Shifts in allergy practice in a COVID-19 world: Implications of pre-COVID-19 national health care provider and patient surveys of treatments for nasal allergies.

Background: Most U.S. patient and health care provider surveys with regard to nasal allergy treatments were conducted before sublingual immunotherapy (SLIT)-tablets and allergy immunotherapy (AIT) shared decision-making tools were available. Objective: Patient and health care provider surveys with regard to current perceptions of nasal allergy burden, symptoms, and treatments were conducted to compare with previous surveys and provide insight into the use of SLIT-tablets and AIT shared decision-making tools. Methods: From November-December 2019, adults (N = 510) diagnosed with nasal allergies and health care providers (N = 304) who treated nasal allergies in the United States completed surveys with regard to nasal allergy management. Results: Of the patient respondents, 42% reported that their symptoms were only somewhat controlled and 48% had avoided activities because of their nasal allergies. In all, 38% were using only over-the-counter (OTC) medications for treatment, and 42%, 7%, and 8% had ever received subcutaneous immunotherapy (SCIT), sublingual allergy drops, or SLIT-tablets, respectively; 56% and 85% reported that they had never discussed SCIT or SLIT, respectively, with their health care provider. Of the health care provider respondents, 45%, 58%, and 20% were very likely to discuss OTC medications, SCIT, or SLIT, respectively. Allergists were more inclined to discuss SCIT with their patients than other health care providers (82% versus 33%, respectively). Most allergists (67%) and other health care providers (62%) reported that they did not use an AIT shared decision-making tool, primarily because of unawareness. Conclusion: The patients with nasal allergies continued to report inadequate symptom control and activity impairment. SLIT-tablets and AIT shared decision-making tools were underused. In the coronavirus disease 2019 era, social distancing may limit office visits, which impacts SCIT administration and prompts increased use of telemedicine and a possible advantage for at-home-administered SLIT-tablets over SCIT.

Consensus report from the Food Allergy Research & Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit.

Food allergy is a major health problem affecting 5% to 10% of the population in developed nations, including an estimated 32 million Americans. Despite the large number of patients suffering from food allergies, up until the end of January 2020, no treatment for food allergies had been approved by the US Food and Drug Administration. The only options were avoidance of food allergen triggers and acute management of allergic reactions. A considerable body of data exists supporting oral immunotherapy (OIT) as a promising, novel treatment option, including that for the now Food and Drug Administration-approved peanut OIT product Palforzia (Aimmune Therapeutics, Brisbane, Calif). However, data for long-term quality-of-life improvement with OIT varies, depending on the measures used for analysis. Like many therapies, OIT is not without potential harms, and burdens, and the evaluation of patient-specific risk-benefit ratio of food OIT produces challenges for clinicians and patients alike, with many unanswered questions. Food Allergy Research & Education organized the Oral Immunotherapy for Food Allergy Summit on November 6, 2019, modeled after the PRACTALL sessions between the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology to address these critical issues. Health care providers, patient representatives, researchers, regulators, and food allergy advocates came together to discuss OIT and identify areas of common ground as well as gaps in existing research and areas of uncertainty and disagreement. The purpose of this article was to summarize that discussion and facilitate collaboration among clinicians and patients to help them make better-informed decisions about offering and accepting OIT, respectively, as a therapeutic option.

Allergy immunotherapy: Future directions for the 2020s.

Allergy immunotherapy (AIT), whether administered as subcutaneous immunotherapy or as sublingual immunotherapy (SLIT), is an effective treatment for sensitization to inhalant allergens. There remain, however, some important unresolved issues, such as the need for compelling evidence for or against the efficacy of treatment with multiple unrelated allergen extracts and optimal dosing with SLIT-liquid preparations. Both methods of AIT involve prolonged periods of treatment to achieve persisting benefit. This can be inconvenient and expensive, and failure to complete the period of prescribed treatment is common with both methods. New approaches are being developed and studied to make AIT more effective, safer, or more convenient. Among these approaches are using alternative routes of administration; using adjuvants, including vitamin D, Toll-like receptor ligand agonists, biologics, or probiotics; introducing additional SLIT tablets; defining the patterns of major and minor allergen sensitivity of patients and the content of allergen extracts to better match sensitization with treatment; and treating cats to reduce their allergen release. The allergen molecules themselves are being altered to make them less reactive with specific immunoglobulin E, both by creating allergoids and by using recombinant technology to produce modified allergen molecules. Which, if any, of these new approaches will become part of AIT practice in the next decade depends in part on their efficacy and in part on the availability of the resources to adequately study them.

