of critical importance for patients with suspected or proven allergy. Products for allergen immunotherapy (AIT) have been approved by national competent authorities in different regions of the world. However, the regulatory landscape governing the approval of these products is enormously heterogeneous-both within the European Union (EU) and even more so when looking globally-thereby rendering it extremely complicated and challenging to develop a harmonized, international approach to regulating these products.Pharmaceutical companies are increasingly focused on global strategies to develop and market their products. It is therefore very important to understand the current regulatory situation for allergen products from an international perspective, as this will have a direct impact on the availability of these medicinal products to patients throughout the world. Certain regulatory patterns can be observed on a global scale. For example, whereas AIT was previously mainly used and placed on the market on the basis of expert opinions with limited regulatory oversight, the requirements for high-quality clinical data for granting market access have greatly increased during the last 20 years. In the EU, legislation applicable for new and existing products 1,2 has been in force since 1989 demanding that allergen products are registered as medicinal products with corresponding requirements for clinical data. The development of the guid...