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Purpose of Review: The purpose of this review is to provide a current overview on both primary and secondary measures of efficacy of therapeutic interventions for clinical trials in allergic rhinoconjunctivitis (ARC) patients. In particular, this review highlights similarities and differences regarding endpoints in trials involving allergen immunotherapy (AIT), pharmacotherapy and allergen avoidance and addresses unmet needs regarding these measures in the future., Recent Findings: In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) proposed a standard for the definition of the primary endpoint for AIT trials in ARC and, moreover, emphasized the advantages and disadvantages as well as unmet needs considering outcome measures for this treatment. Recently, as an (indirect) comparison of clinical efficacy of different interventions, the relative clinical impact (RCI) has been used to determine the percentage reduction of symptom scores in active versus placebo treatment., Summary: Several primary and secondary clinical endpoints of therapeutic interventions for clinical trials in ARC patients such as AIT or pharmacotherapy have been proposed by the U.S. Food and Drug Administration (FDA) as well as by the European Medicines Agency (EMA). Moreover, recommendations for the implication of these endpoints in clinical trials have been promoted by academia such as the World Allergy Organization (WAO) or the European Academy of Allergy and Clinical Immunology (EAACI).However, an urgent need for the future will be a thorough international harmonization regarding the definition of clinical endpoints, timing of assessments of clinical efficacy and determination of the clinically meaningful and relevant magnitude of efficacy of therapeutic interventions for clinical trials in ARC patients.

One hundred and ten years after Noon's first clinical report of the subcutaneous application of allergen extracts, allergen immunotherapy (AIT) has evolved as the most important pillar of the treatment of allergic patients. It is the only disease‐modifying treatment option available and the evidence for its clinical efficacy and safety is broad and undisputed. Throughout recent decades, more insights into the underlying mechanisms, in particular the modulation of innate and adaptive immune responses, have been described. AIT is acknowledged by worldwide regulatory authorities, and following the regulatory guidelines for product development, AIT products are subject to a rigorous evaluation before obtaining market authorization. Knowledge and practice are anchored in international guidelines, such as the recently published series of the European Academy of Allergy and Clinical Immunology (EAACI). Innovative approaches continue to be further developed with the focus on clinical improvement by, for example, the usage of adjuvants, peptides, recombinants, modification of allergens, new routes of administration, and the concomitant use of biologicals. In addition, real‐life data provide complementary and valuable information on the effectiveness and tolerability of this treatment option in the clinical routine. New mobile health technologies and big‐data approaches will improve daily treatment convenience, adherence, and efficacy of AIT. However, the current coronavirus disease 2019 (COVID‐19) pandemic has also had some implications for the feasibility and practicability of AIT. Taken together, AIT as the only disease‐modifying therapy in allergic diseases has been broadly investigated over the past 110 years laying the path for innovations and further improvement. [ABSTRACT FROM AUTHOR]

Abstract Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy. Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals’ quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits. We call upon Europe’s policy-makers to coordinate actions and improve individual and public health in allergy by: Promoting awareness of the effectiveness of allergen specific immunotherapy Updating national healthcare policies to support allergen specific immunotherapy Prioritising funding for allergen specific immunotherapy research Monitoring the macroeconomic and health economic parameters of allergy Reinforcing allergy teaching in medical disciplines and specialties The effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.

This ETR replaces the requirements for training in Allergology and Clinical Immunology as defined in Chapter 6 of the UEMS Charter on Training of Medical Specialist in the EU (2003). The complete version of the ETR can be found on the UEMS website.2 This ETR focuses on Allergology, since at European level our specialty has been recognized only as Allergology. To the Editor, The development of the European training requirements (ETR) for medical specialties in Europe is regulated by the Union Europeénne des Médecins Spécialistes (UEMS), a non-governmental organization representing national associations of medical specialists at European Level. [Extracted from the article]

Background: The effectiveness of allergen immunotherapy (AIT) in seasonal and perennial allergic rhinitis (AR) depends on the definition of pollen exposure intensity or time period. We recently evaluated pollen and symptom data from Germany to examine the new definitions of the European Academy of Allergy and Clinical Immunology (EAACI) on pollen season and peak pollen period start and end. Now, we aim to confirm the feasibility of these definitions to properly mirror symptom loads for grass and birch pollen‐induced allergic rhinitis in other European geographical areas such as Austria, Finland and France, and therefore their suitability for AIT and clinical practice support. Methods: Data from twenty‐three pollen monitoring stations from three countries in Europe and for 3 years (2014‐2016) were used to investigate the correlation between birch and grass pollen concentrations during the birch and grass pollen season defined via the EAACI criteria, and total nasal symptom and medication scores as reported with the aid of the patient's hay‐fever diary (PHD). In addition, we conducted a statistical analysis, together with a graphical investigation, to reveal correlations and dependencies between the studied parameters. Results: The analysis demonstrated that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to pollen‐induced symptom loads reported by PHD users during birch and grass pollen season. A statistically significant correlation (slightly higher for birch) has been found between the Total Nasal Symptom and Medication Score (TNSMS) and the pollen concentration levels. Moreover, the maximum symptom levels occurred mostly within the peak pollen periods (PPP) following the EAACI criteria. Conclusions: Based on our analyses, we confirm the validity of the EAACI definitions on pollen season for both birch and grass and for a variety of geographical locations for the four European countries (including Germany from a previous publication) analyzed so far. On this basis, the use of the EAACI definitions is supported in future clinical trials on AIT as well as in daily routine for optimal patient care. Further evaluation of the EAACI criteria in other European regions is recommended. [ABSTRACT FROM AUTHOR]