Advances in the approach to the patient with food allergy.

Advances in food allergy diagnosis, management, prevention, and therapeutic interventions have been significant over the past 2 decades. Evidence-based national and international guidelines have streamlined food allergy diagnosis and management, whereas paradigm-shifting work in primary prevention of peanut allergy has resulted in significant modifications in the approach to early food introduction in infants and toddlers. Innovative investigation of food allergy epidemiology, systems biology, effect, and management has provided important insights. Although active therapeutic approaches to food allergy remain experimental, progress toward licensed therapies has been substantial. Mechanistic understanding of the immunologic processes underlying food allergy and immunotherapy will inform the future design of therapeutic approaches targeting the food-induced allergic response. Global strategies to mitigate the substantial medical, economic, and psychosocial burden of food allergy in affected subjects and families will require engagement of stakeholders across multiple sectors in research, health care, public health, government, educational institutions, and industry. However, the relationship between the well-informed allergy care provider and the patient and family remains fundamental for optimizing the care of the patient with food allergy.

Recent developments and highlights in rhinitis and allergen immunotherapy.

This review paper aims to provide an overview of recent developments in the field of allergic and non-allergic rhinitis, as well as allergen immunotherapy. Recent advances in phenotyping and endotyping various forms of rhinitis have brought us one step closer towards tailoring treatment more appropriately for a given patient. Updates on local allergic rhinitis are also covered. Allergen immunotherapy (AIT) is an area of significant interest, with multiple original papers and recent position papers and guidelines published. Evidence related to the application of AIT in seasonal and perennial allergic rhinitis (AR), local allergic rhinitis and novel and expanded applications is discussed in the publication.

Recent developments and highlights in allergen immunotherapy.

Allergen immunotherapy (AIT) is the only disease-modifying treatment option for patients with IgE-mediated inhalant allergies. Though used in clinical practice for more than 100 years, most innovations in AIT efficacy and safety have been developed in the last two decades. This expert review aimed to highlight the recent progress in AIT for both application routes, the sublingual (SLIT) and subcutaneous (SCIT) forms. As such, it covers recent aspects regarding efficacy and safety in clinical trials and real-life data and outlines new concepts in consensus and position papers as well as in guidelines for AIT. Potential clinical and nonclinical biomarkers are discussed. This review also focuses on potential future perspectives in AIT, such as alternative application routes, immune-modulating adjuvants, and recombinant vaccines. In conclusion, this state of the art review provides a comprehensive overview of AIT and highlights unmet needs for the future.

Perspectives in allergen immunotherapy: 2017 and beyond.

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.

Current insights in allergen immunotherapy.

OBJECTIVE: Allergen-specific immunotherapy (AIT) in its subcutaneous and sublingual forms is currently a well-established and experimentally supported treatment for respiratory allergy and hymenoptera venom allergy. There have been advances in its use linked strictly to the advancement in the knowledge of the molecular mechanisms of allergy, the production of well-characterized extracts, and diagnostic techniques. The use of AIT in asthma and the application of new approaches are expanding. We briefly review the advances and concerns in the use of AIT. DATA SOURCES: PubMed and Scopus. STUDY SELECTIONS: The most recent and clinically relevant literature was selected and reviewed. RESULTS: The introduction of high-quality products supported by large dose-finding trials has yielded better defined indications, contraindications, and modalities of use. Some specific products in tablet form have recently been approved in the United States. Sublingual immunotherapy has been found to be effective in asthma, which until recently had been a matter of debate. Another promising therapy is oral and sublingual desensitization for food allergy, for which encouraging results have recently been reported. In the near future, other options will be available, including new routes of administration (intralymphatic and epicutaneous), allergoids, engineered allergens, and peptides. The use of component-resolved diagnosis techniques will further refine and target AIT prescriptions. CONCLUSION: This condensed and updated review shows that AIT remains a viable treatment option, especially after the introduction of standardized tablets for some allergens. Food allergy and new administration routes represent a promising expansion.

Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance.

Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation, and reporting have developed significantly. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety, and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike. Those standards should be followed today, and products answering to them should be preferred over others lacking optimization and proof of efficacy and safety. Molecular and cellular mechanisms of AIT include early mast cell and basophil desensitization effects, regulation of T- and B-cell responses, regulation of IgE and IgG4 production, and inhibition of responses from eosinophils, mast cells, and basophils in the affected tissues. There were many developments to improve vaccination strategies, demonstration of new molecules involved in molecular mechanisms, and demonstration of new biomarkers for AIT during the last few years. The combination of probiotics, vitamins, and biological agents with AIT is highlighting current advances. Development of allergoids and recombinant and hypoallergenic vaccines to skew the immune response from IgE to IgG4 and regulation of dendritic cell, mast cell, basophil, innate lymphoid cell, T-cell, and B-cell responses to allergens are also discussed in detail.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Immunological mechanisms of allergen-specific immunotherapy.

Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.

Analysis of allergic immune responses in humanized mice.

Nowadays, more than 25% of the population in industrial countries are affected by IgE-mediated (atopic) allergic diseases such as allergic rhinitis, asthma and atopic eczema. Due to intensive research on basis of in vitro studies with human immune cells and different murine in vivo models of allergy fundamental mechanisms of allergic immune responses have been elucidated during the last years. However, human studies are restricted and the immune system of mice differs from the human immune system in several aspects so that the transferability of experimental results from mice to men is limited. Humanized mice represent a new tool to analyze the interaction of human immune cells under physiological conditions as far as possible, particularly to test novel therapeutic strategies. This review summarizes the impact of humanized mouse models for the investigation and treatment of allergic diseases.

The Heterogeneity of Oral Immunotherapy Clinical Trials: Implications and Future Directions.

Food allergy is a potentially life-threatening disease which affects up to 8% of children and 2-3% of adults. Increasing food allergy prevalence poses a major public health concern. Induction of desensitization to food allergens through oral immunotherapy (OIT) is an expanding area of study encompassing peanut, egg, milk, and other food allergens. OIT consists of administering incremental doses of food allergen to food-allergic patients, to induce a state of desensitization. Safety, tolerability, and efficacy all remain ongoing concerns. Clinical trials for oral immunotherapy have encompassed many variations, including differences in dosage sizes and frequency, duration of build-up, type of allergen used, patient characteristics, and adjuvant therapies. Consequently, studies have also shown variation in rates of adverse effects, and successful desensitization. Here, we provide an overview of the key studies and discuss the implications of this heterogeneity. While desensitization is successful in the majority of patients, only a minority appear to develop sustained unresponsiveness even after years of therapy. Much larger and longitudinal studies using more homogenous protocols are needed in order to evaluate the clinical applicability of OIT, its long-term effectiveness, and effect on quality of life. The role of adjunctive therapies, including omalizumab and probiotics, requires further evaluation.

Oral Immunotherapy for Food Allergies.

Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice.

[Innovative immunotherapies of respiratory allergic diseases]. / Immunothérapies innovantes des maladies allergiques respiratoires.

Allergen immunotherapy (AIT) is an effective method in the treatment of respiratory allergic diseases (asthma, rhinitis and conjunctivitis). In addition to reducing symptoms, AIT can alter the course of allergic disease and remains efficient long after it has been discontinued by inducing specific tolerance to the allergen. In current clinical practice, immunotherapy is administered by subcutaneous or sublingual routes. The duration of efficacy is 7 to 12 years. It can prevent the development of both asthma and sensitization to new allergens. Despite recent progresses, other approaches are needed, especially for allergies (atopic dermatitis, food allergies). The new AIT improvement approaches involve the use of adjuvants or recombinant allergies, peptides and new routes of administration.

New developments in allergen immunotherapy.

PURPOSE OF REVIEW: Allergic rhinitis, conjunctivitis, and asthma impact quality of life and cost billions of dollars in lost wages, productivity, and medical expenditures. Allergen immunotherapy is the only therapy that alters the allergen immune response, resulting in fewer symptoms upon natural exposure. This review summarizes recent immunotherapy developments. RECENT FINDINGS: Subcutaneous immunotherapy (SCIT) remains a disease modifying treatment for allergic rhinoconjunctivitis and asthma with rare complications of therapy. Recent evidence suggests that SCIT may be effective in select cases of atopic dermatitis, particularly for patients with dust mite sensitivity. Sublingual immunotherapy (SLIT) tablets are now commercially available for grass and ragweed allergy and appear to have a superior safety profile to SCIT with similar long-term effectiveness, because as with SCIT, symptom improvement persists after the SLIT course is completed. SLIT tablets are administered daily at home (after initial supervised dosing) and may be used shortly before and during the target pollen seasons in a precoseasonal fashion (instead of perennial dosing). Research continues into experimental approaches using oral food allergen immunotherapy (OIT) to modify the natural history of food allergies. Although a proportion of patients in OIT trials experience sustained unresponsiveness, many do not and current recommendations limit the use of OIT to research protocols. SUMMARY: Patients have new well tolerated and effective options for more convenient treatment of asthma and allergic rhinoconjunctivitis associated with grass and ragweed allergy. SCIT remains effective for polysensitized patients and may be an option for some patients with atopic dermatitis. Research continues into novel food allergy treatments.