Keywords: allergen immunotherapy; allergy; asthma; subcutaneous immunotherapy; sublingual immunotherapy EN allergen immunotherapy allergy asthma subcutaneous immunotherapy sublingual immunotherapy 1070 1072 3 03/02/22 20220301 NES 220301 Allergen immunotherapy (AIT) has gained a permanent place in the therapeutic arsenal for the patient with allergic rhinitis. Provided the diagnosis of asthma is correct, and the specific allergy is present, and a therapeutic extract containing the relevant allergen components is used, then AIT may result in clinical improvement of asthma. The recent EAACI guideline about HDM driven asthma recommends AIT as an add-on to regular asthma therapy for adults with controlled or partially controlled allergic asthma. Allergen immunotherapy, allergy, asthma, subcutaneous immunotherapy, sublingual immunotherapy. [Extracted from the article]

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention. [ABSTRACT FROM AUTHOR]

To cite this article: Röder E, Berger MY, Hop WCJ, de Groot H, Gerth van Wijk R. The relevance of patient-reported outcomes in a grass pollen immunotherapy trial in children and adolescents with rhinoconjunctivitis. Pediatr Allergy Immunol 2012. Abstract Background: Patient-reported outcomes (PROs) are the only instruments available to assess the efficacy of an intervention in patients with allergic rhinoconjunctivitis. As allergic rhinoconjunctivitis is a systemic disease, it is now recommended to use not only PROs focusing at classical symptoms, but also health-related quality of life (HRQL) instruments in immunotherapy trials. Methods: A previously published immunotherapy trial in children and adolescents (6-18 yr) with hay fever provided us with data to assess the relevance of two of these additional outcome measures, the disease-specific rhinoconjunctivitis quality of life questionnaire (RQLQ) and the generic COOP/WONCA-charts (CWC). A PRO was considered relevant if it was responsive to pollen exposure and at least had a moderate correlation with the classical symptoms of allergic rhinoconjunctivitis. Furthermore, we evaluated a post-season PRO, that is, a global assessment of symptoms (GAS). This assessment is used in clinical trials as a tool for selecting participants with sufficient symptoms and in daily practice to evaluate the patient's complaints during the preceding season. We assessed the correlation of this retrospective score with the actual symptoms during the previous pollen season. Results: Data from 36 children and 63 adolescents were analysed. On the basis of the total scores of the paediatric and adolescent version of the RQLQ, both questionnaires were considered relevant as they were responsive to exposure and showed a moderate to strong correlation with the rhinoconjunctivitis symptoms. However, in both children and adolescents, 40% of the RQLQ items were not relevant according to our definition. The CWC as a whole and the separate charts appear less relevant because of the weak correlations with the daily symptom score from the diary. The correlation between our post-season GAS and the in season daily symptom score was weak. Conclusion: The paediatric and adolescent RQLQ are relevant, but could be shortened as they contain a substantial number of irrelevant items. The CWC are not relevant in the monitoring of children and adolescents with allergic rhinoconjunctivitis caused by grass pollen. The retrospective GAS does not sufficiently reflect the actual symptoms during the preceding season. [ABSTRACT FROM AUTHOR]

To cite this article: de Bot CMA, Moed H, Berger MY, Röder E, Hop WCJ, de Groot H, de Jongste JC, van Wijk RG, Bindels PJE, van der Wouden JC. Sublingual immunotherapy not effective in house dust mite-allergic children in primary care. Pediatr Allergy Immunol 2011; Doi: 10.1111/j.1399-3038.2011.01219.x Abstract Background: Sublingual immunotherapy (SLIT) as a therapy for the treatment of allergic rhinitis in children might be acceptable as an alternative for subcutaneous immunotherapy. However, the efficacy of SLIT with house dust mite extract is not well established. Objective: To investigate whether SLIT in house dust mite-allergic children recruited in primary care is effective and safe. Methods: Children aged 6-18 years (n = 251) recruited in primary care with a house dust mite-induced allergic rhinitis received either SLIT or placebo for 2 years. Symptoms and medication use were assessed throughout the study. Primary outcome parameter was the mean total nose symptom score (scales 0-12) during the autumn of the second treatment year. Safety was assessed by recording any adverse event. Results: Overall, the mean nose symptom score ± s.d. after 2 years of treatment showed no significant effect of SLIT (symptom score intervention group 2.26 ± 1.84 vs. placebo group, 2.02 ± 1.67; p = 0.08). There were no significant differences in secondary outcomes, nor in subgroup analyses. The number of patients reporting adverse events was comparable between both groups. Conclusions: Sublingual immunotherapy with house dust mite allergen was not better than placebo in reducing rhinitis symptoms in house dust mite-allergic children in primary care. SLIT as administered in this study can be considered safe. [ABSTRACT FROM AUTHOR]

Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. Objective: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. Methods: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. Results: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: −0.08, 95%CI, −0.66-0.50; P = .78). No differences were found for rescue medication–free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P = .001). Conclusion: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. Clinical implications: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy. [Copyright &y& Elsevier]