The future of antigen-specific immunotherapy of allergy.

More than 25% of the population in industrialized countries suffers from immunoglobulin-E-mediated allergies. The antigen-specific immunotherapy that is in use at present involves the administration of allergen extracts to patients with the aim to cure allergic symptoms. However, the risk of therapy-induced side effects limits its broad application. Recent work indicates that the epitope complexity of natural allergen extracts can be recreated using recombinant allergens, and hypoallergenic derivatives of these can be engineered to increase treatment safety. It is proposed that these modified molecules will improve the current practice of specific immunotherapy and form a basis for prophylactic vaccination.

The oral food desensitization in the Italian allergy centres.

BACKGROUND: Attempts aimed at inducing food tolerance through oral food desensitization (OFD) for the treatment of IgE-mediated food allergies are increasing. In Italy, a number of allergy centres offer this procedure. OBJECTIVE: To collect information on how these centres are organized, how patients are selected, the methods used to administer OFD and how adverse reactions are managed. METHODS: A questionnaire was e-mailed to all the Italian allergy centres offering OFD. RESULTS: The survey shows a high degree of variability between centres. A correct diagnosis of food allergy is crucial for selecting patients for OFD. In the Italian allergy centres, oral food challenges are mostly open label (84%), but in 16% of cases they are single-blind (8%) or double-blind (8%). A high proportion of allergy centres (83%) offer OFD to children presenting forms of anaphylaxis triggered by traces--or very low doses--of food allergen. The majority of allergy centres (76%) enroll patients over 3 years of age, with 44% enrolling patients above the age of 5. Not-controlled asthma, unreliability of parents in the management of OFD and/or risk of adverse events, are the main reasons for exclusion from the procedure. CONCLUSION: Although OFD may sometimes be successful and may be considered a valid alternative to an elimination diet, further randomized controlled trials are needed, in order to clarify some controversial points, such as the characteristics of the child undergoing OFD, and the methods of food preparation and administration. Moreover, further studies should further investigate OFD safety, efficacy and costs.

[Allergen specific immunotherapy for rhinitis allergica : New applications]. / Allergenspezifische Immuntherapie bei Rhinitis allergica : Neue Applikationsformen.

BACKGROUND: Allergic diseases are among the most common diseases of humans. The immune response towards allergens is regulated by T-lymphozytes and characterized by an interleukin (IL)-4, IL-5 and IL-13 dominated Th2 cytokine profile. RESULTS: Allergen-specific immunotherapy (AIT) is the only causative treatment option and able to change the course of disease, e. g. to prevent the development of asthma and new sensitizations. The intralymphatic delivery of allergenes named intralymphatic immunotherapy (ILIT) has been evaluated in clinical trials and was demonstrated to be a highly potent application route with low effort and side effects while having equal efficacy if compared with current standard AIT forms. However, studies that verify important questions like optimal dose, new allergen forms, use of adjuvants etc. are still missing. Moreover, it has to be evaluated, whether different indications like rhinitis, or atopic dermatitis are suitable for ILIT and whether it is useful in children. Epicutaneous immunotherapy (EPIT) is a possible alternative application form. It is minimally invasive and basically consists of the affixation of allergen containing patches to the epidermis over 6 weeks. From the studies performed so far, the authors concluded, that epicutaneous immunotherapy is safe and efficacious in a dose-dependent manner after 6 patches only. CONCLUSIONS: AIT is accepted to be the only causative treatment option for allergies. New application routes in ILIT and EPIT may become more important and allow for different delivery methods in the future, however further clinical studies are required and in preparation.

Video Q&A: allergies and allergen immunotherapy--an interview with Alfred William Frankland.

In this video Q&A, we talk to Dr Alfred William Frankland about the highlights of his career, including working alongside Sir Alexander Fleming, co-founding the British Allergy Society, and introducing pollen counts to UK weather forecasts. We also discuss his opinions on why misconceptions about allergies and allergen immunotherapy still exist. Please see related article: http://www.biomedcentral.com/1741-7015/11/255.